diff --git a/CITATION.cff b/CITATION.cff
index 010c6fdf..6c888a7f 100644
--- a/CITATION.cff
+++ b/CITATION.cff
@@ -1,6 +1,6 @@
title: STRchive
-version: 2.8.0
-date-released: "2025-08-08"
+version: 2.9.0
+date-released: "2025-08-12"
url: https://github.com/dashnowlab/STRchive
authors:
- family-names: Dashnow
diff --git a/data/STRchive-citations.json b/data/STRchive-citations.json
index 6a6e783f..e2140641 100644
--- a/data/STRchive-citations.json
+++ b/data/STRchive-citations.json
@@ -130646,20064 +130646,22176 @@
"note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: url:https://gnomad.broadinstitute.org/short-tandem-repeat/XYLT1?dataset=gnomad_r4"
},
{
- "id": "omim:309548",
- "manubot_success": false,
- "link": "https://omim.org/entry/309548",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/309548. Skipping"
+ "id": "doi:10.1016/j.omsc.2023.100340",
+ "manubot_success": true,
+ "title": "Treatment of the median mandibular cleft in Richieri-Costa-Pereira syndrome with a customized total mandibular prosthesis: A case report",
+ "type": "article-journal",
+ "doi": "10.1016/j.omsc.2023.100340",
+ "authors": [
+ ["Ryuichi", "Hoshi"],
+ ["Paula", "Marcella Silva Drago"],
+ ["Henrique", "Mascarenhas Villela"],
+ ["Gabriela", "Gayer Sheibler"],
+ ["Daniel", "Serra Cassano"],
+ ["Fernanda", "Barros Silva de Pedreira Barbosa"],
+ ["Lissa", "Hoshi"],
+ ["Isadora", "dos Santos Lima"]
+ ],
+ "publisher": "Oral and Maxillofacial Surgery Cases",
+ "issn": "",
+ "date": "2024-03-01",
+ "link": "https://doi.org/g8rxvs",
+ "abstract": "",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: doi:10.1016/j.omsc.2023.100340"
+},
+{
+ "id": "genereviews:NBK1487",
+ "manubot_success": true,
+ "link": "http://www.ncbi.nlm.nih.gov/books/NBK1487/",
+ "title": "COMP-Related Pseudoachondroplasia",
+ "type": "chapter",
+ "doi": "",
+ "authors": [
+ ["Michael D.", "Briggs"],
+ ["Michael J.", "Wright"]
+ ],
+ "publisher": "GeneReviews\u00ae",
+ "issn": "",
+ "date": "1993-01-01",
+ "abstract": "COMP-related pseudoachondroplasia (COMP-PSACH) is characterized by normal length at birth and normal facies. Often the presenting feature is a waddling gait, recognized at the onset of walking. Typically, the growth rate falls below the standard growth curve by approximately age two years, leading to a moderately severe form of disproportionate short-limb short stature. Joint pain during childhood, particularly in the large joints of the lower extremities, is common. Degenerative joint disease is progressive; approximately 50% of individuals with COMP-PSACH eventually require hip replacement surgery., The diagnosis of COMP-PSACH can be made on the basis of clinical findings and radiographic features. Identification of a heterozygous pathogenic variant in COMP on molecular genetic testing establishes the diagnosis if clinical features are inconclusive., Treatment of manifestations: Analgesics for joint pain; encourage physical activities that do not cause excessive wear and/or damage to the joints; osteotomy for lower limb malalignment; rarely, surgery for scoliosis; C1-C2 fixation for symptoms and radiographic evidence of cervical spine instability; attention to and social support for psychosocial issues related to short stature for affected individuals and their families. Surveillance: Assess growth at each visit throughout childhood. Regular examinations for evidence of symptomatic joint hypermobility and/or lower limb malalignment, kyphoscoliosis, degenerative joint disease, and neurologic manifestations, particularly spinal cord compression secondary to odontoid hypoplasia. Assess for psychosocial issues annually or at each visit. Agents/circumstances to avoid: In those with odontoid hypoplasia, extreme neck flexion and extension should be avoided., COMP-PSACH is inherited in an autosomal dominant manner. Some individuals diagnosed with COMP-PSACH have an affected parent. A proband diagnosed with COMP-PSACH may have the disorder as the result of a de novo pathogenic variant. Each child of an individual with COMP-PSACH and a reproductive partner with normal bone growth has a 50% chance of inheriting the COMP pathogenic variant and having COMP-PSACH. Because many individuals with short stature select reproductive partners with short stature, offspring of individuals with COMP-PSACH may be at risk of having double heterozygosity for two dominantly inherited bone growth disorders. Once the COMP pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.",
+ "language": "eng",
+ "note": "PMID: 20301660\nThis CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: url:https://www.ncbi.nlm.nih.gov/books/NBK1487"
+},
+{
+ "id": "genereviews:NBK541729",
+ "manubot_success": true,
+ "link": "http://www.ncbi.nlm.nih.gov/books/NBK541729/",
+ "title": "Spinocerebellar Ataxia Type 37",
+ "type": "chapter",
+ "doi": "",
+ "authors": [
+ ["Antoni", "Matilla-Due\u00f1as"],
+ ["Victor", "Volpini"]
+ ],
+ "publisher": "GeneReviews\u00ae",
+ "issn": "",
+ "date": "1993-01-01",
+ "abstract": "Spinocerebellar ataxia type 37 (SCA37) is characterized by adult onset, dysarthria, slowly progressive gait and limb ataxia with severe dysmetria in the lower extremities, mild dysmetria in the upper extremities, dysphagia, and abnormal ocular movements (dysmetric vertical saccades, irregular and slow vertical smooth pursuit, slow vertical optokinetic nystagmus, and oscillopsia (visual disturbance in which objects appear to oscillate). In most individuals, the initial signs/symptoms include falls, dysarthria, or clumsiness followed by a complete cerebellar syndrome. A distinctive clinical feature is the presence of altered vertical eye movements in early stages of the disease, even preceding ataxia symptoms. Clinical progression is slow and affected individuals usually become wheelchair bound between ten and 33 years after disease onset., The diagnosis of SCA37 is established in a proband by identification of a heterozygous ATTTC repeat insertion within DAB1 by molecular genetic testing. All affected persons have 31-75 ATTTC repeats, flanked on both sides by polymorphic ATTTT repeats over 58 units., Treatment of manifestations: Currently, no treatment reverts the course of the disease. Speech therapy to improve communication and ameliorate dysphagia; thickness modification of food and fluids to prevent aspiration; physical therapy to train balance; use of external devices (e.g., canes or walkers) when needed to avoid falls; occupational/behavioral therapy. Surveillance: Scale for the Assessment and Rating of Ataxia (SARA) score annually; electrooculographic tests may be performed every two years (cooperation required); brain MRI volumetry every two years., SCA37 is inherited in an autosomal dominant manner. All individuals diagnosed to date with SCA37 have an affected parent. Each child of an individual with SCA37 is at a 50% risk of inheriting the intronic ATTTC repeat insertion within DAB1. Prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible if the ATTTC repeat insertion within DAB1 has been identified in an affected family member.",
+ "language": "eng",
+ "note": "PMID: 31145571\nThis CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: url:https://www.ncbi.nlm.nih.gov/books/NBK541729"
+},
+{
+ "id": "genereviews:NBK1529",
+ "manubot_success": true,
+ "link": "http://www.ncbi.nlm.nih.gov/books/NBK1529/",
+ "title": "Huntington Disease-Like 2",
+ "type": "chapter",
+ "doi": "",
+ "authors": [
+ ["David G.", "Anderson"],
+ ["Amanda", "Krause"],
+ ["Russell L.", "Margolis"]
+ ],
+ "publisher": "GeneReviews\u00ae",
+ "issn": "",
+ "date": "1993-01-01",
+ "abstract": "Huntington disease-like 2 (HDL2) typically presents in midlife with a relentless progressive triad of movement, emotional, and cognitive abnormalities that lead to death within ten to 20 years. HDL2 cannot be differentiated from Huntington disease (HD) clinically. Neurologic abnormalities include chorea, hypokinesia (rigidity, bradykinesia), dysarthria, abnormalities of eye movements and gait, and hyperreflexia in the later stages of the disease. There is a strong correlation between the duration of the disease and the progression of motor and cognitive signs and symptoms., The diagnosis of HDL2 is established in a proband with characteristic clinical findings and heterozygous expansion of 40 or more CTG trinucleotide repeats in JPH3 identified by molecular genetic testing., Treatment of manifestations: Treatment is symptomatic and is presumably similar to that for HD and other neurodegenerative disorders \u2013 although this must be considered speculative pending objective data. Pharmacologic agents that may suppress abnormal movements include tetrabenazine and its derivatives or low-dose neuroleptic agents such as fluphenazine and haloperidol. Remove loose rugs and clutter from the individual's home and minimize or eliminate the need for stairs to help prevent falls and other injuries; physical therapy evaluation and treatment for mobility issues; speech therapy, communication devices, and environmental modifications for dysarthria; speech-language pathology and nutrition referrals for dysphagia; food should be prepared in such a manner as to prevent choking; feeding changes when needed to minimize risk of aspiration; driving may need to be curtailed or limited to prevent risk of accidents; planning for financial matters; environmental interventions for cognitive issues; antidepressants, antipsychotics, mood stabilizers (lithium, valproic acid, carbamazepine, and lamotrigine), electroconvulsive therapy, and occasionally stimulants may improve psychiatric manifestations. Education about the course of disease; social work and care coordination support. Surveillance: Annual evaluation or more frequently as needed to assess motor skills including gait and abnormal movements; physical therapy assessment of mobility and appropriate strategies or devices to minimize falls; assess cognitive skills and driving safety to assure that affected individuals do not present a danger to themselves or others; assess weight, nutrition, swallowing, and risk of aspiration in order to implement feeding changes when necessary; assess for psychiatric manifestations, including mood, suicidality, anxiety, irritability, and apathy; assess sleep and sexual concerns; assess family needs; assess planning for future (financial, legal issues). Agents/circumstances to avoid: Any agents that increase ataxia should be used with caution; begin psychoactive medicines at lower doses and increase doses carefully; minimize polypharmacy, which may increase the risk of delirium., HDL2 is inherited in an autosomal dominant manner. Most individuals with HDL2 have an affected parent. At conception, each child of an individual with HDL2 has a 50% chance of inheriting the HDL2-causing allele. Offspring who inherit a pathogenic (full-penetrance) HDL2-causing allele (\u226540 CTG repeats) are considered at risk of developing HDL2 in their lifetime; offspring who inherit an allele of questionable significance (29-39 CTG repeats) may or may not develop manifestations of HDL2. Testing of asymptomatic adults at risk for HDL2 is possible once a heterozygous expansion of a CTG repeat in JPH3 has been identified in an affected family member. Testing for the JPH3 CTG repeat expansion in the absence of definite manifestations of the disease is predictive testing. Prudence suggests following the same genetic testing guidelines used for HD, including counseling prior to testing, a confidant to serve as a social support, and availability of counseling following the disclosure of genetic results. If the presence of an HDL2-causing allele has been confirmed in the affected parent or in an affected relative of the at-risk parent, prenatal and preimplantation genetic testing are possible.",
+ "language": "eng",
+ "note": "PMID: 20301701\nThis CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: url:https://www.ncbi.nlm.nih.gov/books/NBK1529"
+},
+{
+ "id": "genereviews:NBK153723",
+ "manubot_success": true,
+ "link": "http://www.ncbi.nlm.nih.gov/books/NBK153723/",
+ "title": "Autosomal Dominant Tubulointerstitial Kidney Disease \u2013 MUC1",
+ "type": "chapter",
+ "doi": "",
+ "authors": [
+ ["Anthony J.", "Bleyer"],
+ ["Martina", "\u017divn\u00e1"],
+ ["Kendrah", "Kidd"],
+ ["Stanislav", "Kmoch"]
+ ],
+ "publisher": "GeneReviews\u00ae",
+ "issn": "",
+ "date": "1993-01-01",
+ "abstract": "Autosomal dominant tubulointerstitial kidney disease \u2013 MUC1 (ADTKD-MUC1) is characterized by slowly progressive tubulointerstitial disease that leads to end-stage renal disease (ESRD) and the need for dialysis or kidney transplantation. The rate of loss of kidney function for individuals is variable within and between families, with a median age of onset of end-stage renal disease (ESRD) of 46 years (range: ages 20-70 years). There are no other systemic manifestations., The diagnosis of ADTKD-MUC1 is established in a proband with suggestive clinical findings and molecular genetic testing that reveals a heterozygous pathogenic variant in MUC1 that results in the creation of a specific frameshift protein (MUC1fs) responsible for the pathogenic changes in this disorder., Treatment of manifestations: Treatment follows standard guidelines for chronic kidney disease \u2013 based on the level of the serum creatinine and the estimated glomerular filtration rate (eGFR) \u2013 and its sequelae, which can include hypertension, anemia, and gout. Affected individuals are encouraged to prepare for kidney transplantation, the definitive treatment of ADTKD-MUC1, by staying in optimal health (e.g., by exercising, avoiding obesity and tobacco usage, and maintaining strict control of hypertension, dyslipidemia, and other cardiovascular risk factors). Kidney transplantation is curative; the outcome is excellent. Surveillance: Measurement of hemoglobin, serum concentrations of uric acid and creatinine and blood pressure annually prior to entering CKD Stage 3. Thereafter, follow up is determined by the treating nephrologist. Agents/circumstances to avoid: Affected individuals should follow general recommendations for chronic kidney disease. Pregnancy management: The use of ACE inhibitors should be avoided during pregnancy, as they can result in fetal damage and death. Women who are pregnant, planning a pregnancy, or not actively avoiding pregnancy should be transitioned to another antihypertensive medication. Allopurinol therapy should be stopped during pregnancy, if possible. Evaluation of relatives at risk: For early diagnosis and treatment: It is appropriate to identify as early as possible apparently asymptomatic at-risk adult relatives who have the familial MUC1 variant in order to monitor their serum creatinine levels and promptly initiate treatment and awareness of agents/circumstances to avoid. For kidney donation: Any relative who is a potential kidney donor should undergo molecular genetic testing to clarify the relative's genetic status so that only those who do not have the familial MUC1 pathogenic variant are evaluated further., ADTKD-MUC1 is inherited in an autosomal dominant manner. Each child of an affected individual has a 50% chance of inheriting the MUC1 pathogenic variant. Prenatal testing for MUC1 pathogenic variants is not available in the US at this time.",
+ "language": "eng",
+ "note": "PMID: 23946964\nThis CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: url:https://www.ncbi.nlm.nih.gov/books/NBK153723"
+},
+{
+ "id": "genereviews:NBK1438",
+ "manubot_success": true,
+ "link": "http://www.ncbi.nlm.nih.gov/books/NBK1438/",
+ "title": "Spinocerebellar Ataxia Type 17",
+ "type": "chapter",
+ "doi": "",
+ "authors": [
+ ["Yasuko", "Toyoshima"],
+ ["Osamu", "Onodera"],
+ ["Mitsunori", "Yamada"],
+ ["Shoji", "Tsuji"],
+ ["Hitoshi", "Takahashi"]
+ ],
+ "publisher": "GeneReviews\u00ae",
+ "issn": "",
+ "date": "1993-01-01",
+ "abstract": "Spinocerebellar ataxia type 17 (SCA17) is characterized by ataxia, dementia, and involuntary movements, including chorea and dystonia. Psychiatric symptoms, pyramidal signs, and rigidity are common. The age of onset ranges from three to 55 years. Individuals with full-penetrance alleles develop neurologic and/or psychiatric symptoms by age 50 years. Ataxia and psychiatric abnormalities are frequently the initial findings, followed by involuntary movement, parkinsonism, dementia, and pyramidal signs. Brain MRI shows variable atrophy of the cerebrum, brain stem, and cerebellum. The clinical features correlate with the length of the polyglutamine expansion but are not absolutely predictive of the clinical course., The diagnosis of SCA17 is established in a proband by identification of an abnormal CAG/CAA repeat expansion in TBP. Affected individuals usually have more than 41 repeats. The CAA and CAG codons both encode glutamine residues resulting in a pathogenic polyglutamine expansion., Treatment of manifestations: Psychotropic medications for psychiatric issues, anti-seizure medication for seizures (ASM); botulinum toxin injections for dystonia; adaptation of the environment to accommodate dementia. Prevention of secondary complications: Side effects of psychotropic medications and ASMs may require total or intermittent discontinuation of the treatment or reduction in dose. Surveillance: Annual or semiannual evaluation by a neurologist or more frequently if symptoms are progressing rapidly. Agents/circumstances to avoid: Sedative/hypnotic agents, such as ethanol or certain medications, may exacerbate incoordination., SCA17 is inherited in an autosomal dominant manner. Offspring of affected individuals are at a 50% risk of inheriting the expanded TBP allele. The age of onset, severity, specific symptoms, and progression of the disease are variable and cannot be precisely predicted by family history or size of expansion. Prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible if the diagnosis has been established in an affected family member by molecular genetic testing.",
+ "language": "eng",
+ "note": "PMID: 20301611\nThis CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: url:https://www.ncbi.nlm.nih.gov/books/NBK1438"
+},
+{
+ "id": "pmid:12764052",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/12764052",
+ "title": "A novel autosomal dominant spinocerebellar ataxia (SCA22) linked to chromosome 1p21-q23.",
+ "type": "article-journal",
+ "doi": "10.1093/brain/awg130",
+ "authors": [
+ ["Ming-Yi", "Chung"],
+ ["Yi-Chun", "Lu"],
+ ["Nai-Chia", "Cheng"],
+ ["Bing-Wen", "Soong"]
+ ],
+ "publisher": "Brain : a journal of neurology",
+ "issn": "0006-8950",
+ "date": "2003-06-01",
+ "abstract": "The autosomal dominant cerebellar ataxias (ADCA) are a clinically, pathologically and genetically heterogeneous group of disorders. Ten responsible genes have been identified for spinocerebellar ataxia types SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA10, SCA12 and SCA17, and dentatorubral pallidoluysian atrophy (DRPLA). The mutation is caused by an expansion of a CAG, CTG or ATTCT repeat sequence of these genes. Six additional loci, SCA4, SCA5, SCA11, SCA13, SCA14 and SCA16 have also been mapped. The growing heterogeneity of the autosomal dominant forms of these diseases shows that the genetic aetiologies of at least 20% of ADCA have yet to be elucidated. We ascertained and clinically characterized a four-generation Chinese pedigree segregating an autosomal dominant phenotype for cerebellar ataxia. Direct mutation analysis, linkage analysis for all known SCA loci and a genome-wide linkage study were performed. Direct mutation analysis excluded SCA1, 2, 3, 6, 7, 8, 10, 12, 17 and DRPLA, and genetic linkage analysis excluded SCA4, 5, 11, 13, 14 and 16. The genome-wide linkage study suggested linkage to a locus on chromosome 1p21-q23, with the highest two-point LOD score at D1S1167 (Zmax = 3.46 at theta = 0.00). Multipoint analysis and haplotype reconstruction traced this novel SCA locus (SCA22) to a 43.7-cM interval flanked by D1S206 and D1S2878 (Zmax = 3.78 under four liability classes, and 2.67 using affected-only method). The age at onset ranged from 10 to 46 years. All affected members had gait ataxia with variable features of dysarthria and hyporeflexia. Head MRI showed homogeneous atrophy of the cerebellum without involvement of the brainstem. In six parent-child pairs, median onset occurred 10 years earlier in offspring than in their parents, suggesting anticipation. This family is distinct from other families with SCA and is characterized by a slowly progressive, pure cerebellar ataxia.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12764052"
+},
+{
+ "id": "pmid:28444220",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/28444220",
+ "title": "A panel study on patients with dominant cerebellar ataxia highlights the frequency of channelopathies.",
+ "type": "article-journal",
+ "doi": "10.1093/brain/awx081",
+ "authors": [
+ ["Marie", "Coutelier"],
+ ["Giulia", "Coarelli"],
+ ["Marie-Lorraine", "Monin"],
+ ["Juliette", "Konop"],
+ ["Claire-Sophie", "Davoine"],
+ ["Christelle", "Tesson"],
+ ["R\u00e9mi", "Valter"],
+ ["Mathieu", "Anheim"],
+ ["Anthony", "Behin"],
+ ["Giovanni", "Castelnovo"],
+ ["Perrine", "Charles"],
+ ["Albert", "David"],
+ ["Claire", "Ewenczyk"],
+ ["M\u00e9lanie", "Fradin"],
+ ["Cyril", "Goizet"],
+ ["Didier", "Hannequin"],
+ ["Pierre", "Labauge"],
+ ["Florence", "Riant"],
+ ["Pierre", "Sarda"],
+ ["Yves", "Sznajer"],
+ ["Fran\u00e7ois", "Tison"],
+ ["Urielle", "Ullmann"],
+ ["Lionel", "Van Maldergem"],
+ ["Fanny", "Mochel"],
+ ["Alexis", "Brice"],
+ ["Giovanni", "Stevanin"],
+ ["Alexandra", "Durr"]
+ ],
+ "publisher": "Brain : a journal of neurology",
+ "issn": "1460-2156",
+ "date": "2017-06-01",
+ "abstract": "Autosomal dominant cerebellar ataxias have a marked heterogeneous genetic background, with mutations in 34 genes identified so far. This large amount of implicated genes accounts for heterogeneous clinical presentations, making genotype-phenotype correlations a major challenge in the field. While polyglutamine ataxias, linked to CAG repeat expansions in genes such as ATXN1, ATXN2, ATXN3, ATXN7, CACNA1A and TBP, have been extensively characterized in large cohorts, there is a need for comprehensive assessment of frequency and phenotype of more 'conventional' ataxias. After exclusion of CAG/polyglutamine expansions in spinocerebellar ataxia genes in 412 index cases with dominantly inherited cerebellar ataxias, we aimed to establish the relative frequencies of mutations in other genes, with an approach combining panel sequencing and TaqMan\u00ae polymerase chain reaction assay. We found relevant genetic variants in 59 patients (14.3%). The most frequently mutated were channel genes [CACNA1A (n = 16), KCND3 (n = 4), KCNC3 (n = 2) and KCNA1 (n = 2)]. Deletions in ITPR1 (n = 11) were followed by biallelic variants in SPG7 (n = 9). Variants in AFG3L2 (n = 7) came next in frequency, and variants were rarely found in STBN2 (n = 2), ELOVL5, FGF14, STUB1 and TTBK2 (n = 1 each). Interestingly, possible risk factor variants were detected in SPG7 and POLG. Clinical comparisons showed that ataxias due to channelopathies had a significantly earlier age at onset with an average of 24.6 years, versus 40.9 years for polyglutamine expansion spinocerebellar ataxias and 37.8 years for SPG7-related forms (P = 0.001). In contrast, disease duration was significantly longer in the former (20.5 years versus 9.3 and 13.7, P=0.001), though for similar functional stages, indicating slower progression of the disease. Of interest, intellectual deficiency was more frequent in channel spinocerebellar ataxias, while cognitive impairment in adulthood was similar among the three groups. Similar differences were found among a single gene group, comparing 23 patients with CACNA1A expansions (spinocerebellar ataxia 6) to 22 patients with CACNA1A point mutations, which had lower average age at onset (25.2 versus 47.3 years) with longer disease duration (18.7 versus 10.9), but lower severity indexes (0.39 versus 0.44), indicating slower progression of the disease. In conclusion, we identified relevant genetic variations in up to 15% of cases after exclusion of polyglutamine expansion spinocerebellar ataxias, and confirmed CACNA1A and SPG7 as major ataxia genes. We could delineate firm genotype-phenotype correlations that are important for genetic counselling and of possible prognostic value.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28444220"
+},
+{
+ "id": "pmid:30109267",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30109267",
+ "title": "Noncoding repeat expansions for ALS in Japan are associated with the",
+ "type": "article-journal",
+ "doi": "10.1212/nxg.0000000000000252",
+ "authors": [
+ ["Makito", "Hirano"],
+ ["Makoto", "Samukawa"],
+ ["Chiharu", "Isono"],
+ ["Kazumasa", "Saigoh"],
+ ["Yusaku", "Nakamura"],
+ ["Susumu", "Kusunoki"]
+ ],
+ "publisher": "Neurology. Genetics",
+ "issn": "2376-7839",
+ "date": "2018-08-01",
+ "abstract": "To assess the contribution of noncoding repeat expansions in Japanese patients with amyotrophic lateral sclerosis (ALS).",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30109267"
+},
+{
+ "id": "pmid:39913612",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/39913612",
+ "title": "ALS plasma biomarkers reveal neurofilament and pTau correlate with disease onset and progression.",
+ "type": "article-journal",
+ "doi": "10.1002/acn3.70001",
+ "authors": [
+ ["Eleanor V", "Thomas"],
+ ["Changee", "Han"],
+ ["Woo Jae", "Kim"],
+ ["Seneshaw", "Asress"],
+ ["Yingjie", "Li"],
+ ["Jennifer A", "Taylor"],
+ ["Marla", "Gearing"],
+ ["Christina N", "Fournier"],
+ ["Zachary T", "McEachin"],
+ ["Nicholas T", "Seyfried"],
+ ["Jonathan D", "Glass"]
+ ],
+ "publisher": "Annals of clinical and translational neurology",
+ "issn": "2328-9503",
+ "date": "2025-02-06",
+ "abstract": "We performed a pilot screen to assess the utility of the NULISA\u2122 (Nucleic-acid-Linked Immuno-Sandwich Assay) platform in the identification of amyotrophic lateral sclerosis (ALS) biomarkers.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39913612"
+},
+{
+ "id": "pmid:34687211",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/34687211",
+ "title": "SLITRK2, an X-linked modifier of the age at onset in C9orf72 frontotemporal lobar degeneration.",
+ "type": "article-journal",
+ "doi": "10.1093/brain/awab171",
+ "authors": [
+ ["Mathieu", "Barbier"],
+ ["Agn\u00e8s", "Camuzat"],
+ ["Khalid El", "Hachimi"],
+ ["Justine", "Guegan"],
+ ["Daisy", "Rinaldi"],
+ ["Serena", "Lattante"],
+ ["Marion", "Houot"],
+ ["Raquel", "S\u00e1nchez-Valle"],
+ ["Mario", "Sabatelli"],
+ ["Anna", "Antonell"],
+ ["Laura", "Molina-Porcel"],
+ ["Fabienne", "Clot"],
+ ["Philippe", "Couratier"],
+ ["Emma", "van der Ende"],
+ ["Julie", "van der Zee"],
+ ["Claudia", "Manzoni"],
+ ["William", "Camu"],
+ ["C\u00e9cile", "Cazeneuve"],
+ ["Fran\u00e7ois", "Sellal"],
+ ["Mira", "Didic"],
+ ["V\u00e9ronique", "Golfier"],
+ ["Florence", "Pasquier"],
+ ["Charles", "Duyckaerts"],
+ ["Giacomina", "Rossi"],
+ ["Amalia C", "Bruni"],
+ ["Victoria", "Alvarez"],
+ ["Estrella", "G\u00f3mez-Tortosa"],
+ ["Alexandre", "de Mendon\u00e7a"],
+ ["Caroline", "Graff"],
+ ["Mario", "Masellis"],
+ ["Benedetta", "Nacmias"],
+ ["Badreddine Mohand", "Oumoussa"],
+ ["Ludmila", "Jornea"],
+ ["Sylvie", "Forlani"],
+ ["Viviana", "Van Deerlin"],
+ ["Jonathan D", "Rohrer"],
+ ["Ellen", "Gelpi"],
+ ["Rosa", "Rademakers"],
+ ["John", "Van Swieten"],
+ ["Eric", "Le Guern"],
+ ["Christine", "Van Broeckhoven"],
+ ["Raffaele", "Ferrari"],
+ ["Emmanuelle", "G\u00e9nin"],
+ ["Alexis", "Brice"],
+ ["Isabelle", "Le Ber"]
+ ],
+ "publisher": "Brain : a journal of neurology",
+ "issn": "1460-2156",
+ "date": "2021-10-22",
+ "abstract": "The G4C2-repeat expansion in C9orf72 is the most common cause of frontotemporal dementia and of amyotrophic lateral sclerosis. The variability of age at onset and phenotypic presentations is a hallmark of C9orf72 disease. In this study, we aimed to identify modifying factors of disease onset in C9orf72 carriers using a family-based approach, in pairs of C9orf72 carrier relatives with concordant or discordant age at onset. Linkage and association analyses provided converging evidence for a locus on chromosome Xq27.3. The minor allele A of rs1009776 was associated with an earlier onset (P\u2009=\u20091 \u00d7 10-5). The association with onset of dementia was replicated in an independent cohort of unrelated C9orf72 patients (P\u2009=\u20090.009). The protective major allele delayed the onset of dementia from 5 to 13\u2009years on average depending on the cohort considered. The same trend was observed in an independent cohort of C9orf72 patients with extreme deviation of the age at onset (P\u2009=\u20090.055). No association of rs1009776 was detected in GRN patients, suggesting that the effect of rs1009776 was restricted to the onset of dementia due to C9orf72. The minor allele A is associated with a higher SLITRK2 expression based on both expression quantitative trait loci (eQTL) databases and in-house expression studies performed on C9orf72 brain tissues. SLITRK2 encodes for a post-synaptic adhesion protein. We further show that synaptic vesicle glycoprotein 2 and synaptophysin, two synaptic vesicle proteins, were decreased in frontal cortex of C9orf72 patients carrying the minor allele. Upregulation of SLITRK2 might be associated with synaptic dysfunctions and drives adverse effects in C9orf72 patients that could be modulated in those carrying the protective allele. How the modulation of SLITRK2 expression affects synaptic functions and influences the disease onset of dementia in C9orf72 carriers will require further investigations. In summary, this study describes an original approach to detect modifier genes in rare diseases and reinforces rising links between C9orf72 and synaptic dysfunctions that might directly influence the occurrence of first symptoms.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34687211"
+},
+{
+ "id": "pmid:30347338",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30347338",
+ "title": "Response to the commentary \"The effect of C9orf72 intermediate repeat expansions in neurodegenerative and autoimmune diseases\" by Biasiotto G and Zanella I.",
+ "type": "article-journal",
+ "doi": "10.1016/j.msard.2018.10.007",
+ "authors": [
+ ["Cinzia", "Tiloca"],
+ ["Melissa", "Sorosina"],
+ ["Federica", "Esposito"],
+ ["Silvia", "Peroni"],
+ ["Claudia", "Colombrita"],
+ ["Nicola", "Ticozzi"],
+ ["Antonia", "Ratti"],
+ ["Filippo", "Martinelli-Boneschi"],
+ ["Vincenzo", "Silani"]
+ ],
+ "publisher": "Multiple sclerosis and related disorders",
+ "issn": "2211-0356",
+ "date": "2018-10-14",
+ "abstract": "",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30347338"
+},
+{
+ "id": "pmid:30252044",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30252044",
+ "title": "A C6orf10/LOC101929163 locus is associated with age of onset in C9orf72 carriers.",
+ "type": "article-journal",
+ "doi": "10.1093/brain/awy238",
+ "authors": [
+ ["Ming", "Zhang"],
+ ["Raffaele", "Ferrari"],
+ ["Maria Carmela", "Tartaglia"],
+ ["Julia", "Keith"],
+ ["Ezequiel I", "Surace"],
+ ["Uri", "Wolf"],
+ ["Christine", "Sato"],
+ ["Mark", "Grinberg"],
+ ["Yan", "Liang"],
+ ["Zhengrui", "Xi"],
+ ["Kyle", "Dupont"],
+ ["Philip", "McGoldrick"],
+ ["Anna", "Weichert"],
+ ["Paul M", "McKeever"],
+ ["Raphael", "Schneider"],
+ ["Michael D", "McCorkindale"],
+ ["Claudia", "Manzoni"],
+ ["Rosa", "Rademakers"],
+ ["Neill R", "Graff-Radford"],
+ ["Dennis W", "Dickson"],
+ ["Joseph E", "Parisi"],
+ ["Bradley F", "Boeve"],
+ ["Ronald C", "Petersen"],
+ ["Bruce L", "Miller"],
+ ["William W", "Seeley"],
+ ["John C", "van Swieten"],
+ ["Jeroen", "van Rooij"],
+ ["Yolande", "Pijnenburg"],
+ ["Julie", "van der Zee"],
+ ["Christine", "Van Broeckhoven"],
+ ["Isabelle", "Le Ber"],
+ ["Vivianna", "Van Deerlin"],
+ ["EunRan", "Suh"],
+ ["Jonathan D", "Rohrer"],
+ ["Simon", "Mead"],
+ ["Caroline", "Graff"],
+ ["Linn", "\u00d6ijerstedt"],
+ ["Stuart", "Pickering-Brown"],
+ ["Sara", "Rollinson"],
+ ["Giacomina", "Rossi"],
+ ["Fabrizio", "Tagliavini"],
+ ["William S", "Brooks"],
+ ["Carol", "Dobson-Stone"],
+ ["Glenda M", "Halliday"],
+ ["John R", "Hodges"],
+ ["Olivier", "Piguet"],
+ ["Giuliano", "Binetti"],
+ ["Luisa", "Benussi"],
+ ["Roberta", "Ghidoni"],
+ ["Benedetta", "Nacmias"],
+ ["Sandro", "Sorbi"],
+ ["Amalia C", "Bruni"],
+ ["Daniela", "Galimberti"],
+ ["Elio", "Scarpini"],
+ ["Innocenzo", "Rainero"],
+ ["Elisa", "Rubino"],
+ ["Jordi", "Clarimon"],
+ ["Alberto", "Lle\u00f3"],
+ ["Agustin", "Ruiz"],
+ ["Isabel", "Hern\u00e1ndez"],
+ ["Pau", "Pastor"],
+ ["Monica", "Diez-Fairen"],
+ ["Barbara", "Borroni"],
+ ["Florence", "Pasquier"],
+ ["Vincent", "Deramecourt"],
+ ["Thibaud", "Lebouvier"],
+ ["Robert", "Perneczky"],
+ ["Janine", "Diehl-Schmid"],
+ ["Jordan", "Grafman"],
+ ["Edward D", "Huey"],
+ ["Richard", "Mayeux"],
+ ["Michael A", "Nalls"],
+ ["Dena", "Hernandez"],
+ ["Andrew", "Singleton"],
+ ["Parastoo", "Momeni"],
+ ["Zhen", "Zeng"],
+ ["John", "Hardy"],
+ ["Janice", "Robertson"],
+ ["Lorne", "Zinman"],
+ ["Ekaterina", "Rogaeva"]
+ ],
+ "publisher": "Brain : a journal of neurology",
+ "issn": "1460-2156",
+ "date": "2018-10-01",
+ "abstract": "The G4C2-repeat expansion in C9orf72 is the most common known cause of amyotrophic lateral sclerosis and frontotemporal dementia. The high phenotypic heterogeneity of C9orf72 patients includes a wide range in age of onset, modifiers of which are largely unknown. Age of onset could be influenced by environmental and genetic factors both of which may trigger DNA methylation changes at CpG sites. We tested the hypothesis that age of onset in C9orf72 patients is associated with some common single nucleotide polymorphisms causing a gain or loss of CpG sites and thus resulting in DNA methylation alterations. Combined analyses of epigenetic and genetic data have the advantage of detecting functional variants with reduced likelihood of false negative results due to excessive correction for multiple testing in genome-wide association studies. First, we estimated the association between age of onset in C9orf72 patients (n = 46) and the DNA methylation levels at all 7603 CpG sites available on the 450 k BeadChip that are mapped to common single nucleotide polymorphisms. This was followed by a genetic association study of the discovery (n = 144) and replication (n = 187) C9orf72 cohorts. We found that age of onset was reproducibly associated with polymorphisms within a 124.7 kb linkage disequilibrium block tagged by top-significant variation, rs9357140, and containing two overlapping genes (LOC101929163 and C6orf10). A meta-analysis of all 331 C9orf72 carriers revealed that every A-allele of rs9357140 reduced hazard by 30% (P = 0.0002); and the median age of onset in AA-carriers was 6 years later than GG-carriers. In addition, we investigated a cohort of C9orf72 negative patients (n = 2634) affected by frontotemporal dementia and/or amyotrophic lateral sclerosis; and also found that the AA-genotype of rs9357140 was associated with a later age of onset (adjusted P = 0.007 for recessive model). Phenotype analyses detected significant association only in the largest subgroup of patients with frontotemporal dementia (n = 2142, adjusted P = 0.01 for recessive model). Gene expression studies of frontal cortex tissues from 25 autopsy cases affected by amyotrophic lateral sclerosis revealed that the G-allele of rs9357140 is associated with increased brain expression of LOC101929163 (a non-coding RNA) and HLA-DRB1 (involved in initiating immune responses), while the A-allele is associated with their reduced expression. Our findings suggest that carriers of the rs9357140 GG-genotype (linked to an earlier age of onset) might be more prone to be in a pro-inflammatory state (e.g. by microglia) than AA-carriers. Further, investigating the functional links within the C6orf10/LOC101929163/HLA-DRB1 pathway will be critical to better define age-dependent pathogenesis of frontotemporal dementia and amyotrophic lateral sclerosis.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30252044"
+},
+{
+ "id": "pmid:30150298",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30150298",
+ "title": "The",
+ "type": "article-journal",
+ "doi": "10.1128/mcb.00155-18",
+ "authors": [
+ ["Vitalay", "Fomin"],
+ ["Patricia", "Richard"],
+ ["Mainul", "Hoque"],
+ ["Cynthia", "Li"],
+ ["Zhuoying", "Gu"],
+ ["Mercedes", "Fissore-O'Leary"],
+ ["Bin", "Tian"],
+ ["Carol", "Prives"],
+ ["James L", "Manley"]
+ ],
+ "publisher": "Molecular and cellular biology",
+ "issn": "1098-5549",
+ "date": "2018-10-29",
+ "abstract": "A GGGGCC repeat expansion in the",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30150298"
+},
+{
+ "id": "pmid:29973287",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/29973287",
+ "title": "Dipeptide repeat proteins activate a heat shock response found in C9ORF72-ALS/FTLD patients.",
+ "type": "article-journal",
+ "doi": "10.1186/s40478-018-0555-8",
+ "authors": [
+ ["Daniel A", "Mordes"],
+ ["Mercedes", "Prudencio"],
+ ["Lindsey D", "Goodman"],
+ ["Joseph R", "Klim"],
+ ["Rob", "Moccia"],
+ ["Francesco", "Limone"],
+ ["Olli", "Pietilainen"],
+ ["Kaitavjeet", "Chowdhary"],
+ ["Dennis W", "Dickson"],
+ ["Rosa", "Rademakers"],
+ ["Nancy M", "Bonini"],
+ ["Leonard", "Petrucelli"],
+ ["Kevin", "Eggan"]
+ ],
+ "publisher": "Acta neuropathologica communications",
+ "issn": "2051-5960",
+ "date": "2018-07-04",
+ "abstract": "A hexanucleotide (GGGGCC) repeat expansion in C9ORF72 is the most common genetic contributor to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Reduced expression of the C9ORF72 gene product has been proposed as a potential contributor to disease pathogenesis. Additionally, repetitive RNAs and dipeptide repeat proteins (DPRs), such as poly-GR, can be produced by this hexanucleotide expansion that disrupt a number of cellular processes, potentially contributing to neural degeneration. To better discern which of these mechanisms leads to disease-associated changes in patient brains, we analyzed gene expression data generated from the cortex and cerebellum. We found that transcripts encoding heat shock proteins (HSPs) regulated by the HSF1 transcription factor were significantly induced in C9ORF72-ALS/FTLD patients relative to both sporadic ALS/FTLD cases and controls. Treatment of human neurons with chemically synthesized DPRs was sufficient to activate a similar transcriptional response. Expression of GGGGCC repeats and also poly-GR in the brains of Drosophila lead to the upregulation of HSF1 and the same highly-conserved HSPs. Additionally, HSF1 was a modifier of poly-GR toxicity in Drosophila. Our results suggest that the expression of DPRs are associated with upregulation of HSF1 and activation of a heat shock response in C9ORF72-ALS/FTLD.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29973287"
+},
+{
+ "id": "pmid:28192553",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/28192553",
+ "title": "Clinical Evidence of Disease Anticipation in Families Segregating a C9orf72 Repeat Expansion.",
+ "type": "article-journal",
+ "doi": "10.1001/jamaneurol.2016.4847",
+ "authors": [
+ ["Sara", "Van Mossevelde"],
+ ["Julie", "van der Zee"],
+ ["Ilse", "Gijselinck"],
+ ["Kristel", "Sleegers"],
+ ["Jan", "De Bleecker"],
+ ["Anne", "Sieben"],
+ ["Rik", "Vandenberghe"],
+ ["Tim", "Van Langenhove"],
+ ["Jonathan", "Baets"],
+ ["Olivier", "Deryck"],
+ ["Patrick", "Santens"],
+ ["Adrian", "Ivanoiu"],
+ ["Christiana", "Willems"],
+ ["Veerle", "B\u00e4umer"],
+ ["Marleen", "Van den Broeck"],
+ ["Karin", "Peeters"],
+ ["Maria", "Mattheijssens"],
+ ["Peter", "De Jonghe"],
+ ["Patrick", "Cras"],
+ ["Jean-Jacques", "Martin"],
+ ["Marc", "Cruts"],
+ ["Peter P", "De Deyn"],
+ ["Sebastiaan", "Engelborghs"],
+ ["Christine", "Van Broeckhoven"]
+ ],
+ "publisher": "JAMA neurology",
+ "issn": "2168-6157",
+ "date": "2017-04-01",
+ "abstract": "Patients carrying a C9orf72 repeat expansion leading to frontotemporal dementia and/or amyotrophic lateral sclerosis have highly variable ages at onset of disease, suggesting the presence of modifying factors.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28192553"
+},
+{
+ "id": "pmid:27097283",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27097283",
+ "title": "C9orf72 Hexanucleotide Expansions Are Associated with Altered Endoplasmic Reticulum Calcium Homeostasis and Stress Granule Formation in Induced Pluripotent Stem Cell-Derived Neurons from Patients with Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.",
+ "type": "article-journal",
+ "doi": "10.1002/stem.2388",
+ "authors": [
+ ["Ruxandra", "Dafinca"],
+ ["Jakub", "Scaber"],
+ ["Nida'a", "Ababneh"],
+ ["Tatjana", "Lalic"],
+ ["Gregory", "Weir"],
+ ["Helen", "Christian"],
+ ["Jane", "Vowles"],
+ ["Andrew G L", "Douglas"],
+ ["Alexandra", "Fletcher-Jones"],
+ ["Cathy", "Browne"],
+ ["Mahito", "Nakanishi"],
+ ["Martin R", "Turner"],
+ ["Richard", "Wade-Martins"],
+ ["Sally A", "Cowley"],
+ ["Kevin", "Talbot"]
+ ],
+ "publisher": "Stem cells (Dayton, Ohio)",
+ "issn": "1549-4918",
+ "date": "2016-05-04",
+ "abstract": "An expanded hexanucleotide repeat in a noncoding region of the C9orf72 gene is a major cause of amyotrophic lateral sclerosis (ALS), accounting for up to 40% of familial cases and 7% of sporadic ALS in European populations. We have generated induced pluripotent stem cells (iPSCs) from fibroblasts of patients carrying C9orf72 hexanucleotide expansions, differentiated these to functional motor and cortical neurons, and performed an extensive phenotypic characterization. In C9orf72 iPSC-derived motor neurons, decreased cell survival is correlated with dysfunction in Ca(2+) homeostasis, reduced levels of the antiapoptotic protein Bcl-2, increased endoplasmic reticulum (ER) stress, and reduced mitochondrial membrane potential. Furthermore, C9orf72 motor neurons, and also cortical neurons, show evidence of abnormal protein aggregation and stress granule formation. This study is an extensive characterization of iPSC-derived motor neurons as cellular models of ALS carrying C9orf72 hexanucleotide repeats, which describes a novel pathogenic link between C9orf72 mutations, dysregulation of calcium signaling, and altered proteostasis and provides a potential pharmacological target for the treatment of ALS and the related neurodegenerative disease frontotemporal dementia. Stem Cells 2016;34:2063-2078.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27097283"
+},
+{
+ "id": "pmid:22766072",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22766072",
+ "title": "C9ORF72 repeat expansion in a large Italian ALS cohort: evidence of a founder effect.",
+ "type": "article-journal",
+ "doi": "10.1016/j.neurobiolaging.2012.06.008",
+ "authors": [
+ ["Antonia", "Ratti"],
+ ["Lucia", "Corrado"],
+ ["Barbara", "Castellotti"],
+ ["Roberto", "Del Bo"],
+ ["Isabella", "Fogh"],
+ ["Cristina", "Cereda"],
+ ["Cinzia", "Tiloca"],
+ ["Carla", "D'Ascenzo"],
+ ["Alessandra", "Bagarotti"],
+ ["Viviana", "Pensato"],
+ ["Michela", "Ranieri"],
+ ["Stella", "Gagliardi"],
+ ["Daniela", "Calini"],
+ ["Letizia", "Mazzini"],
+ ["Franco", "Taroni"],
+ ["Stefania", "Corti"],
+ ["Mauro", "Ceroni"],
+ ["Gaia D", "Oggioni"],
+ ["Kuang", "Lin"],
+ ["John F", "Powell"],
+ ["Gianni", "Sorar\u00f9"],
+ ["Nicola", "Ticozzi"],
+ ["Giacomo P", "Comi"],
+ ["Sandra", "D'Alfonso"],
+ ["Cinzia", "Gellera"],
+ ["Vincenzo", "Silani"]
+ ],
+ "publisher": "Neurobiology of aging",
+ "issn": "1558-1497",
+ "date": "2012-07-04",
+ "abstract": "A hexanucleotide repeat expansion (RE) in C9ORF72 gene was recently reported as the main cause of amyotrophic lateral sclerosis (ALS) and cases with frontotemporal dementia. We screened C9ORF72 in a large cohort of 259 familial ALS, 1275 sporadic ALS, and 862 control individuals of Italian descent. We found RE in 23.9% familial ALS, 5.1% sporadic ALS, and 0.2% controls. Two cases carried the RE together with mutations in other ALS-associated genes. The phenotype of RE carriers was characterized by bulbar-onset, shorter survival, and association with cognitive and behavioral impairment. Extrapyramidal and cerebellar signs were also observed in few patients. Genotype data revealed that 95% of RE carriers shared a restricted 10-single nucleotide polymorphism haplotype within the previously reported 20-single nucleotide polymorphism risk haplotype, detectable in only 27% of nonexpanded ALS cases and in 28% of controls, suggesting a common founder with cohorts of North European ancestry. Although C9ORF72 RE segregates with disease, the identification of RE both in controls and in patients carrying additional pathogenic mutations suggests that penetrance and phenotypic expression of C9ORF72 RE may depend on additional genetic risk factors.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22766072"
+},
+{
+ "id": "pmid:21944779",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21944779",
+ "title": "A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD.",
+ "type": "article-journal",
+ "doi": "10.1016/j.neuron.2011.09.010",
+ "authors": [
+ ["Alan E", "Renton"],
+ ["Elisa", "Majounie"],
+ ["Adrian", "Waite"],
+ ["Javier", "Sim\u00f3n-S\u00e1nchez"],
+ ["Sara", "Rollinson"],
+ ["J Raphael", "Gibbs"],
+ ["Jennifer C", "Schymick"],
+ ["Hannu", "Laaksovirta"],
+ ["John C", "van Swieten"],
+ ["Liisa", "Myllykangas"],
+ ["Hannu", "Kalimo"],
+ ["Anders", "Paetau"],
+ ["Yevgeniya", "Abramzon"],
+ ["Anne M", "Remes"],
+ ["Alice", "Kaganovich"],
+ ["Sonja W", "Scholz"],
+ ["Jamie", "Duckworth"],
+ ["Jinhui", "Ding"],
+ ["Daniel W", "Harmer"],
+ ["Dena G", "Hernandez"],
+ ["Janel O", "Johnson"],
+ ["Kin", "Mok"],
+ ["Mina", "Ryten"],
+ ["Danyah", "Trabzuni"],
+ ["Rita J", "Guerreiro"],
+ ["Richard W", "Orrell"],
+ ["James", "Neal"],
+ ["Alex", "Murray"],
+ ["Justin", "Pearson"],
+ ["Iris E", "Jansen"],
+ ["David", "Sondervan"],
+ ["Harro", "Seelaar"],
+ ["Derek", "Blake"],
+ ["Kate", "Young"],
+ ["Nicola", "Halliwell"],
+ ["Janis Bennion", "Callister"],
+ ["Greg", "Toulson"],
+ ["Anna", "Richardson"],
+ ["Alex", "Gerhard"],
+ ["Julie", "Snowden"],
+ ["David", "Mann"],
+ ["David", "Neary"],
+ ["Michael A", "Nalls"],
+ ["Terhi", "Peuralinna"],
+ ["Lilja", "Jansson"],
+ ["Veli-Matti", "Isoviita"],
+ ["Anna-Lotta", "Kaivorinne"],
+ ["Maarit", "H\u00f6ltt\u00e4-Vuori"],
+ ["Elina", "Ikonen"],
+ ["Raimo", "Sulkava"],
+ ["Michael", "Benatar"],
+ ["Joanne", "Wuu"],
+ ["Adriano", "Chi\u00f2"],
+ ["Gabriella", "Restagno"],
+ ["Giuseppe", "Borghero"],
+ ["Mario", "Sabatelli"],
+ ["David", "Heckerman"],
+ ["Ekaterina", "Rogaeva"],
+ ["Lorne", "Zinman"],
+ ["Jeffrey D", "Rothstein"],
+ ["Michael", "Sendtner"],
+ ["Carsten", "Drepper"],
+ ["Evan E", "Eichler"],
+ ["Can", "Alkan"],
+ ["Ziedulla", "Abdullaev"],
+ ["Svetlana D", "Pack"],
+ ["Amalia", "Dutra"],
+ ["Evgenia", "Pak"],
+ ["John", "Hardy"],
+ ["Andrew", "Singleton"],
+ ["Nigel M", "Williams"],
+ ["Peter", "Heutink"],
+ ["Stuart", "Pickering-Brown"],
+ ["Huw R", "Morris"],
+ ["Pentti J", "Tienari"],
+ ["Bryan J", "Traynor"]
+ ],
+ "publisher": "Neuron",
+ "issn": "1097-4199",
+ "date": "2011-09-21",
+ "abstract": "The chromosome 9p21 amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) locus contains one of the last major unidentified autosomal-dominant genes underlying these common neurodegenerative diseases. We have previously shown that a founder haplotype, covering the MOBKL2b, IFNK, and C9ORF72 genes, is present in the majority of cases linked to this region. Here we show that there is a large hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 on the affected haplotype. This repeat expansion segregates perfectly with disease in the Finnish population, underlying 46.0% of familial ALS and 21.1% of sporadic ALS in that population. Taken together with the D90A SOD1 mutation, 87% of familial ALS in Finland is now explained by a simple monogenic cause. The repeat expansion is also present in one-third of familial ALS cases of outbred European descent, making it the most common genetic cause of these fatal neurodegenerative diseases identified to date.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21944779"
+},
+{
+ "id": "pmid:9894797",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9894797",
+ "title": "Carrier detection in Duchenne and Becker muscular dystrophy Argentine families.",
+ "type": "article-journal",
+ "doi": "10.1111/j.1399-0004.1998.tb03771.x",
+ "authors": [
+ ["S E", "Baranzini"],
+ ["F", "Giliberto"],
+ ["V", "Dalamon"],
+ ["C", "Barreiro"],
+ ["M", "Garc\u00eda-Erro"],
+ ["J", "Grippo"],
+ ["I", "Szijan"]
+ ],
+ "publisher": "Clinical genetics",
+ "issn": "0009-9163",
+ "date": "1998-12-01",
+ "abstract": "In order to offer carrier detection, genetic counseling, and prenatal diagnosis to families with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) in our country, segregation analysis of highly polymorphic short tandem repeats (STR) (dC-dA)n: (dG-dT)n loci was utilized. The risks to females of 15 DMD BMD families (9 familial and 6 sporadic) were evaluated on STR, pedigree and serum creatine kinase (SCK) data. From the 36 females at risk of being carriers (not including 8 obligate carriers), results of STR analysis were compatible with carrier status in 7 and not compatible in 20. In 9 females, no information regarding carriership was derived from the STR analysis. Prenatal diagnosis is now possible on the carrier females. Previously identified deletions in the central part of the gene were confirmed by STR analysis in 3 families. Five new alleles were identified in Argentine individuals; allele frequencies differed from those of North American people. Results derived from this study are useful for carrier detection and genetic counseling in DMD/BMD. One case of probable mosaicism in an unaffected father was detected on a pedigree basis in a family with DMD patients.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9894797"
+},
+{
+ "id": "pmid:17877752",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17877752",
+ "title": "DMPK-associated myotonic dystrophy and CTG repeats in Alabama African Americans.",
+ "type": "article-journal",
+ "doi": "10.1111/j.1399-0004.2007.00883.x",
+ "authors": [
+ ["R T", "Acton"],
+ ["C A", "Rivers"],
+ ["B", "Watson"],
+ ["S J", "Oh"]
+ ],
+ "publisher": "Clinical genetics",
+ "issn": "0009-9163",
+ "date": "2007-09-17",
+ "abstract": "Myotonic dystrophy type 1 (DM1) is a result of a CTG expansion in the 3'-untranslated region of the DMPK gene. DM1 is rare among African blacks who have fewer large CTG repeats in the normal range than other racial/ethnic groups. Neither the prevalence of DM1 nor the relationship of CTG expansion to clinical status in African Americans (AAs) is well documented. We describe two AA brothers with DM1, each of whom had CTG repeats of 5/639; their father was reported to have DM1 and had CTG repeats of 5/60. Other family members had CTG repeats of 5-14. An unrelated AA patient from a second kinship also had DM1; an analysis revealed CTG repeats of 27/191. In 161 Alabama AA control subjects, we observed 18 CTG alleles from 5 to 28 repeats; the most common allele had five CTG repeats. The frequency of CTG repeats >or=15 were greater (p < 0.0003) in Pygmy, Amhara Ethiopian, Ashkenazi Jewish, North African Jewish, Israeli Muslim Arab, European white, and Japanese populations than in the Alabama AA population. These data suggest that the risk for DM1 in AAs is intermediate between that of African blacks and whites of European descent.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17877752"
+},
+{
+ "id": "pmid:27708271",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27708271",
+ "title": "Most Martin-Bell syndrome (FMR1-related disorder) Venezuelan patients did not show CGG expansion but instead display genetic heterogeneity.",
+ "type": "article-journal",
+ "doi": "10.1038/jhg.2016.114",
+ "authors": [
+ ["Yasser", "Vega"],
+ ["Sergio", "Arias"],
+ ["Irene", "Paradisi"]
+ ],
+ "publisher": "Journal of human genetics",
+ "issn": "1435-232X",
+ "date": "2016-10-06",
+ "abstract": "Martin-Bell syndrome is mainly caused by the expansion of CGG trinucleotide repeats (>200 CGG) in the first exon of the FMR1 gene, leading to hypermethylation of the promoter region and silencing of the FMR1 protein expression. These changes are responsible for a phenotype with varying degrees of mental retardation, a long face with large and protruding ears, macroorchidism and autistic behavior. There may also be, however, patients who exhibit typical features of the syndrome without any expansion in the FMR1 gene; thus, other mechanisms affecting the expression of the FMR1 gene were assessed in 25 out of 29 ascertained patients with the typical phenotype without full mutation. Promoter methylation status of FMR1, mutations in its sequence and copy number variations (CNVs) in genes associated with intellectual disability were investigated. In 25 independent male patients without expansion, the promoter region was unmethylated; one patient with a full mutation showed methylation mosaicism; and a female patient had 81.2% of CpG sites methylated and 18.8% hemimethylated. One heterozygous duplication in exon 6 of the PDCD6 gene (programmed cell death 6) and a heterozygous deletion in exon 5 of the CHL1 gene (cell adhesion molecule L1), respectively, were found in two independent patients.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27708271"
+},
+{
+ "id": "pmid:40084170",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/40084170",
+ "title": "A case report of oculopharyngodistal myopathy with 126 CGG repeat expansions in",
+ "type": "article-journal",
+ "doi": "10.3389/fgene.2025.1472907",
+ "authors": [
+ ["Wenjing", "Wang"],
+ ["Tielun", "Yin"],
+ ["Xinyu", "Zhang"],
+ ["Zhaoxia", "Wang"],
+ ["Tianyun", "Wang"],
+ ["Shuo", "Zhang"],
+ ["Yingshuang", "Zhang"],
+ ["Dongsheng", "Fan"]
+ ],
+ "publisher": "Frontiers in genetics",
+ "issn": "1664-8021",
+ "date": "2025-02-27",
+ "abstract": "Oculopharyngodistal myopathy (OPDM) is a rare hereditary muscle disease characterized by progressive ptosis, ophthalmoplegia, dysphagia, dysarthria, and distal muscle weakness. The genetic basis was identified in 2019 with CGG repeat expansions in the noncoding region of",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40084170"
+},
+{
+ "id": "pmid:37716514",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/37716514",
+ "title": "Aberrant splicing of mutant huntingtin in Huntington's disease knock-in pigs.",
+ "type": "article-journal",
+ "doi": "10.1016/j.nbd.2023.106291",
+ "authors": [
+ ["Huichun", "Tong"],
+ ["Tianqi", "Yang"],
+ ["Li", "Liu"],
+ ["Caijuan", "Li"],
+ ["Yize", "Sun"],
+ ["Qingqing", "Jia"],
+ ["Yiyang", "Qin"],
+ ["Laiqiang", "Chen"],
+ ["Xianxian", "Zhao"],
+ ["Gongke", "Zhou"],
+ ["Sen", "Yan"],
+ ["Xiao-Jiang", "Li"],
+ ["Shihua", "Li"]
+ ],
+ "publisher": "Neurobiology of disease",
+ "issn": "1095-953X",
+ "date": "2023-09-15",
+ "abstract": "Huntington's disease (HD) is an autosomal-dominant inherited neurodegenerative disease caused by a CAG repeat expansion in exon1 of the huntingtin gene (HTT). This expansion leads to the production of N-terminal mutant huntingtin protein (mHtt) that contains an expanded polyglutamine tract, which is toxic to neurons and causes neurodegeneration. While the production of N-terminal mHtt can be mediated by proteolytic cleavage of full-length mHtt, abnormal splicing of exon1-intron1 of mHtt has also been identified in the brains of HD mice and patients. However, the proportion of aberrantly spliced exon1 mHTT in relation to normal mHTT exon remains to be defined. In this study, HTT exon1 production was examined in the HD knock-in (KI) pig model, which more closely recapitulates neuropathology seen in HD patient brains than HD mouse models. The study revealed that aberrant spliced HTT exon1 is also present in the brains of HD pigs, but it is expressed at a much lower level than the normally spliced HTT exon products. These findings suggest that careful consideration is needed when assessing the contribution of aberrantly spliced mHTT exon1 to HD pathogenesis, and further rigorous investigation is required.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37716514"
+},
+{
+ "id": "pmid:35395816",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/35395816",
+ "title": "Tissue-specific and repeat length-dependent somatic instability of the X-linked dystonia parkinsonism-associated CCCTCT repeat.",
+ "type": "article-journal",
+ "doi": "10.1186/s40478-022-01349-0",
+ "authors": [
+ ["Lindsey N", "Campion"],
+ ["Alan", "Mejia Maza"],
+ ["Rachita", "Yadav"],
+ ["Ellen B", "Penney"],
+ ["Micaela G", "Murcar"],
+ ["Kevin", "Correia"],
+ ["Tammy", "Gillis"],
+ ["Cara", "Fernandez-Cerado"],
+ ["M Salvie", "Velasco-Andrada"],
+ ["G Paul", "Legarda"],
+ ["Niecy G", "Ganza-Bautista"],
+ ["J Benedict B", "Lagarde"],
+ ["Patrick J", "Acu\u00f1a"],
+ ["Trisha", "Multhaupt-Buell"],
+ ["Gabrielle", "Aldykiewicz"],
+ ["Melanie L", "Supnet"],
+ ["Jan K", "De Guzman"],
+ ["Criscely", "Go"],
+ ["Nutan", "Sharma"],
+ ["Edwin L", "Munoz"],
+ ["Mark C", "Ang"],
+ ["Cid Czarina E", "Diesta"],
+ ["D Cristopher", "Bragg"],
+ ["Laurie J", "Ozelius"],
+ ["Vanessa C", "Wheeler"]
+ ],
+ "publisher": "Acta neuropathologica communications",
+ "issn": "2051-5960",
+ "date": "2022-04-08",
+ "abstract": "X-linked dystonia-parkinsonism (XDP) is a progressive adult-onset neurodegenerative disorder caused by insertion of a SINE-VNTR-Alu (SVA) retrotransposon in the TAF1 gene. The SVA retrotransposon contains a CCCTCT hexameric repeat tract of variable length, whose length is inversely correlated with age at onset. This places XDP in a broader class of repeat expansion diseases, characterized by the instability of their causative repeat mutations. Here, we observe similar inverse correlations between CCCTCT repeat length with age at onset and age at death and no obvious correlation with disease duration. To gain insight into repeat instability in XDP we performed comprehensive quantitative analyses of somatic instability of the XDP CCCTCT repeat in blood and in seventeen brain regions from affected males. Our findings reveal repeat length-dependent and expansion-based instability of the XDP CCCTCT repeat, with greater levels of expansion in brain than in blood. The brain exhibits regional-specific patterns of instability that are broadly similar across individuals, with cerebellum exhibiting low instability and cortical regions exhibiting relatively high instability. The spectrum of somatic instability in the brain includes a high proportion of moderate repeat length changes of up to 5 repeats, as well as expansions of\u2009~\u200920-\u2009>\u2009100 repeats and contractions of\u2009~\u200920-40 repeats at lower frequencies. Comparison with HTT CAG repeat instability in postmortem Huntington's disease brains reveals similar brain region-specific profiles, indicating common trans-acting factors that contribute to the instability of both repeats. Analyses in XDP brains of expansion of a different SVA-associated CCCTCT located in the LIPG gene, and not known to be disease-associated, reveals repeat length-dependent expansion at overall lower levels relative to the XDP CCCTCT repeat, suggesting that expansion propensity may be modified by local chromatin structure. Together, the data support a role for repeat length-dependent somatic expansion in the process(es) driving the onset of XDP and prompt further investigation into repeat dynamics and the relationship to disease.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35395816"
+},
+{
+ "id": "pmid:35275350",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/35275350",
+ "title": "Investigation of the Influence of TBP CAG/CAA Repeats in Conjunction with HTT CAG Repeats on Huntington's Disease Age at Onset in a Brazilian Sample.",
+ "type": "article-journal",
+ "doi": "10.1007/s12031-021-01938-z",
+ "authors": [
+ ["Iane Dos Santos", "da Silva"],
+ ["Thays Andrade", "Apolin\u00e1rio"],
+ ["Luciana", "de Andrade Agostinho"],
+ ["Carmen Lucia Ant\u00e3o", "Paiva"]
+ ],
+ "publisher": "Journal of molecular neuroscience : MN",
+ "issn": "1559-1166",
+ "date": "2022-03-11",
+ "abstract": "Huntington's disease (HD) is a genetic neurodegenerative progressive and fatal disease characterized by motor disorder, cognitive impairment, and behavioral problems, caused by expanded repeats of CAG trinucleotides in the HTT gene. The aim of this study was to investigate the influence of TBP gene CAG/CAA repeats in conjunction with HTT gene CAG repeats, on the age at HD onset in Brazilian individuals. Individuals diagnosed as molecularly negative for HD presented 29-39 TBP CAG/CAA. Their most frequent allele had 36 repeats. In individuals diagnosed as molecularly positive for HD, a range of 25-40 TBP CAG/ CAA was found. The most frequent TBP allele had 38 repeats. We also conducted TBP direct Sanger sequencing of some samples which demonstrated other four TBP structures different from the basic TBP structure and others reported in the literature. The HTT expanded CAG and TBP CAG/CAA repeat sizes jointly explained 66% of the age at onset (AO) in our HD patients. The strongest variable in the model associated with AO was the number of expanded HTT CAG repeats. The difference between the association of HD AO with HTT expanded CAG together with TBP CAG/CAA and the association of HD AO with HTT expanded CAG was 0.001 (\u2206R",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35275350"
+},
+{
+ "id": "pmid:35058188",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/35058188",
+ "title": "Time-resolved FRET screening identifies small molecular modifiers of mutant Huntingtin conformational inflexibility in patient-derived cells.",
+ "type": "article-journal",
+ "doi": "10.1016/j.slasd.2021.10.005",
+ "authors": [
+ ["Johannes H", "Wilbertz"],
+ ["Julia", "Frappier"],
+ ["Sandra", "Muller"],
+ ["Sabine", "Gratzer"],
+ ["Walter", "Englaro"],
+ ["Lisa M", "Stanek"],
+ ["Barbara", "Calamini"]
+ ],
+ "publisher": "SLAS discovery : advancing life sciences R & D",
+ "issn": "2472-5560",
+ "date": "2021-10-10",
+ "abstract": "Huntington's disease (HD) is the most common monogenic neurodegenerative disease and is fatal. CAG repeat expansions in mutant Huntingtin (mHTT) exon 1\u00a0encode for polyglutamine (polyQ) stretches and influence age of onset and disease severity, depending on their length. mHTT is more structured compared to wild-type (wt) HTT, resulting in a decreased N-terminal conformational flexibility. mHTT inflexibility may contribute to both gain of function toxicity, due to increased mHTT aggregation propensity, but also to loss of function phenotypes, due to decreased interactions with binding partners. High-throughput-screening techniques to identify mHTT flexibility states and potential flexibility modifying small molecules are currently lacking. Here, we propose a novel approach for identifying small molecules that restore mHTT's conformational flexibility in human patient fibroblasts. We have applied a well-established antibody-based time-resolved F\u00f6rster resonance energy transfer (TR-FRET) immunoassay, which measures endogenous HTT flexibility using two validated HTT-specific antibodies, to a high-throughput screening platform. By performing a small-scale compound screen, we identified several small molecules that can partially rescue mHTT inflexibility, presumably by altering HTT post-translational modifications. Thus, we demonstrated that the HTT TR-FRET immunoassay can be miniaturized and applied to a compound screening workflow in patient cells. This automated assay can now be used in large screening campaigns to identify previously unknown HD drugs and drug targets.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35058188"
+},
+{
+ "id": "pmid:34880419",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/34880419",
+ "title": "Huntingtin structure is orchestrated by HAP40 and shows a polyglutamine expansion-specific interaction with exon 1.",
+ "type": "article-journal",
+ "doi": "10.1038/s42003-021-02895-4",
+ "authors": [
+ ["Rachel J", "Harding"],
+ ["Justin C", "Deme"],
+ ["Johannes F", "Hevler"],
+ ["Sem", "Tamara"],
+ ["Alexander", "Lemak"],
+ ["Jeffrey P", "Cantle"],
+ ["Magdalena M", "Szewczyk"],
+ ["Nola", "Begeja"],
+ ["Siobhan", "Goss"],
+ ["Xiaobing", "Zuo"],
+ ["Peter", "Loppnau"],
+ ["Alma", "Seitova"],
+ ["Ashley", "Hutchinson"],
+ ["Lixin", "Fan"],
+ ["Ray", "Truant"],
+ ["Matthieu", "Schapira"],
+ ["Jeffrey B", "Carroll"],
+ ["Albert J R", "Heck"],
+ ["Susan M", "Lea"],
+ ["Cheryl H", "Arrowsmith"]
+ ],
+ "publisher": "Communications biology",
+ "issn": "2399-3642",
+ "date": "2021-12-08",
+ "abstract": "Huntington's disease results from expansion of a glutamine-coding CAG tract in the huntingtin (HTT) gene, producing an aberrantly functioning form of HTT. Both wildtype and disease-state HTT form a hetero-dimer with HAP40 of unknown functional relevance. We demonstrate in vivo and in cell models that HTT and HAP40 cellular abundance are coupled. Integrating data from a 2.6\u2009\u00c5 cryo-electron microscopy structure, cross-linking mass spectrometry, small-angle X-ray scattering, and modeling, we provide a near-atomic-level view of HTT, its molecular interaction surfaces and compacted domain architecture, orchestrated by HAP40. Native mass\u00a0spectrometry reveals a remarkably stable hetero-dimer, potentially explaining the cellular inter-dependence of HTT and HAP40. The exon 1 region of HTT is dynamic but shows greater conformational variety in the polyglutamine expanded mutant than wildtype exon 1. Our data provide a foundation for future functional and drug discovery studies targeting Huntington's disease and illuminate the structural consequences of HTT polyglutamine expansion.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34880419"
+},
+{
+ "id": "pmid:34663519",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/34663519",
+ "title": "Reduced mitochondrial complex II activity enhances cell death via intracellular reactive oxygen species in STHdhQ111 striatal neurons with mutant huntingtin.",
+ "type": "article-journal",
+ "doi": "10.1016/j.jphs.2021.09.001",
+ "authors": [
+ ["Noria", "Okada"],
+ ["Tomohiro", "Yako"],
+ ["Shinsuke", "Nakamura"],
+ ["Masamitsu", "Shimazawa"],
+ ["Hideaki", "Hara"]
+ ],
+ "publisher": "Journal of pharmacological sciences",
+ "issn": "1347-8648",
+ "date": "2021-09-11",
+ "abstract": "Huntington's disease (HD) is an inherited neurodegenerative disorder caused by CAG repeat expansion in the huntingtin (HTT) gene. Here, we examined the effects of antioxidants on 3-nitropropionic acid (3-NP; a mitochondrial complex II inhibitor)-induced mitochondrial dysfunction and cell death in STHdhQ111 striatal cells carrying homozygous mutant HTT with extended CAG repeats compared with those in STHdhQ7 striatal cells. 3-NP reduced cell viability and increased cell death both in STHdhQ111 and STHdhQ7, and the cytotoxicity was markedly attenuated by antioxidants (N-acetyl-l-cysteine and edaravone). Furthermore, 3-NP increased intracellular reactive oxygen species (ROS) production in both cell lines, and this increase was inhibited by antioxidants. Mitochondrial ROS was also increased by 3-NP in STHdhQ111 but not in STHdhQ7, and this increase was significantly inhibited by edaravone. Mitochondrial membrane potential (MMP) was lower in STHdhQ111 than that in STHdhQ7, and antioxidants prevented 3-NP-induced MMP decrease in STHdhQ111.3-NP enhanced oligomerization of dynamin-related protein 1 (Drp1), a protein that promotes mitochondrial fission in both cells, and both antioxidants prevented the increase in oligomerization. These results suggest that reduced mitochondrial complex II activity enhances cell death via intracellular ROS production and Drp1 oligomerization in striatal cells with mutant HTT and antioxidants may reduce striatal cell death.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34663519"
+},
+{
+ "id": "pmid:34520257",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/34520257",
+ "title": "Oligonucleotides Targeting DNA Repeats Downregulate",
+ "type": "article-journal",
+ "doi": "10.1089/nat.2021.0021",
+ "authors": [
+ ["Tea", "Umek"],
+ ["Thomas", "Olsson"],
+ ["Olof", "Gissberg"],
+ ["Osama", "Saher"],
+ ["Eman M", "Zaghloul"],
+ ["Karin E", "Lundin"],
+ ["Jesper", "Wengel"],
+ ["Eric", "Hanse"],
+ ["Henrik", "Zetterberg"],
+ ["Dzeneta", "Vizlin-Hodzic"],
+ ["C I Edvard", "Smith"],
+ ["Rula", "Zain"]
+ ],
+ "publisher": "Nucleic acid therapeutics",
+ "issn": "2159-3345",
+ "date": "2021-09-13",
+ "abstract": "Huntington's disease (HD) is one of the most common, dominantly inherited neurodegenerative disorders. It affects the striatum, cerebral cortex, and other subcortical structures leading to involuntary movement abnormalities, emotional disturbances, and cognitive impairments. HD is caused by a CAG\u2022CTG trinucleotide-repeat expansion in exon 1 of the",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34520257"
+},
+{
+ "id": "pmid:34366363",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/34366363",
+ "title": "Subdural Hematoma as a Serious Complication of Huntington's Disease: An Observational Study.",
+ "type": "article-journal",
+ "doi": "10.3233/jhd-210478",
+ "authors": [
+ ["Marie", "Davis"],
+ ["Vicki", "Wheelock"],
+ ["Lauren", "Talman"],
+ ["Caitlin", "Latimer"],
+ ["Brenda", "Vicars"],
+ ["Anny", "Lin"],
+ ["Suman", "Jayadev"],
+ ["Thomas", "Bird"]
+ ],
+ "publisher": "Journal of Huntington's disease",
+ "issn": "1879-6400",
+ "date": "2021-01-01",
+ "abstract": "Persons with Huntington's disease (HD) are at increased risk for subdural hematomas (SDH) because of underlying brain atrophy and increased frequency of falls and head trauma. SDH can cause serious disability, but there is little information about the association of SDH with HD in the medical literature.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34366363"
+},
+{
+ "id": "pmid:34093422",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/34093422",
+ "title": "Ranking the Predictive Power of Clinical and Biological Features Associated With Disease Progression in Huntington's Disease.",
+ "type": "article-journal",
+ "doi": "10.3389/fneur.2021.678484",
+ "authors": [
+ ["Naghmeh", "Ghazaleh"],
+ ["Richard", "Houghton"],
+ ["Giuseppe", "Palermo"],
+ ["Scott A", "Schobel"],
+ ["Peter A", "Wijeratne"],
+ ["Jeffrey D", "Long"]
+ ],
+ "publisher": "Frontiers in neurology",
+ "issn": "1664-2295",
+ "date": "2021-05-20",
+ "abstract": "Huntington's disease (HD) is characterised by a triad of cognitive, behavioural, and motor symptoms which lead to functional decline and loss of independence. With potential disease-modifying therapies in development, there is interest in accurately measuring HD progression and characterising prognostic variables to improve efficiency of clinical trials. Using the large, prospective Enroll-HD cohort, we investigated the relative contribution and ranking of potential prognostic variables in patients with manifest HD. A random forest regression model was trained to predict change of clinical outcomes based on the variables, which were ranked based on their contribution to the prediction. The highest-ranked variables included novel predictors of progression-being accompanied at clinical visit, cognitive impairment, age at diagnosis and tetrabenazine or antipsychotics use-in addition to established predictors, cytosine adenine guanine (CAG) repeat length and CAG-age product. The novel prognostic variables improved the ability of the model to predict clinical outcomes and may be candidates for statistical control in HD clinical studies.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34093422"
},
{
- "id": "omim:309510",
- "manubot_success": false,
- "link": "https://omim.org/entry/309510",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/309510. Skipping"
+ "id": "pmid:33949657",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/33949657",
+ "title": "Lack of association of somatic CAG repeat expansion with striatal neurodegeneration in HD knock-in animal models.",
+ "type": "article-journal",
+ "doi": "10.1093/hmg/ddab129",
+ "authors": [
+ ["Dazhang", "Bai"],
+ ["Peng", "Yin"],
+ ["Yiran", "Zhang"],
+ ["Fengwei", "Sun"],
+ ["Laiqiang", "Chen"],
+ ["Li", "Lin"],
+ ["Sen", "Yan"],
+ ["Shihua", "Li"],
+ ["Xiao-Jiang", "Li"]
+ ],
+ "publisher": "Human molecular genetics",
+ "issn": "1460-2083",
+ "date": "2021-07-28",
+ "abstract": "Our previous work has established a huntingtin knock-in (KI) pig model that displays striatal neuronal loss, allowing us to examine if somatic CAG expansion in striatum accounts for the preferential neurodegeneration in Huntington disease (HD). We found that HD KI pigs do not display somatic CAG expansion in striatum as HD KI mice and that the majority of polyQ repeats in exon 1 HTT in the striatum of HD KI mice are fairly stable. We also found that striatal MSH2 and MLH3, which are involved in DNA repair, are more abundant in mouse brains than pig brains. Consistently inhibiting MSH2 and MLH3 reduced the somatic CAG expansion in HD KI mouse striatum with no influence on neuropathology. Our findings suggest that somatic CAG expansion is species-dependent, occurs in a small fraction of the HD gene in mice, and does not critically contribute to HD neuropathology.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33949657"
},
{
- "id": "omim:308350",
- "manubot_success": false,
- "link": "https://omim.org/entry/308350",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/308350. Skipping"
+ "id": "pmid:33751106",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/33751106",
+ "title": "Somatic CAG expansion in Huntington's disease is dependent on the MLH3 endonuclease domain, which can be excluded via splice redirection.",
+ "type": "article-journal",
+ "doi": "10.1093/nar/gkab152",
+ "authors": [
+ ["Jennie C L", "Roy"],
+ ["Antonia", "Vitalo"],
+ ["Marissa A", "Andrew"],
+ ["Eduarda", "Mota-Silva"],
+ ["Marina", "Kovalenko"],
+ ["Zoe", "Burch"],
+ ["Anh M", "Nhu"],
+ ["Paula E", "Cohen"],
+ ["Ed", "Grabczyk"],
+ ["Vanessa C", "Wheeler"],
+ ["Ricardo", "Mouro Pinto"]
+ ],
+ "publisher": "Nucleic acids research",
+ "issn": "1362-4962",
+ "date": "2021-04-19",
+ "abstract": "Somatic expansion of the CAG repeat tract that causes Huntington's disease (HD) is thought to contribute to the rate of disease pathogenesis. Therefore, factors influencing repeat expansion are potential therapeutic targets. Genes in the DNA mismatch repair pathway are critical drivers of somatic expansion in HD mouse models. Here, we have tested, using genetic and pharmacological approaches, the role of the endonuclease domain of the mismatch repair protein MLH3 in somatic CAG expansion in HD mice and patient cells. A point mutation in the MLH3 endonuclease domain completely eliminated CAG expansion in the brain and peripheral tissues of a HD knock-in mouse model (HttQ111). To test whether the MLH3 endonuclease could be manipulated pharmacologically, we delivered splice switching oligonucleotides in mice to redirect Mlh3 splicing to exclude the endonuclease domain. Splice redirection to an isoform lacking the endonuclease domain was associated with reduced CAG expansion. Finally, CAG expansion in HD patient-derived primary fibroblasts was also significantly reduced by redirecting MLH3 splicing to the endogenous endonuclease domain-lacking isoform. These data indicate the potential of targeting the MLH3 endonuclease domain to slow somatic CAG repeat expansion in HD, a therapeutic strategy that may be applicable across multiple repeat expansion disorders.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33751106"
},
{
- "id": "omim:300004",
- "manubot_success": false,
- "link": "https://omim.org/entry/300004",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/300004. Skipping"
+ "id": "pmid:33611676",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/33611676",
+ "title": "CAG repeat instability in embryonic stem cells and derivative spermatogenic cells of transgenic Huntington's disease monkey.",
+ "type": "article-journal",
+ "doi": "10.1007/s10815-021-02106-3",
+ "authors": [
+ ["Sujittra", "Khampang"],
+ ["Rangsun", "Parnpai"],
+ ["Wiriya", "Mahikul"],
+ ["Charles A", "Easley"],
+ ["In Ki", "Cho"],
+ ["Anthony W S", "Chan"]
+ ],
+ "publisher": "Journal of assisted reproduction and genetics",
+ "issn": "1573-7330",
+ "date": "2021-02-20",
+ "abstract": "The expansion of CAG (glutamine; Q) trinucleotide repeats (TNRs) predominantly occurs through male lineage in Huntington's disease (HD). As a result, offspring will have larger CAG repeats compared to their fathers, which causes an earlier onset of the disease called genetic anticipation. This study aims to develop a novel in vitro model to replicate CAG repeat instability in early spermatogenesis and demonstrate the biological process of genetic anticipation by using the HD stem cell model for the first time.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33611676"
},
{
- "id": "omim:300215",
- "manubot_success": false,
- "link": "https://omim.org/entry/300215",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/300215. Skipping"
+ "id": "pmid:33547932",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/33547932",
+ "title": "Huntington's disease brain-derived small RNAs recapitulate associated neuropathology in mice.",
+ "type": "article-journal",
+ "doi": "10.1007/s00401-021-02272-9",
+ "authors": [
+ ["Jordi", "Creus-Muncunill"],
+ ["Anna", "Guisado-Corcoll"],
+ ["Veronica", "Venturi"],
+ ["Lorena", "Pantano"],
+ ["Georgia", "Escaram\u00eds"],
+ ["Marta", "Garc\u00eda de Herreros"],
+ ["Maria", "Solaguren-Beascoa"],
+ ["Ana", "G\u00e1mez-Valero"],
+ ["Cristina", "Navarrete"],
+ ["Merc\u00e8", "Masana"],
+ ["Franc", "Llorens"],
+ ["Daniela", "Diaz-Lucena"],
+ ["Esther", "P\u00e9rez-Navarro"],
+ ["Eul\u00e0lia", "Mart\u00ed"]
+ ],
+ "publisher": "Acta neuropathologica",
+ "issn": "1432-0533",
+ "date": "2021-02-06",
+ "abstract": "Progressive motor alterations and selective death of striatal medium spiny neurons (MSNs) are key pathological hallmarks of Huntington's disease (HD), a neurodegenerative condition caused by a CAG trinucleotide repeat expansion in the coding region of the huntingtin (HTT) gene. Most research has focused on the pathogenic effects of the resultant protein product(s); however, growing evidence indicates that expanded CAG repeats within mutant HTT mRNA and derived small CAG repeat RNAs (sCAG) participate in HD pathophysiology. The individual contribution of protein versus RNA toxicity to HD pathophysiology remains largely uncharacterized and the role of other classes of small RNAs (sRNA) that are strongly perturbed in HD is uncertain. Here, we demonstrate that sRNA produced in the putamen of HD patients (HD-sRNA-PT) are sufficient to induce HD pathology in vivo. Mice injected with HD-sRNA-PT show motor abnormalities, decreased levels of striatal HD-related proteins, disruption of the indirect pathway, and strong transcriptional abnormalities, paralleling human HD pathology. Importantly, we show that the specific blockage of sCAG mitigates HD-sRNA-PT neurotoxicity only to a limited extent. This observation prompted us to identify other sRNA species enriched in HD putamen with neurotoxic potential. We detected high levels of tRNA fragments (tRFs) in HD putamen, and we validated the neurotoxic potential of an Alanine derived tRF in vitro. These results highlight that HD-sRNA-PT are neurotoxic, and suggest that multiple sRNA species contribute to striatal dysfunction and general transcriptomic changes, favoring therapeutic strategies based on the blockage of sRNA-mediated toxicity.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33547932"
},
{
- "id": "omim:183090",
- "manubot_success": false,
- "link": "https://omim.org/entry/183090",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/183090. Skipping"
+ "id": "pmid:33249136",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/33249136",
+ "title": "An integrated metagenomics and metabolomics approach implicates the microbiota-gut-brain axis in the pathogenesis of Huntington's disease.",
+ "type": "article-journal",
+ "doi": "10.1016/j.nbd.2020.105199",
+ "authors": [
+ ["Geraldine", "Kong"],
+ ["Susan", "Ellul"],
+ ["Vinod K", "Narayana"],
+ ["Komal", "Kanojia"],
+ ["Harvey Tran Thai", "Ha"],
+ ["Shanshan", "Li"],
+ ["Thibault", "Renoir"],
+ ["Kim-Anh L\u00ea", "Cao"],
+ ["Anthony J", "Hannan"]
+ ],
+ "publisher": "Neurobiology of disease",
+ "issn": "1095-953X",
+ "date": "2020-11-26",
+ "abstract": "Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder with onset and severity of symptoms influenced by various environmental factors. Recent discoveries have highlighted the importance of the gastrointestinal microbiome in mediating the gut-brain-axis bidirectional communication via circulating factors. Using shotgun sequencing, we investigated the gut microbiome composition in the R6/1 transgenic mouse model of HD from 4 to 12\u00a0weeks of age (early adolescent through to adult stages). Targeted metabolomics was also performed on the blood plasma of these mice (n\u00a0=\u00a09 per group) at 12\u00a0weeks of age to investigate potential effects of gut dysbiosis on the plasma metabolome profile.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33249136"
},
{
- "id": "omim:164500",
- "manubot_success": false,
- "link": "https://omim.org/entry/164500",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/164500. Skipping"
+ "id": "pmid:32979842",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/32979842",
+ "title": "Structural brain correlates of dementia in Huntington's disease.",
+ "type": "article-journal",
+ "doi": "10.1016/j.nicl.2020.102415",
+ "authors": [
+ ["Saul", "Martinez-Horta"],
+ ["Frederic", "Sampedro"],
+ ["Andrea", "Horta-Barba"],
+ ["Jes\u00fas", "Perez-Perez"],
+ ["Javier", "Pagonabarraga"],
+ ["Beatriz", "Gomez-Anson"],
+ ["Jaime", "Kulisevsky"]
+ ],
+ "publisher": "NeuroImage. Clinical",
+ "issn": "2213-1582",
+ "date": "2020-09-09",
+ "abstract": "Huntington's disease (HD) is a fatal genetic neurodegenerative disorder with no effective treatment currently available. Progressive basal ganglia and whole-brain atrophy and concurrent cognitive deterioration are prototypical aspects of HD. However, the specific patterns of brain atrophy underlying cognitive impairment of different severity in HD are poorly understood. The aim of this study was to investigate the specific structural brain correlates of major cognitive deficits in HD and to explore its association with neuropsychological indicators.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32979842"
},
{
- "id": "omim:608768",
- "manubot_success": false,
- "link": "https://omim.org/entry/608768",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/608768. Skipping"
+ "id": "pmid:32979507",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/32979507",
+ "title": "Inconsistencies in histone acetylation patterns among different HD model systems and HD post-mortem brains.",
+ "type": "article-journal",
+ "doi": "10.1016/j.nbd.2020.105092",
+ "authors": [
+ ["Pritika", "Narayan"],
+ ["Suzanne", "Reid"],
+ ["Emma L", "Scotter"],
+ ["Ailsa L", "McGregor"],
+ ["Nasim F", "Mehrabi"],
+ ["Malvindar K", "Singh-Bains"],
+ ["Michelle", "Glass"],
+ ["Richard L M", "Faull"],
+ ["Russell G", "Snell"],
+ ["Mike", "Dragunow"]
+ ],
+ "publisher": "Neurobiology of disease",
+ "issn": "1095-953X",
+ "date": "2020-09-23",
+ "abstract": "Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in exon 1 of the huntingtin gene. Emerging evidence shows that additional epigenetic factors can modify disease phenotypes. Harnessing the ability of the epigenome to modify the disease for therapeutic purposes is therefore of interest. Epigenome modifiers, such as histone deacetylase inhibitors (HDACi), have improved pathology in a range of HD models. Yet in clinical trials, HDACi have failed to alleviate HD symptoms in patients. This study investigated potential reasons for the lack of translation of the therapeutic benefits of HDACi from lab to clinic. We analysed histone acetylation patterns of immuno-positive nuclei from brain sections and tissue microarrays from post-mortem human control and HD cases alongside several well-established HD models (OVT73 transgenic HD sheep, YAC128 mice, and an in vitro cell model expressing 97Q mutant huntingtin). Significant increases in histone H4 acetylation were observed in post-mortem HD cases, OVT73 transgenic HD sheep and in vitro models; these changes were absent in YAC128 mice. In addition, nuclear labelling for acetyl-histone H4 levels were inversely proportional to mutant huntingtin aggregate load in HD human cortex. Our data raise concerns regarding the utility of HDACi for the treatment of HD when regions of pathology exhibit already elevated histone acetylation patterns and emphasize the importance of searching for alternative epigenetic targets in future therapeutic strategies aiming to rescue HD phenotypes.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32979507"
},
{
- "id": "omim:117210",
- "manubot_success": false,
- "link": "https://omim.org/entry/117210",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/117210. Skipping"
+ "id": "pmid:32825467",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/32825467",
+ "title": "The Association between CAG Repeat Length and Age of Onset of Juvenile-Onset Huntington's Disease.",
+ "type": "article-journal",
+ "doi": "10.3390/brainsci10090575",
+ "authors": [
+ ["Jordan L", "Schultz"],
+ ["Amelia D", "Moser"],
+ ["Peg C", "Nopoulos"]
+ ],
+ "publisher": "Brain sciences",
+ "issn": "2076-3425",
+ "date": "2020-08-20",
+ "abstract": "There is a known negative association between cytosine-adenine-guanine (CAG) repeat length and the age of motor onset (AMO) in adult-onset Huntington's Disease (AOHD). This relationship is less clear in patients with juvenile-onset Huntington's disease (JOHD), however, given the rarity of this patient population. The aim of this study was to investigate this relationship amongst a relatively large group of patients with JOHD using data from the Kids-JOHD study. Additionally, we analyzed data from the Enroll-HD platform and the Predict-HD study to compare the relationship between CAG repeat length and AMO amongst patients with AOHD to that amongst patients with JOHD using linear regression models. In line with previous reports, the variance in AMO that was predicted by CAG repeat length was 59% (",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32825467"
+},
+{
+ "id": "pmid:32612964",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/32612964",
+ "title": "Polymorphisms of SLC19A1 80 G>A, MTHFR 677 C>T, and Tandem TS Repeats Influence Pharmacokinetics, Acute Liver Toxicity, and Vomiting in Children With Acute Lymphoblastic Leukemia Treated With High Doses of Methotrexate.",
+ "type": "article-journal",
+ "doi": "10.3389/fped.2020.00307",
+ "authors": [
+ ["Magdalena", "Cwiklinska"],
+ ["Malgorzata", "Czogala"],
+ ["Kinga", "Kwiecinska"],
+ ["Anna", "Madetko-Talowska"],
+ ["Malgorzata", "Szafarz"],
+ ["Katarzyna", "Pawinska"],
+ ["Aleksandra", "Wieczorek"],
+ ["Tomasz", "Klekawka"],
+ ["Magdalena", "Rej"],
+ ["Konrad", "Stepien"],
+ ["Przemyslaw", "Halubiec"],
+ ["Agnieszka", "Lazarczyk"],
+ ["Karol", "Miklusiak"],
+ ["Miroslaw", "Bik-Multanowski"],
+ ["Walentyna", "Balwierz"],
+ ["Szymon", "Skoczen"]
+ ],
+ "publisher": "Frontiers in pediatrics",
+ "issn": "2296-2360",
+ "date": "2020-06-16",
+ "abstract": "",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32612964"
},
{
- "id": "omim:105500",
- "manubot_success": false,
- "link": "https://omim.org/entry/105500",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/105500. Skipping"
+ "id": "pmid:32424160",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/32424160",
+ "title": "Co-chaperones DNAJA1 and DNAJB6 are critical for regulation of polyglutamine aggregation.",
+ "type": "article-journal",
+ "doi": "10.1038/s41598-020-65046-5",
+ "authors": [
+ ["Claudio", "Rodr\u00edguez-Gonz\u00e1lez"],
+ ["Shiying", "Lin"],
+ ["Sertan", "Arkan"],
+ ["Christian", "Hansen"]
+ ],
+ "publisher": "Scientific reports",
+ "issn": "2045-2322",
+ "date": "2020-05-18",
+ "abstract": "Huntington's disease (HD) is caused by CAG repeat expansion in the huntingtin gene. The expanded polyglutamine (polyQ) repeat of the encoded protein leads to protein misfolding and aggregation, resulting in increased neuronal cell death. DNAJ co-chaperones play a crucial role in transferring misfolded/unfolded proteins to HSP70 chaperones, which play an essential role for protein folding. Here, we investigated the effect of knock out (KO) of three individual DNAJ genes in HEK293 cells expressing polyglutamine74exon1 huntingtin (polyQ74htt). Flourescence\u00a0microscopy analysis revealed that KO of DNAJB6 resulted in a 5-fold increase in polyQ74htt aggregation and that DNAJA1 KO resulted in a 4-fold decrease of polyQ74htt aggregation. KO of DNAJB1 did not change the propensity of polyQ74htt to aggregate in cells. These findings where confirmed both by fluorescence microscopy analysis and filter trap assay (FTA). DNAJB6 KO cells displayed an increased rate of cell death as assessed by trypan blue exclusion and propidium iodide (PI) uptake assays. These results demonstrate that the DNAJ proteins DNAJA1 and DNAJB6 can modulate polyQ aggregation in opposite manners, and thus that fine-tuning the cellular levels of DNAJ proteins is critical for suppression of polyQ aggregation and cell survival.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32424160"
},
{
- "id": "omim:147791",
- "manubot_success": false,
- "link": "https://omim.org/entry/147791",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/147791. Skipping"
+ "id": "pmid:32102602",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/32102602",
+ "title": "Alcohol Use, Mental Health, and Functional Capacity as Predictors of Workplace Disability in a Cohort With Manifest Huntington's Disease.",
+ "type": "article-journal",
+ "doi": "10.1176/appi.neuropsych.19090199",
+ "authors": [
+ ["Anita M Y", "Goh"],
+ ["Emily", "You"],
+ ["Stephanie", "Perin"],
+ ["Nicola T", "Lautenschlager"],
+ ["Fiona J", "Clay"],
+ ["Samantha M", "Loi"],
+ ["Terence", "Chong"],
+ ["David", "Ames"],
+ ["Edmond", "Chiu"],
+ ["Kathryn A", "Ellis"]
+ ],
+ "publisher": "The Journal of neuropsychiatry and clinical neurosciences",
+ "issn": "1545-7222",
+ "date": "2020-02-27",
+ "abstract": "Huntington's disease (HD) is an inherited neurodegenerative disease involving motor, cognitive, psychiatric, and behavioral impairments that eventually affect work-role functioning. There is limited research regarding predictors of workplace disability in HD. The authors examined predictors of work impairment and disability in a cross-sectional cohort of employed persons with symptomatic HD participating in the worldwide Enroll-HD study.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32102602"
},
{
- "id": "omim:615945",
- "manubot_success": false,
- "link": "https://omim.org/entry/615945",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/615945. Skipping"
+ "id": "pmid:31893246",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/31893246",
+ "title": "Preimplantation genetic testing for Huntington disease: the perspective of one Portuguese center.",
+ "type": "article-journal",
+ "doi": "10.1097/j.pbj.0000000000000048",
+ "authors": [
+ ["Diogo", "Ferreira"],
+ ["Berta", "Carvalho"],
+ ["Ana P", "Neto"],
+ ["Joaquina", "Silva"],
+ ["Ana M", "P\u00f3voa"],
+ ["Alberto", "Barros"],
+ ["Filipa", "Carvalho"]
+ ],
+ "publisher": "Porto biomedical journal",
+ "issn": "2444-8672",
+ "date": "2019-09-04",
+ "abstract": "Huntington disease (HD) is an autosomal dominant late-onset neurodegenerative disease caused by an unstable cytosine-adenine-guanine trinucleotide repeat expansion in the huntingtin (",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31893246"
},
{
- "id": "omim:136630",
- "manubot_success": false,
- "link": "https://omim.org/entry/136630",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/136630. Skipping"
+ "id": "pmid:31844074",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/31844074",
+ "title": "Assessing average somatic CAG repeat instability at the protein level.",
+ "type": "article-journal",
+ "doi": "10.1038/s41598-019-55202-x",
+ "authors": [
+ ["Hubert", "Aviolat"],
+ ["Ricardo Mouro", "Pinto"],
+ ["Elizabeth", "Godschall"],
+ ["Ryan", "Murtha"],
+ ["Hannah E", "Richey"],
+ ["Ellen", "Sapp"],
+ ["Petr", "Vodicka"],
+ ["Vanessa C", "Wheeler"],
+ ["Kimberly B", "Kegel-Gleason"],
+ ["Marian", "DiFiglia"]
+ ],
+ "publisher": "Scientific reports",
+ "issn": "2045-2322",
+ "date": "2019-12-16",
+ "abstract": "Sandwich ELISA-based methods use Abs that target the expanded polyglutamine (polyQ) tract to quantify mutant huntingtin (mHTT). Using Meso Scale Discovery\u00a0(MSD) assay, the mHTT signal detected with MW1 Ab correlated with polyQ length and doubled with a difference of only 7 glutamine residues between equivalent amounts of purified mHTTexon1 proteins. Similar polyQ length-dependent effects on MSD signals were confirmed using endogenous full length mHTT from brains of Huntington's disease (HD) knock-in (KI) mice. We used this avidity bias to devise a method to assess average CAG repeat instability at the protein level in a mixed population of HTT proteins present in tissues. Signal detected for average polyQ length quantification at the protein level by our method exhibited a strong correlation with average CAG repeat length at the genomic DNA level determined by PCR method in striatal tissue homogenates from Hdh",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31844074"
},
{
- "id": "omim:229300",
- "manubot_success": false,
- "link": "https://omim.org/entry/229300",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/229300. Skipping"
+ "id": "pmid:31728006",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/31728006",
+ "title": "Discovery of a potent small molecule inhibiting Huntington's disease\u00a0(HD) pathogenesis via targeting CAG repeats RNA and Poly Q protein.",
+ "type": "article-journal",
+ "doi": "10.1038/s41598-019-53410-z",
+ "authors": [
+ ["Eshan", "Khan"],
+ ["Subodh Kumar", "Mishra"],
+ ["Ribhav", "Mishra"],
+ ["Amit", "Mishra"],
+ ["Amit", "Kumar"]
+ ],
+ "publisher": "Scientific reports",
+ "issn": "2045-2322",
+ "date": "2019-11-14",
+ "abstract": "CAG repeats RNA causes various fatal neurodegenerative diseases exemplified by Huntington's disease (HD) and several spinocerebellar ataxias (SCAs). Although there are differences in the pathogenic mechanisms, these diseases share the common cause, i.e., expansion of CAG repeats. The shared cause of these diseases raises the possibility for the exploiting the common target as a potential therapeutic approach. Oligonucleotide-based therapeutics are designed earlier with the help of the base pairing rule but are not very promiscuous, considering the nonspecific stimulation of the immune system and the poor cellular delivery. Therefore, small molecules-based therapeutics are preferred for targeting the repeats expansion disorders. Here, we have used the chemical similarity search approach to discern the small molecules that selectively target toxic CAG RNA. The lead compounds showed the specificity towards AA mismatch in biophysical studies including CD, ITC, and NMR spectroscopy and thus aided to forestall the polyQ mediated pathogenicity. Furthermore, the lead compounds also explicitly alleviate the polyQ mediated toxicity in HD cell models and patient-derived cells. These findings suggest that the lead compound could act as a chemical probe for AA mismatch containing RNA as well as plays a neuroprotective role in fatal neurodegenerative diseases like HD and SCAs.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31728006"
},
{
- "id": "omim:618940",
- "manubot_success": false,
- "link": "https://omim.org/entry/618940",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/618940. Skipping"
+ "id": "pmid:31722751",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/31722751",
+ "title": "Chromatin accessibility and transcription dynamics during in vitro astrocyte differentiation of Huntington's Disease Monkey pluripotent stem cells.",
+ "type": "article-journal",
+ "doi": "10.1186/s13072-019-0313-6",
+ "authors": [
+ ["Alexandra V", "Goodnight"],
+ ["Isaac", "Kremsky"],
+ ["Sujittra", "Khampang"],
+ ["Yoon Hee", "Jung"],
+ ["James M", "Billingsley"],
+ ["Steven E", "Bosinger"],
+ ["Victor G", "Corces"],
+ ["Anthony W S", "Chan"]
+ ],
+ "publisher": "Epigenetics & chromatin",
+ "issn": "1756-8935",
+ "date": "2019-11-13",
+ "abstract": "Huntington's Disease (HD) is a fatal neurodegenerative disorder caused by a CAG repeat expansion, resulting in a mutant huntingtin protein. While it is now clear that astrocytes are affected by HD and significantly contribute to neuronal dysfunction and pathogenesis, the alterations in the transcriptional and epigenetic profiles in HD astrocytes have yet to be characterized. Here, we examine global transcription and chromatin accessibility dynamics during in vitro astrocyte differentiation in a transgenic non-human primate model of HD.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31722751"
},
{
- "id": "omim:618412",
- "manubot_success": false,
- "link": "https://omim.org/entry/618412",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/618412. Skipping"
+ "id": "pmid:31599037",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/31599037",
+ "title": "Expanded polyglutamine impairs normal nuclear distribution of fused in sarcoma and poly (rC)-binding protein 1 in Huntington's disease.",
+ "type": "article-journal",
+ "doi": "10.1111/neup.12600",
+ "authors": [
+ ["Shinichiro", "Mori"],
+ ["Hiroyuki", "Honda"],
+ ["Takashi", "Ishii"],
+ ["Motoi", "Yoshimura"],
+ ["Naokazu", "Sasagasako"],
+ ["Satoshi O", "Suzuki"],
+ ["Takayuki", "Taniwaki"],
+ ["Toru", "Iwaki"]
+ ],
+ "publisher": "Neuropathology : official journal of the Japanese Society of Neuropathology",
+ "issn": "1440-1789",
+ "date": "2019-10-09",
+ "abstract": "Huntington's disease (HD) is an inherited neurodegenerative disease caused by a polyglutamine repeat expansion in the huntingtin protein. Immunohistochemical studies using the 1C2 antibody for polyglutamine expansion have detected characteristic intranuclear inclusions (INIs) in affected neurons in HD. Further, in vitro and mouse models of HD have shown that the INIs recruit several proteins relating to RNA splicing and translation. In the present study, we immunohistochemically investigated the association of INIs with various heterogeneous nuclear ribonucleoproteins in the cerebral cortex of four autopsy cases of HD. Fused in sarcoma (FUS) was colocalized with 1C2-positive nuclear inclusions in all examined cases. Localization of poly (rC)-binding protein 1 (PCBP1) in 1C2-positive nuclear inclusions was also observed. Double immunofluorescence revealed complete or partial loss of the normal, diffuse nuclear distribution of FUS or PCBP1 in neurons with 1C2-positive nuclear inclusions. This maldistribution of FUS in cortical neurons suggests a severe disturbance of messenger RNA processing, which may be a common pathogenetic mechanism of FUS-related familial amyotrophic lateral sclerosis.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31599037"
},
{
- "id": "omim:186000",
- "manubot_success": false,
- "link": "https://omim.org/entry/186000",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/186000. Skipping"
+ "id": "pmid:31586340",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/31586340",
+ "title": "Tracking Expansions of Stable and Threshold Length Trinucleotide Repeat Tracts In Vivo and In Vitro Using Saccharomyces cerevisiae.",
+ "type": "article-journal",
+ "doi": "10.1007/978-1-4939-9784-8_3",
+ "authors": [
+ ["Gregory M", "Williams"],
+ ["Athena K", "Petrides"],
+ ["Lata", "Balakrishnan"],
+ ["Jennifer A", "Surtees"]
+ ],
+ "publisher": "Methods in molecular biology (Clifton, N.J.)",
+ "issn": "1940-6029",
+ "date": "2020-01-01",
+ "abstract": "Trinucleotide repeat (TNR) tracts are inherently unstable during DNA replication, leading to repeat expansions and/or contractions. Expanded tracts are the cause of over 40 neurodegenerative and neuromuscular diseases. In this chapter, we focus on the (CAG)",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31586340"
},
{
- "id": "omim:164310",
- "manubot_success": false,
- "link": "https://omim.org/entry/164310",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/164310. Skipping"
+ "id": "pmid:31403680",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/31403680",
+ "title": "Association of CAG Repeats With Long-term Progression in Huntington Disease.",
+ "type": "article-journal",
+ "doi": "10.1001/jamaneurol.2019.2368",
+ "authors": [
+ ["Douglas R", "Langbehn"],
+ ["Julie C", "Stout"],
+ ["Sarah", "Gregory"],
+ ["James A", "Mills"],
+ ["Alexandra", "Durr"],
+ ["Blair R", "Leavitt"],
+ ["Raymund A C", "Roos"],
+ ["Jeffrey D", "Long"],
+ ["Gail", "Owen"],
+ ["Hans J", "Johnson"],
+ ["Beth", "Borowsky"],
+ ["David", "Craufurd"],
+ ["Ralf", "Reilmann"],
+ ["G Bernhard", "Landwehrmeyer"],
+ ["Rachael I", "Scahill"],
+ ["Sarah J", "Tabrizi"]
+ ],
+ "publisher": "JAMA neurology",
+ "issn": "2168-6157",
+ "date": "2019-11-01",
+ "abstract": "In Huntington disease (HD), mutation severity is defined by the length of the CAG trinucleotide sequence, a well-known predictor of clinical onset age. The association with disease trajectory is less well characterized. Quantifiable summary measures of trajectory applicable over decades of early disease progression are lacking. An accurate model of the age-CAG association with early progression is critical to clinical trial design, informing both sample size and intervention timing.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31403680"
},
{
- "id": "omim:613608",
- "manubot_success": false,
- "link": "https://omim.org/entry/613608",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/613608. Skipping"
+ "id": "pmid:31379510",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/31379510",
+ "title": "The Onset and Progression of Hippocampal Synaptic Plasticity Deficits in the Q175FDN Mouse Model of Huntington Disease.",
+ "type": "article-journal",
+ "doi": "10.3389/fncel.2019.00326",
+ "authors": [
+ ["Jade G", "Quirion"],
+ ["Matthew P", "Parsons"]
+ ],
+ "publisher": "Frontiers in cellular neuroscience",
+ "issn": "1662-5102",
+ "date": "2019-07-17",
+ "abstract": "Huntington disease (HD) is an inherited neurodegenerative disease characterized by a clinical triad of motor, psychiatric and cognitive symptoms. HD is caused by a CAG repeat expansion in the gene encoding the huntingtin protein. Homozygosity for the HD-causing mutation is extremely rare; thus, the majority of HD patients express the mutant huntingtin protein in addition to reduced levels of the non-pathogenic huntingtin protein. Deficits in synaptic plasticity, including hippocampal long-term potentiation (LTP), have been identified in various mouse models of HD and are thought to contribute to the debilitating cognitive symptoms associated with the disease. However, the bulk of these studies used N-terminal fragment or homozygous knock-in mouse models of HD at symptomatic ages, and our understanding of the onset and progression of synaptic plasticity deficits in the HD brain is lacking. To better understand the time-course of synaptic plasticity deficits in HD, as well as the impact of heterozygous and homozygous huntingtin mutations, we quantified basal synaptic connectivity, presynaptic release probability, presynaptically mediated post-tetanic potentiation (PTP) and postsynaptically mediated LTP at presymptomatic, early symptomatic and late symptomatic ages in heterozygous and homozygous Q175FDN knock-in HD mice. Our results demonstrate clear age-dependent effects of the HD-causing mutation on both short and long-term plasticity that generally emerge earlier in homozygous mice. Interestingly, deficits in presynaptic short-term plasticity were more closely linked to disease progression than deficits in postsynaptic LTP, and heterozygous mice were more susceptible to an LTP deficit when induced by high frequency stimulation compared to theta burst stimulation. To the best of our knowledge, the present study represents the most thorough characterization to date of the onset and progression of hippocampal synaptic plasticity deficits in a mouse model of HD, and should prove valuable to future studies exploring cellular mechanisms underlying the debilitating cognitive decline in HD.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31379510"
},
{
- "id": "omim:609893",
- "manubot_success": false,
- "link": "https://omim.org/entry/609893",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/609893. Skipping"
+ "id": "pmid:31108174",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/31108174",
+ "title": "Pridopidine protects neurons from mutant-huntingtin toxicity via the sigma-1 receptor.",
+ "type": "article-journal",
+ "doi": "10.1016/j.nbd.2019.05.009",
+ "authors": [
+ ["Chelsy R", "Eddings"],
+ ["Nicolas", "Arbez"],
+ ["Sergey", "Akimov"],
+ ["Michal", "Geva"],
+ ["Michael R", "Hayden"],
+ ["Christopher A", "Ross"]
+ ],
+ "publisher": "Neurobiology of disease",
+ "issn": "1095-953X",
+ "date": "2019-05-17",
+ "abstract": "Huntington's disease (HD) is a neurodegenerative disease caused by a CAG repeat expansion in the Huntingtin gene (HTT), translated into a Huntingtin protein with a polyglutamine expansion. There is preferential loss of medium spiny neurons within the striatum and cortical pyramidal neurons. Pridopidine is a small molecule showing therapeutic potential in HD preclinical and clinical studies. Pridopidine has nanomolar affinity to the sigma-1 receptor (sigma-1R), which is located predominantly at the endoplasmic reticulum (ER) and mitochondrial associated ER membrane, and activates neuroprotective pathways. Here we evaluate the neuroprotective effects of pridopidine against mutant Huntingtin toxicity in mouse and human derived in vitro cell models. We also investigate the involvement of the sigma-1 receptor in the mechanism of pridopidine. Pridopidine protects mutant Huntingtin transfected mouse primary striatal and cortical neurons, with an EC50 in the mid nanomolar range, as well as HD patient-derived induced pluripotent stem cells (iPSCs). This protection by pridopidine is blocked by NE-100, a purported sigma-1 receptor antagonist, and not blocked by ANA-12, a reported TrkB receptor antagonist. 3PPP, a documented sigma-1 receptor agonist, shows similar neuroprotective effects. Genetic knock out of the sigma-1 receptor dramatically decreases protection from pridopidine and 3PPP, but not protection via brain derived neurotrophic factor (BDNF). The neuroprotection afforded by pridopidine in our HD cell models is robust and sigma-1 receptor dependent. These studies support the further development of pridopidine, and other sigma-1 receptor agonists as neuroprotective agents for HD and perhaps for other disorders.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31108174"
},
{
- "id": "omim:105400",
- "manubot_success": false,
- "link": "https://omim.org/entry/105400",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/105400. Skipping"
+ "id": "pmid:31103960",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/31103960",
+ "title": "Clinical phenotype in carriers of intermediate alleles in the huntingtin gene.",
+ "type": "article-journal",
+ "doi": "10.1016/j.jns.2019.05.010",
+ "authors": [
+ ["Daniel", "Savitt"],
+ ["Joseph", "Jankovic"]
+ ],
+ "publisher": "Journal of the neurological sciences",
+ "issn": "1878-5883",
+ "date": "2019-05-13",
+ "abstract": "To describe the phenotype of individuals with intermediate allele (IA) CAG repeat length in the huntingtin (HTT) gene evaluated at the Parkinson's Disease Center and Movement Disorders Clinic (PDCMDC) at Baylor College of Medicine (BCM).",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31103960"
},
{
- "id": "omim:614153",
- "manubot_success": false,
- "link": "https://omim.org/entry/614153",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/614153. Skipping"
+ "id": "pmid:30961637",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30961637",
+ "title": "Modulation of mTOR and CREB pathways following mGluR5 blockade contribute to improved Huntington's pathology in zQ175 mice.",
+ "type": "article-journal",
+ "doi": "10.1186/s13041-019-0456-1",
+ "authors": [
+ ["Khaled S", "Abd-Elrahman"],
+ ["Stephen S G", "Ferguson"]
+ ],
+ "publisher": "Molecular brain",
+ "issn": "1756-6606",
+ "date": "2019-04-08",
+ "abstract": "Huntington's disease (HD) is a neurodegenerative disorder caused by a genetic abnormality in the huntingtin gene that leads to a polyglutamine repeat expansion of the huntingtin protein. The cleaved polyglutamine expansion of mutant huntingtin (mHTT) protein can form aggregates strongly correlated with HD progression. We have previously shown that the inhibition of mGluR5 using CTEP, a selective negative allosteric mGluR5 modulator, can delay disease progression and reduce in mHTT aggregates in the zQ175 mouse model of HD. This was paralleled by enhanced catalytic activity of Unc-51-like kinase 1 (ULK1), a kinase modulated by mammalian target of rapamycin (mTOR) and key regulator of autophagy initiation. In the present study, we show that CTEP can correct aberrant phosphoinositide 3-kinase (PI3K)/Akt/mTOR signaling detected in zQ175 mice that may underlie the enhanced ULK1 activity and activation of autophagy. We also show that CTEP can facilitate cAMP response element-binding protein (CREB)-mediated expression of brain-derived neurotrophic factor (BDNF) to foster neuronal survival and reduce apoptosis. Taken together, our findings provide the molecular evidence for how targeting mGluR5 using a well-tolerated selective NAM can mitigate two critical mechanisms of neurodegeneration, autophagy and apoptosis.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30961637"
},
{
- "id": "omim:603472",
- "manubot_success": false,
- "link": "https://omim.org/entry/603472",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/603472. Skipping"
+ "id": "pmid:30867264",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30867264",
+ "title": "Clinical manifestations of homozygote allele carriers in Huntington disease.",
+ "type": "article-journal",
+ "doi": "10.1212/wnl.0000000000007147",
+ "authors": [
+ ["Esther", "Cubo"],
+ ["Saul-Indra", "Martinez-Horta"],
+ ["Frederic Sampedro", "Santalo"],
+ ["Asunci\u00f3n Mart\u00ednez", "Descalls"],
+ ["Sara", "Calvo"],
+ ["Cecilia", "Gil-Polo"],
+ ["Ignacio", "Mu\u00f1oz"],
+ ["Katia", "Llano"],
+ ["Natividad", "Mariscal"],
+ ["Dolores", "Diaz"],
+ ["Aranzazu", "Gutierrez"],
+ ["Laura", "Aguado"],
+ ["Mar\u00eda A", "Ramos-Arroyo"]
+ ],
+ "publisher": "Neurology",
+ "issn": "1526-632X",
+ "date": "2019-03-13",
+ "abstract": "Because patients homozygous for Huntington disease (HD) receive the gain-of-function mutation in a double dose, one would expect a more toxic effect in homozygotes than in heterozygotes. Our aim was to investigate the phenotypic differences between homozygotes with both alleles \u226536 CAG repeats and heterozygotes with 1 allele \u226536 CAG repeats.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30867264"
},
{
- "id": "omim:618637",
- "manubot_success": false,
- "link": "https://omim.org/entry/618637",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/618637. Skipping"
+ "id": "pmid:30726572",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30726572",
+ "title": "Enhanced striatopallidal gamma-aminobutyric acid (GABA)",
+ "type": "article-journal",
+ "doi": "10.1002/mds.27622",
+ "authors": [
+ ["Tamara", "Perez-Rosello"],
+ ["Simon", "Gelman"],
+ ["Geoffrey", "Tombaugh"],
+ ["Roger", "Cachope"],
+ ["Vahri", "Beaumont"],
+ ["D James", "Surmeier"]
+ ],
+ "publisher": "Movement disorders : official journal of the Movement Disorder Society",
+ "issn": "1531-8257",
+ "date": "2019-02-06",
+ "abstract": "Huntington's disease (HD) is caused by a CAG repeat expansion in the huntingtin gene. This mutation leads to progressive dysfunction that is largely attributable to dysfunction of the striatum. The earliest signs of striatal pathology in HD are found in indirect pathway gamma-Aminobutyric acid (GABA)-ergic spiny projection neurons that innervate the external segment of the globus pallidus (GPe). What is less clear is whether the synaptic coupling of spiny projection neurons with GPe neurons changes in HD.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30726572"
},
{
- "id": "omim:601846",
- "manubot_success": false,
- "link": "https://omim.org/entry/601846",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/601846. Skipping"
+ "id": "pmid:30682531",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30682531",
+ "title": "Emerging differences between Huntington's disease-like 2 and Huntington's disease: A comparison using MRI brain volumetry.",
+ "type": "article-journal",
+ "doi": "10.1016/j.nicl.2019.101666",
+ "authors": [
+ ["David G", "Anderson"],
+ ["Mark", "Haagensen"],
+ ["Aline", "Ferreira-Correia"],
+ ["Ronald", "Pierson"],
+ ["Jonathan", "Carr"],
+ ["Amanda", "Krause"],
+ ["Russell L", "Margolis"]
+ ],
+ "publisher": "NeuroImage. Clinical",
+ "issn": "2213-1582",
+ "date": "2019-01-07",
+ "abstract": "Huntington's Disease-Like 2 (HDL2), caused by a CTG/CAG expansion in JPH3 on chromosome 16q24, is the most common Huntington's Disease (HD) phenocopy in populations with African ancestry. Qualitatively, brain MRIs of HDL2 patients have been indistinguishable from HD. To determine brain regions most affected in HDL2 a cross-sectional study using MRI brain volumetry was undertaken to compare the brains of nine HDL2, 11 HD and nine age matched control participants. Participants were ascertained from the region in South Africa with the world's highest HDL2 incidence. The HDL2 and HD patient groups showed no significant differences with respect to mean age at MRI, disease duration, abnormal triplet repeat length, or age at disease onset. Overall, intracerebral volumes were smaller in both affected groups compared to the control group. Comparing the HDL2 and HD groups across multiple covariates, cortical and subcortical volumes were similar with the exception that the HDL2 thalamic volumes were smaller. Consistent with other similarities between the two diseases, these results indicate a pattern of neurodegeneration in HDL2 that is remarkably similar to HD. However smaller thalamic volumes in HDL2 raises intriguing questions into the pathogenesis of both disorders, and how these volumetric differences relate to their respective phenotypes.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30682531"
},
{
- "id": "omim:258450",
- "manubot_success": false,
- "link": "https://omim.org/entry/258450",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/258450. Skipping"
+ "id": "pmid:30618191",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30618191",
+ "title": "Dynamic functional network connectivity in Huntington's disease and its associations with motor and cognitive measures.",
+ "type": "article-journal",
+ "doi": "10.1002/hbm.24504",
+ "authors": [
+ ["Flor A", "Espinoza"],
+ ["Jingyu", "Liu"],
+ ["Jennifer", "Ciarochi"],
+ ["Jessica A", "Turner"],
+ ["Victor M", "Vergara"],
+ ["Arvind", "Caprihan"],
+ ["Maria", "Misiura"],
+ ["Hans J", "Johnson"],
+ ["Jeffrey D", "Long"],
+ ["Jeremy H", "Bockholt"],
+ ["Jane S", "Paulsen"],
+ ["Vince D", "Calhoun"]
+ ],
+ "publisher": "Human brain mapping",
+ "issn": "1097-0193",
+ "date": "2019-01-07",
+ "abstract": "Dynamic functional network connectivity (dFNC) is an expansion of traditional, static FNC that measures connectivity variation among brain networks throughout scan duration. We used a large resting-state fMRI (rs-fMRI) sample from the PREDICT-HD study (N\u2009=\u2009183 Huntington disease gene mutation carriers [HDgmc] and N\u2009=\u200978 healthy control [HC] participants) to examine whole-brain dFNC and its associations with CAG repeat length as well as the product of scaled CAG length and age, a variable representing disease burden. We also tested for relationships between functional connectivity and motor and cognitive measurements. Group independent component analysis was applied to rs-fMRI data to obtain whole-brain resting state networks. FNC was defined as the correlation between RSN time-courses. Dynamic FNC behavior was captured using a sliding time window approach, and FNC results from each window were assigned to four clusters representing FNC states, using a k-means clustering algorithm. HDgmc individuals spent significantly more time in State-1 (the state with the weakest FNC pattern) compared to HC. However, overall HC individuals showed more FNC dynamism than HDgmc. Significant associations between FNC states and genetic and clinical variables were also identified. In FNC State-4 (the one that most resembled static FNC), HDgmc exhibited significantly decreased connectivity between the putamen and medial prefrontal cortex compared to HC, and this was significantly associated with cognitive performance. In FNC State-1, disease burden in HDgmc participants was significantly associated with connectivity between the postcentral gyrus and posterior cingulate cortex, as well as between the inferior occipital gyrus and posterior parietal cortex.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30618191"
},
{
- "id": "omim:157640",
- "manubot_success": false,
- "link": "https://omim.org/entry/157640",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/157640. Skipping"
+ "id": "pmid:30550751",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30550751",
+ "title": "Drp1/Fis1-mediated mitochondrial fragmentation leads to lysosomal dysfunction in cardiac models of Huntington's disease.",
+ "type": "article-journal",
+ "doi": "10.1016/j.yjmcc.2018.12.004",
+ "authors": [
+ ["A U", "Joshi"],
+ ["A E", "Ebert"],
+ ["B", "Haileselassie"],
+ ["D", "Mochly-Rosen"]
+ ],
+ "publisher": "Journal of molecular and cellular cardiology",
+ "issn": "1095-8584",
+ "date": "2018-12-11",
+ "abstract": "Huntington's disease (HD) is a fatal hereditary neurodegenerative disorder, best known for its clinical triad of progressive motor impairment, cognitive deficits and psychiatric disturbances, is caused by CAG-repeat expansion in exon 1 of Huntingtin (HTT). However, in addition to the neurological disease, mutant HTT (mHTT), which is ubiquitously expressed in all tissues, impairs other organ systems. Not surprisingly, cardiovascular dysautonomia as well as the deterioration of circadian rhythms are among the earliest detectable pathophysiological changes in individuals with HD. Mitochondrial dysfunction in the brain and skeletal muscle in HD has been well documented, as the disease progresses. However, not much is known about mitochondrial abnormalities in the heart. In this study, we describe a role for Drp1/Fis1-mediated excessive mitochondrial fission and dysfunction, associated with lysosomal dysfunction in H9C2 expressing long polyglutamine repeat (Q73) and in human iPSC-derived cardiomyocytes transfected with Q77. Expression of long polyglutamine repeat led to reduced ATP production and mitochondrial fragmentation. We observed an increased accumulation of damaged mitochondria in the lysosome that was coupled with lysosomal dysfunction. Importantly, reducing Drp1/Fis1-mediated mitochondrial damage significantly improved mitochondrial function and cell survival. Finally, reducing Fis1-mediated Drp1 recruitment to the mitochondria, using the selective inhibitor of this interaction, P110, improved mitochondrial structure in the cardiac tissue of R6/2 mice. We suggest that drugs focusing on the central nervous system will not address mitochondrial function across all organs, and therefore will not be a sufficient strategy to treat or slow down HD disease progression.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30550751"
},
{
- "id": "omim:604326",
- "manubot_success": false,
- "link": "https://omim.org/entry/604326",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/604326. Skipping"
+ "id": "pmid:30354976",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30354976",
+ "title": "Integration of Computed Tomographic Angiography Spot Sign and Noncontrast Computed Tomographic Hypodensities to Predict Hematoma Expansion.",
+ "type": "article-journal",
+ "doi": "10.1161/strokeaha.118.022010",
+ "authors": [
+ ["Andrea", "Morotti"],
+ ["Gregoire", "Boulouis"],
+ ["Andreas", "Charidimou"],
+ ["Kristin", "Schwab"],
+ ["Christina", "Kourkoulis"],
+ ["Christopher D", "Anderson"],
+ ["M Edip", "Gurol"],
+ ["Anand", "Viswanathan"],
+ ["Javier M", "Romero"],
+ ["Steven M", "Greenberg"],
+ ["Jonathan", "Rosand"],
+ ["Joshua N", "Goldstein"]
+ ],
+ "publisher": "Stroke",
+ "issn": "1524-4628",
+ "date": "2018-09-01",
+ "abstract": "Background and Purpose- Noncontrast computed tomographic (CT) hypodensities represent an alternative to the CT angiography spot sign (SS) to predict intracerebral hemorrhage (ICH) expansion. However, previous studies suggested that these markers predicted hematoma expansion independently from each other. We investigated whether the integration of SS and hypodensity (HD) improved the stratification of ICH expansion risk. Methods- A single-center cohort of consecutive patients with ICH was retrospectively analyzed. Patients with available CT angiography, baseline, and follow-up noncontrast CT images available were included. Trained readers reviewed all the images for SS and HD presence, and the study population was classified into 4 groups: SS and HD negative (SS-HD-), SS positive only (SS+HD-), HD positive only (SS-HD+), and SS and HD positive (SS+HD+). ICH expansion was defined as hematoma growth >33% or >6 mL. The association between SS and HD presence and ICH expansion was investigated with multivariable logistic regression. Results- A total of 745 subjects qualified for the analysis (median age, 73 years; 54.1% men). The rates of ICH expansion were 9.3% in SS-HD-, 25.8% in SS+HD-, 27.4% in SS-HD+, and 55.6% in SS+HD+ patients ( P<0.001). After adjustment for potential confounders and keeping SS-HD- subjects as reference, the risk of ICH expansion was increased in SS+HD- and SS-HD+ patients (odds ratio, 2.93, P=0.002 and odds ratio, 3.02, P<0.001, respectively). SS+HD+ subjects had the highest risk of hematoma growth (odds ratio, 9.50; P<0.001). Conclusions- Integration of SS and HD improves the stratification of hematoma growth risk and may help the selection of patients with ICH for antiexpansion treatment in clinical trials.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30354976"
},
{
- "id": "omim:616488",
- "manubot_success": false,
- "link": "https://omim.org/entry/616488",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/616488. Skipping"
+ "id": "pmid:30256717",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30256717",
+ "title": "A patient-derived cellular model for Huntington's disease reveals phenotypes at clinically relevant CAG lengths.",
+ "type": "article-journal",
+ "doi": "10.1091/mbc.e18-09-0590",
+ "authors": [
+ ["Claudia Lin-Kar", "Hung"],
+ ["Tamara", "Maiuri"],
+ ["Laura Erin", "Bowie"],
+ ["Ryan", "Gotesman"],
+ ["Susie", "Son"],
+ ["Mina", "Falcone"],
+ ["James Victor", "Giordano"],
+ ["Tammy", "Gillis"],
+ ["Virginia", "Mattis"],
+ ["Trevor", "Lau"],
+ ["Vickie", "Kwan"],
+ ["Vanessa", "Wheeler"],
+ ["Jonathan", "Schertzer"],
+ ["Karun", "Singh"],
+ ["Ray", "Truant"]
+ ],
+ "publisher": "Molecular biology of the cell",
+ "issn": "1939-4586",
+ "date": "2018-09-26",
+ "abstract": "The huntingtin protein participates in several cellular processes that are disrupted when the polyglutamine tract is expanded beyond a threshold of 37 CAG DNA repeats in Huntington's disease (HD). Cellular biology approaches to understand these functional disruptions in HD have primarily focused on cell lines with synthetically long CAG length alleles that clinically represent outliers in this disease and a more severe form of HD that lacks age onset. Patient-derived fibroblasts are limited to a finite number of passages before succumbing to cellular senescence. We used human telomerase reverse transcriptase (hTERT) to immortalize fibroblasts taken from individuals of varying age, sex, disease onset, and CAG repeat length, which we have termed TruHD cells. TruHD cells display classic HD phenotypes of altered morphology, size and growth rate, increased sensitivity to oxidative stress, aberrant adenosine diphosphate/adenosine triphosphate (ADP/ATP) ratios, and hypophosphorylated huntingtin protein. We additionally observed dysregulated reactive oxygen species (ROS)-dependent huntingtin localization to nuclear speckles in HD cells. We report the generation and characterization of a human, clinically relevant cellular model for investigating disease mechanisms in HD at the single-cell level, which, unlike transformed cell lines, maintains functions critical for huntingtin transcriptional regulation and genomic integrity.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30256717"
},
{
- "id": "omim:601068",
- "manubot_success": false,
- "link": "https://omim.org/entry/601068",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/601068. Skipping"
+ "id": "pmid:30171891",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30171891",
+ "title": "Mutational analysis implicates the amyloid fibril as the toxic entity in Huntington's disease.",
+ "type": "article-journal",
+ "doi": "10.1016/j.nbd.2018.08.019",
+ "authors": [
+ ["Kenneth W", "Drombosky"],
+ ["Sascha", "Rode"],
+ ["Ravi", "Kodali"],
+ ["Tija C", "Jacob"],
+ ["Michael J", "Palladino"],
+ ["Ronald", "Wetzel"]
+ ],
+ "publisher": "Neurobiology of disease",
+ "issn": "1095-953X",
+ "date": "2018-08-30",
+ "abstract": "In Huntington disease (HD), an expanded polyglutamine (polyQ\u202f>\u202f37) sequence within huntingtin (htt) exon1 leads to enhanced disease risk. It has proved difficult, however, to determine whether the toxic form generated by polyQ expansion is a misfolded or avid-binding monomer, an \u03b1-helix-rich oligomer, or a \u03b2-sheet-rich amyloid fibril. Here we describe an engineered htt exon1 analog featuring a short polyQ sequence that nonetheless quickly forms amyloid fibrils and causes HD-like toxicity in rat neurons and Drosophila. Additional modifications within the polyQ segment produce htt exon1 analogs that populate only spherical oligomers and are non-toxic in cells and flies. Furthermore, in mixture with expanded-polyQ htt exon1, the latter analogs in vitro suppress amyloid formation and promote oligomer formation, and in vivo rescue neurons and flies expressing mhtt exon1 from dysfunction and death. Thus, in our experiments, while htt exon1 toxicity tracks with aggregation propensity, it does so in spite of the toxic construct's possessing polyQ tracts well below those normally considered to be disease-associated. That is, aggregation propensity proves to be a more accurate surrogate for toxicity than is polyQ repeat length itself, strongly supporting a major toxic role for htt exon1 aggregation in HD. In addition, the results suggest that the aggregates that are most toxic in these model systems are amyloid-related. These engineered analogs are novel tools for mapping properties of polyQ self-assembly intermediates and products that should similarly be useful in the analysis of other expanded polyQ diseases. Small molecules with similar amyloid inhibitory properties might be developed into effective therapeutic agents.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30171891"
},
{
- "id": "omim:300123",
- "manubot_success": false,
- "link": "https://omim.org/entry/300123",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/300123. Skipping"
+ "id": "pmid:30138645",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30138645",
+ "title": "Genetic association analyses and meta-analysis of Dynorphin-Kappa Opioid system potential functional variants with heroin dependence.",
+ "type": "article-journal",
+ "doi": "10.1016/j.neulet.2018.08.023",
+ "authors": [
+ ["Ji", "Yuanyuan"],
+ ["Su", "Rui"],
+ ["Tang", "Hua"],
+ ["Cui", "Jingjing"],
+ ["Deji", "Cuola"],
+ ["Shi", "Yuhui"],
+ ["Wei", "Shuguang"]
+ ],
+ "publisher": "Neuroscience letters",
+ "issn": "1872-7972",
+ "date": "2018-08-20",
+ "abstract": "Prodynorphin (PDYN) binds to k-opioid receptors (KOPr; encoded by OPRK1) and is known to regulate dopaminergic tone, making this system important for drugs addiction. Dynorphin (Dyn)/KORr system are powerful effectors of stress-induced alterations in reward processing and dysphoric states. Thus, We identified 11 potential functional SNPs and one variable number of tandem repeat (VNTR) in this system, performed a case-control association analysis, investigated particular disease phenotypes, assessed the joint effect of variants in two genes, carried out a meta-analysis to analyze the association between this VNTR and Heroin dependence (HD) risk. Eleven single-nucleotide polymorphisms (SNPs) were genotyped using SNaPshot SNP technology. Participants included 566 healthy controls and 541 patients with HD. We found that PDYN polymorphisms modulate the susceptibility to HD. An increased risk of HD was significantly associated with H alleles of PDYN VNTR (\u03c7",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30138645"
},
{
- "id": "omim:607136",
- "manubot_success": false,
- "link": "https://omim.org/entry/607136",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/607136. Skipping"
+ "id": "pmid:30103338",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30103338",
+ "title": "Reduced Cancer Incidence in Huntington's Disease: Analysis in the Registry Study.",
+ "type": "article-journal",
+ "doi": "10.3233/jhd-170263",
+ "authors": [
+ ["Paul", "McNulty"],
+ ["Richard", "Pilcher"],
+ ["Raviram", "Ramesh"],
+ ["Renata", "Necuiniate"],
+ ["Alis", "Hughes"],
+ ["Daniel", "Farewell"],
+ ["Peter", "Holmans"],
+ ["Lesley", "Jones"]
+ ],
+ "publisher": "Journal of Huntington's disease",
+ "issn": "1879-6400",
+ "date": "2018-01-01",
+ "abstract": "People with Huntington's disease (HD) have been observed to have lower rates of cancers.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30103338"
},
{
- "id": "omim:187500",
- "manubot_success": false,
- "link": "https://omim.org/entry/187500",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/187500. Skipping"
+ "id": "pmid:30007561",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30007561",
+ "title": "AAV5-miHTT Gene Therapy Demonstrates Broad Distribution and Strong Human Mutant Huntingtin Lowering in a Huntington's Disease Minipig Model.",
+ "type": "article-journal",
+ "doi": "10.1016/j.ymthe.2018.06.021",
+ "authors": [
+ ["Melvin M", "Evers"],
+ ["Jana", "Miniarikova"],
+ ["Stefan", "Juhas"],
+ ["Astrid", "Vall\u00e8s"],
+ ["Bozena", "Bohuslavova"],
+ ["Jana", "Juhasova"],
+ ["Helena Kupcova", "Skalnikova"],
+ ["Petr", "Vodicka"],
+ ["Ivona", "Valekova"],
+ ["Cynthia", "Brouwers"],
+ ["Bas", "Blits"],
+ ["Jacek", "Lubelski"],
+ ["Hana", "Kovarova"],
+ ["Zdenka", "Ellederova"],
+ ["Sander J", "van Deventer"],
+ ["Harald", "Petry"],
+ ["Jan", "Motlik"],
+ ["Pavlina", "Konstantinova"]
+ ],
+ "publisher": "Molecular therapy : the journal of the American Society of Gene Therapy",
+ "issn": "1525-0024",
+ "date": "2018-06-25",
+ "abstract": "Huntington's disease (HD) is a fatal neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin gene. Previously, we showed strong huntingtin reduction and prevention of neuronal dysfunction in HD rodents using an engineered microRNA targeting human huntingtin, delivered via adeno-associated virus (AAV) serotype 5 vector with a transgene encoding an engineered miRNA against HTT mRNA (AAV5-miHTT). One of the challenges of rodents as a model of neurodegenerative diseases is their relatively small brain, making successful translation to the HD patient difficult. This is particularly relevant for gene therapy approaches, where distribution achieved upon local administration into the parenchyma is likely dependent on brain size and structure. Here, we aimed to demonstrate the translation of huntingtin-lowering gene therapy to a large-animal brain. We investigated the feasibility, efficacy, and tolerability of one-time intracranial administration of AAV5-miHTT in the transgenic HD (tgHD) minipig model. We detected widespread dose-dependent distribution of AAV5-miHTT throughout the tgHD minipig brain that correlated with the engineered microRNA expression. Both human mutant huntingtin mRNA and protein were significantly reduced in all brain regions transduced by AAV5-miHTT. The combination of widespread vector distribution and extensive huntingtin lowering observed with AAV5-miHTT supports the translation of a huntingtin-lowering gene therapy for HD from preclinical studies into the clinic.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30007561"
},
{
- "id": "omim:613267",
- "manubot_success": false,
- "link": "https://omim.org/entry/613267",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/613267. Skipping"
+ "id": "pmid:29902468",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/29902468",
+ "title": "Intravenous immunoglobulin ameliorates motor and cognitive deficits and neuropathology in R6/2 mouse model of Huntington's disease by decreasing mutant huntingtin protein level and normalizing NF-\u03baB signaling pathway.",
+ "type": "article-journal",
+ "doi": "10.1016/j.brainres.2018.06.009",
+ "authors": [
+ ["Shu-Ying", "Liu"],
+ ["Xiao-Lin", "Yu"],
+ ["Jie", "Zhu"],
+ ["Xiang-Meng", "Liu"],
+ ["Yue", "Zhang"],
+ ["Quan-Xiu", "Dong"],
+ ["Shan", "Ma"],
+ ["Rui-Tian", "Liu"]
+ ],
+ "publisher": "Brain research",
+ "issn": "1872-6240",
+ "date": "2018-06-11",
+ "abstract": "Huntington's disease (HD) is a fatal neurodegenerative disorder characterized by progressive movement disorders and cognitive deficits, which is caused by a CAG-repeat expansion encoding an extended polyglutamine (polyQ) tract in the huntingtin protein (HTT). Reduction of mutant HTT levels and inhibition of neuroinflammation has been proposed as a major therapeutic strategy in treating HD. Intravenous immunoglobulin (IVIg) therapy has been firmly established for the treatment of several autoimmune or inflammatory neurological diseases, either as adjunctive treatment or as first-line therapy. However, whether IVIg has therapeutic potential on HD remains unclear. Here we for the first time demonstrated that IVIg treatment remarkably rescued motor and cognitive deficits, prevented synaptic degeneration, attenuated neuroinflammation and oxidative stress in R6/2 mouse model. Further investigation showed that the beneficial effects of IVIg resulted from the reduced levels of mutant HTT and inhibition of NF-\u03baB signalling pathway. These findings suggest that IVIg is a promising therapeutic potential for HD.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29902468"
},
{
- "id": "omim:619216",
- "manubot_success": false,
- "link": "https://omim.org/entry/619216",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/619216. Skipping"
+ "id": "pmid:29813067",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/29813067",
+ "title": "Spontaneous gain of susceptibility suggests a novel mechanism of resistance to hybrid dysgenesis in Drosophila virilis.",
+ "type": "article-journal",
+ "doi": "10.1371/journal.pgen.1007400",
+ "authors": [
+ ["Sergei Y", "Funikov"],
+ ["Dina A", "Kulikova"],
+ ["George S", "Krasnov"],
+ ["Alexander P", "Rezvykh"],
+ ["Lubov N", "Chuvakova"],
+ ["Natalia G", "Shostak"],
+ ["Elena S", "Zelentsova"],
+ ["Justin P", "Blumenstiel"],
+ ["Michael B", "Evgen'ev"]
+ ],
+ "publisher": "PLoS genetics",
+ "issn": "1553-7404",
+ "date": "2018-05-29",
+ "abstract": "Syndromes of hybrid dysgenesis (HD) have been critical for our understanding of the transgenerational maintenance of genome stability by piRNA. HD in D. virilis represents a special case of HD since it includes simultaneous mobilization of a set of TEs that belong to different classes. The standard explanation for HD is that eggs of the responder strains lack an abundant pool of piRNAs corresponding to the asymmetric TE families transmitted solely by sperm. However, there are several strains of D. virilis that lack asymmetric TEs, but exhibit a \"neutral\" cytotype that confers resistance to HD. To characterize the mechanism of resistance to HD, we performed a comparative analysis of the landscape of ovarian small RNAs in strains that vary in their resistance to HD mediated sterility. We demonstrate that resistance to HD cannot be solely explained by a maternal piRNA pool that matches the assemblage of TEs that likely cause HD. In support of this, we have witnessed a cytotype shift from neutral (N) to susceptible (M) in a strain devoid of all major TEs implicated in HD. This shift occurred in the absence of significant change in TE copy number and expression of piRNAs homologous to asymmetric TEs. Instead, this shift is associated with a change in the chromatin profile of repeat sequences unlikely to be causative of paternal induction. Overall, our data suggest that resistance to TE-mediated sterility during HD may be achieved by mechanisms that are distinct from the canonical syndromes of HD.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29813067"
},
{
- "id": "omim:600223",
- "manubot_success": false,
- "link": "https://omim.org/entry/600223",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/600223. Skipping"
+ "id": "pmid:29685790",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/29685790",
+ "title": "Effect of Trinucleotide Repeats in the Huntington's Gene on Intelligence.",
+ "type": "article-journal",
+ "doi": "10.1016/j.ebiom.2018.03.031",
+ "authors": [
+ ["Jessica K", "Lee"],
+ ["Amy", "Conrad"],
+ ["Eric", "Epping"],
+ ["Kathy", "Mathews"],
+ ["Vincent", "Magnotta"],
+ ["Jeffrey D", "Dawson"],
+ ["Peg", "Nopoulos"]
+ ],
+ "publisher": "EBioMedicine",
+ "issn": "2352-3964",
+ "date": "2018-03-30",
+ "abstract": "Huntington's Disease (HD) is caused by an abnormality in the HTT gene. This gene includes trinucleotide repeats ranging from 10 to 35, and when expanded beyond 39, causes HD. We previously reported that CAG repeats in the normal range had a direct and beneficial effect on brain development with higher repeats being associated with higher cognitive function. The current study now expands this line of inquiry to evaluate the effects of CAG repeat throughout the entire spectrum of repeats from 15 to 58.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29685790"
},
{
- "id": "omim:314390",
- "manubot_success": false,
- "link": "https://omim.org/entry/314390",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/314390. Skipping"
+ "id": "pmid:29670796",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/29670796",
+ "title": "Huntington's Disease in a Patient Misdiagnosed as Conversion Disorder.",
+ "type": "article-journal",
+ "doi": "10.1155/2018/3915657",
+ "authors": [
+ ["Jo\u00e3o Machado", "Nogueira"],
+ ["Ana Margarida", "Franco"],
+ ["Susana", "Mendes"],
+ ["Anabela", "Valadas"],
+ ["Cristina", "Semedo"],
+ ["Gustavo", "Jesus"]
+ ],
+ "publisher": "Case reports in psychiatry",
+ "issn": "2090-682X",
+ "date": "2018-02-18",
+ "abstract": "Huntington's disease (HD) is an inherited, progressive, and neurodegenerative neuropsychiatric disorder caused by the expansion of cytosine-adenine-guanine (CAG) trinucleotide in Interested Transcript (IT) 15 gene on chromosome 4. This pathology typically presents in individuals aged between 30 and 50 years and the age of onset is inversely correlated with the length of the CAG repeat expansion. It is characterized by chorea, cognitive deficits, and psychiatric symptoms. Usually the psychiatric disorders precede motor and cognitive impairment, Major Depressive Disorder and anxiety disorders being the most common presentations. We present a clinical case of a 65-year-old woman admitted to our Psychiatric Acute Unit. During the 6 years preceding the admission, the patient had clinical assessments made several times by different specialties that focused only on isolated symptoms, disregarding the syndrome as a whole. In the course of her last admission, the patient was referred to our Neuropsychiatric Team, which made the provisional diagnosis of late-onset Huntington's disease, later confirmed by genetic testing. This clinical vignette highlights the importance of a multidisciplinary approach to atypical clinical presentations and raises awareness for the relevance of investigating carefully motor symptoms in psychiatric patients.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29670796"
},
{
- "id": "omim:616181",
- "manubot_success": false,
- "link": "https://omim.org/entry/616181",
- "note": "WARNING: Manubot does not support url:https://omim.org/entry/616181. Skipping"
+ "id": "pmid:29535594",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/29535594",
+ "title": "Precise Excision of the CAG Tract from the Huntingtin Gene by Cas9 Nickases.",
+ "type": "article-journal",
+ "doi": "10.3389/fnins.2018.00075",
+ "authors": [
+ ["Magdalena", "Dabrowska"],
+ ["Wojciech", "Juzwa"],
+ ["Wlodzimierz J", "Krzyzosiak"],
+ ["Marta", "Olejniczak"]
+ ],
+ "publisher": "Frontiers in neuroscience",
+ "issn": "1662-4548",
+ "date": "2018-02-26",
+ "abstract": "Huntington's disease (HD) is a progressive autosomal dominant neurodegenerative disorder caused by the expansion of CAG repeats in the first exon of the huntingtin gene (",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29535594"
},
{
- "id": "malacard:KNS007",
- "manubot_success": false,
- "link": "https://www.malacards.org/card/KNS007",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'url:https://www.malacards.org/card/KNS007']' timed out after 3 seconds"
+ "id": "pmid:29494703",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/29494703",
+ "title": "Premanifest Huntington's disease: Examination of oculomotor abnormalities in clinical practice.",
+ "type": "article-journal",
+ "doi": "10.1371/journal.pone.0193866",
+ "authors": [
+ ["Jessica Y", "Winder"],
+ ["Raymund A C", "Roos"]
+ ],
+ "publisher": "PloS one",
+ "issn": "1932-6203",
+ "date": "2018-03-01",
+ "abstract": "Different oculomotor abnormalities have been reported to occur in premanifest Huntington's disease. The aim of this study is to investigate which oculomotor items of the Unified Huntington's Disease Rating Scale (UHDRS) are affected in premanifest individuals compared to healthy controls, and if CAG repeat length and age are correlated with oculomotor abnormalities in premanifest Huntington's disease gene carriers.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29494703"
},
{
- "id": "doi:10.17161/2tmg0f25",
- "manubot_success": false,
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'doi:10.17161/2tmg0f25']' timed out after 3 seconds"
+ "id": "pmid:29480204",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/29480204",
+ "title": "Early Neurodegeneration in R6/2 Mice Carrying the Huntington's Disease Mutation with a Super-Expanded CAG Repeat, Despite Normal Lifespan.",
+ "type": "article-journal",
+ "doi": "10.3233/jhd-170265",
+ "authors": [
+ ["Catherine", "Kielar"],
+ ["A Jennifer", "Morton"]
+ ],
+ "publisher": "Journal of Huntington's disease",
+ "issn": "1879-6400",
+ "date": "2018-01-01",
+ "abstract": "The threshold of CAG repeat expansion in the HTT gene that causes HD is 36 CAG repeats, although 'superlong' expansions are found in individual neurons in postmortem brains. Previously, we showed that, compared to mice with <250 CAG repeats, onset of disease in R6/2 mice carrying superlong (>440) CAG repeat expansions was delayed, and disease progression was slower. Inclusion pathology also differed from 250 CAG repeat mice, being dominated by a novel kind of extranuclear neuronal inclusion (nENNI) that resembles a class of aggregate seen in patients with the adult onset form of HD. Here, we characterised neuropathology in R6/2 mice with >400 CAG repeats using light and electron microscopy. nENNIs were found with increased frequency and wider distribution with age. Some nENNIs appear to 'mature' as the disease develops, developing a multi-layered cored structure. Mice with superlong CAG repeats do not develop clinical signs until they are around 30-40 weeks of age, and they attain a normal life span (>2 years). Nevertheless, they show brain atrophy and unequivocal neuron loss from the striatum and cortex by 22 weeks of age, an age at which similar pathology is seen in 250 CAG repeat mice. Since this time-point is 'end stage' for a 250 CAG mouse, but very far (at least 18 months) from end stage for a\u200a> \u200a440 CAG repeat mouse, our data confirm that the appearance of clinical signs, the formation of inclusions, and neurodegeneration are processes that progress independently. A better understanding of the relationship between CAG repeat length, neurodegenerative pathways, and clinical behavioural signs is essential, if we are to find strategies to delay or reverse the course of this disease.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29480204"
},
{
- "id": "doi:10.1212/NXG.0000000000200245",
- "manubot_success": false,
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'doi:10.1212/NXG.0000000000200245']' timed out after 3 seconds"
+ "id": "pmid:29462355",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/29462355",
+ "title": "Small molecule modulator of protein disulfide isomerase attenuates mutant huntingtin toxicity and inhibits endoplasmic reticulum stress in a mouse model of Huntington's disease.",
+ "type": "article-journal",
+ "doi": "10.1093/hmg/ddy061",
+ "authors": [
+ ["Xiao", "Zhou"],
+ ["Gang", "Li"],
+ ["Anna", "Kaplan"],
+ ["Michael M", "Gaschler"],
+ ["Xiaoyan", "Zhang"],
+ ["Zhipeng", "Hou"],
+ ["Mali", "Jiang"],
+ ["Roseann", "Zott"],
+ ["Serge", "Cremers"],
+ ["Brent R", "Stockwell"],
+ ["Wenzhen", "Duan"]
+ ],
+ "publisher": "Human molecular genetics",
+ "issn": "1460-2083",
+ "date": "2018-05-01",
+ "abstract": "Huntington's disease (HD) is caused by a cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the huntingtin (HTT) gene encoding an elongated polyglutamine tract within the N-terminal of the huntingtin protein (Htt) and leads to Htt misfolding, aberrant protein aggregation, and progressive appearance of disease symptoms. Chronic activation of endoplasmic reticulum (ER) stress by mutant Htt (mHtt) results in cellular dysfunction and ultimately cell death. Protein disulfide isomerase (PDI) is a chaperone protein located in the ER. Our previous studies demonstrated that mHtt caused PDI to accumulate at mitochondria-associated ER membranes and triggered cell death, and that modulating PDI activity using small molecules protected cells again mHtt toxicity in cell and brain slice models of HD. In this study, we demonstrated that PDI is upregulated in the HD human brain, in cell and mouse models. Chronic administration of a reversible, brain penetrable small molecule PDI modulator, LOC14 (20 mg/kg/day), significantly improved motor function, attenuated brain atrophy and extended survival in the N171-82Q HD mice. Moreover, LOC14 preserved medium spiny neuronal marker dopamine- and cyclic-AMP-regulated phosphoprotein of molecular weight 32\u00a0000 (DARPP32) levels in the striatum of HD mice. Mechanistic study revealed that LOC14 suppressed mHtt-induced ER stress, indicated by repressing the abnormally upregulated ER stress proteins in HD models. These findings suggest that LOC14 is promising to be further optimized for clinical trials of HD, and modulation of signaling pathways coping with ER stress may constitute an attractive approach to reduce mHtt toxicity and identify new therapeutic targets for treatment of HD.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29462355"
},
{
- "id": "doi:10.1016/j.omsc.2023.100340",
+ "id": "pmid:29378824",
"manubot_success": true,
- "title": "Treatment of the median mandibular cleft in Richieri-Costa-Pereira syndrome with a customized total mandibular prosthesis: A case report",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/29378824",
+ "title": "Chromosomal instability during neurogenesis in Huntington's disease.",
"type": "article-journal",
- "doi": "10.1016/j.omsc.2023.100340",
+ "doi": "10.1242/dev.156844",
"authors": [
- ["Ryuichi", "Hoshi"],
- ["Paula", "Marcella Silva Drago"],
- ["Henrique", "Mascarenhas Villela"],
- ["Gabriela", "Gayer Sheibler"],
- ["Daniel", "Serra Cassano"],
- ["Fernanda", "Barros Silva de Pedreira Barbosa"],
- ["Lissa", "Hoshi"],
- ["Isadora", "dos Santos Lima"]
+ ["Albert", "Ruzo"],
+ ["Gist F", "Croft"],
+ ["Jakob J", "Metzger"],
+ ["Szilvia", "Galgoczi"],
+ ["Lauren J", "Gerber"],
+ ["Cecilia", "Pellegrini"],
+ ["Hanbin", "Wang"],
+ ["Maria", "Fenner"],
+ ["Stephanie", "Tse"],
+ ["Adam", "Marks"],
+ ["Corbyn", "Nchako"],
+ ["Ali H", "Brivanlou"]
],
- "publisher": "Oral and Maxillofacial Surgery Cases",
- "issn": "",
- "date": "2024-03-01",
- "link": "https://doi.org/g8rxvs",
- "abstract": "",
+ "publisher": "Development (Cambridge, England)",
+ "issn": "1477-9129",
+ "date": "2018-01-29",
+ "abstract": "Huntington's disease (HD) is a fatal neurodegenerative disease caused by expansion of CAG repeats in the Huntingtin gene (",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: doi:10.1016/j.omsc.2023.100340"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29378824"
},
{
- "id": "genereviews:NBK1333",
- "manubot_success": false,
- "link": "https://www.ncbi.nlm.nih.gov/books/NBK1333",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'url:https://www.ncbi.nlm.nih.gov/books/NBK1333']' timed out after 3 seconds"
+ "id": "pmid:29367444",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/29367444",
+ "title": "Neurofilament light protein in blood predicts regional atrophy in Huntington disease.",
+ "type": "article-journal",
+ "doi": "10.1212/wnl.0000000000005005",
+ "authors": [
+ ["Eileanoir B", "Johnson"],
+ ["Lauren M", "Byrne"],
+ ["Sarah", "Gregory"],
+ ["Filipe B", "Rodrigues"],
+ ["Kaj", "Blennow"],
+ ["Alexandra", "Durr"],
+ ["Blair R", "Leavitt"],
+ ["Raymund A", "Roos"],
+ ["Henrik", "Zetterberg"],
+ ["Sarah J", "Tabrizi"],
+ ["Rachael I", "Scahill"],
+ ["Edward J", "Wild"]
+ ],
+ "publisher": "Neurology",
+ "issn": "1526-632X",
+ "date": "2018-01-24",
+ "abstract": "Neurofilament light (NfL) protein in blood plasma has been proposed as a prognostic biomarker of neurodegeneration in a number of conditions, including Huntington disease (HD). This study investigates the regional distribution of NfL-associated neural pathology in HD gene expansion carriers.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29367444"
},
{
- "id": "genereviews:NBK1491",
- "manubot_success": false,
- "link": "https://www.ncbi.nlm.nih.gov/books/NBK1491",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'url:https://www.ncbi.nlm.nih.gov/books/NBK1491']' timed out after 3 seconds"
+ "id": "pmid:29253686",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/29253686",
+ "title": "Suicidal ideation and suicidal behavior according to the C-SSRS in a European cohort of Huntington's disease gene expansion carriers.",
+ "type": "article-journal",
+ "doi": "10.1016/j.jad.2017.11.074",
+ "authors": [
+ ["Erik", "van Duijn"],
+ ["Eslie M", "Vrijmoeth"],
+ ["Erik J", "Giltay"],
+ ["G", "Bernhard Landwehrmeyer"]
+ ],
+ "publisher": "Journal of affective disorders",
+ "issn": "1573-2517",
+ "date": "2017-11-15",
+ "abstract": "Huntington's disease (HD) gene expansion carriers are at an increased risk of suicide, but so far, no studies have investigated the full spectrum of suicidality, including suicidal ideation, suicidal behavior and self-injurious behavior.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29253686"
},
{
- "id": "genereviews:NBK1184",
- "manubot_success": false,
- "link": "https://www.ncbi.nlm.nih.gov/books/NBK1184",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'url:https://www.ncbi.nlm.nih.gov/books/NBK1184']' timed out after 3 seconds"
+ "id": "pmid:29229845",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/29229845",
+ "title": "Brain urea increase is an early Huntington's disease pathogenic event observed in a prodromal transgenic sheep model and HD cases.",
+ "type": "article-journal",
+ "doi": "10.1073/pnas.1711243115",
+ "authors": [
+ ["Renee R", "Handley"],
+ ["Suzanne J", "Reid"],
+ ["Rudiger", "Brauning"],
+ ["Paul", "Maclean"],
+ ["Emily R", "Mears"],
+ ["Imche", "Fourie"],
+ ["Stefano", "Patassini"],
+ ["Garth J S", "Cooper"],
+ ["Skye R", "Rudiger"],
+ ["Clive J", "McLaughlan"],
+ ["Paul J", "Verma"],
+ ["James F", "Gusella"],
+ ["Marcy E", "MacDonald"],
+ ["Henry J", "Waldvogel"],
+ ["C Simon", "Bawden"],
+ ["Richard L M", "Faull"],
+ ["Russell G", "Snell"]
+ ],
+ "publisher": "Proceedings of the National Academy of Sciences of the United States of America",
+ "issn": "1091-6490",
+ "date": "2017-12-11",
+ "abstract": "The neurodegenerative disorder Huntington's disease (HD) is typically characterized by extensive loss of striatal neurons and the midlife onset of debilitating and progressive chorea, dementia, and psychological disturbance. HD is caused by a CAG repeat expansion in the",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29229845"
},
{
- "id": "genereviews:NBK1196",
- "manubot_success": false,
- "link": "https://www.ncbi.nlm.nih.gov/books/NBK1196",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'url:https://www.ncbi.nlm.nih.gov/books/NBK1196']' timed out after 3 seconds"
+ "id": "pmid:29043641",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/29043641",
+ "title": "Measuring Dynamic Behavior of Trinucleotide Repeat Tracts In Vivo in Saccharomyces cerevisiae.",
+ "type": "article-journal",
+ "doi": "10.1007/978-1-4939-7306-4_30",
+ "authors": [
+ ["Gregory M", "Williams"],
+ ["Jennifer A", "Surtees"]
+ ],
+ "publisher": "Methods in molecular biology (Clifton, N.J.)",
+ "issn": "1940-6029",
+ "date": "2018-01-01",
+ "abstract": "Trinucleotide repeat (TNR) tracts are inherently unstable during DNA replication, leading to repeat expansions and/or contractions. Expanded tracts are the cause of over 40 neurodegenerative and neuromuscular diseases. In this chapter, we focus on the (CNG)",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29043641"
},
{
- "id": "genereviews:NBK1268",
- "manubot_success": false,
- "link": "https://www.ncbi.nlm.nih.gov/books/NBK1268",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'url:https://www.ncbi.nlm.nih.gov/books/NBK1268']' timed out after 3 seconds"
+ "id": "pmid:28986324",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/28986324",
+ "title": "The ubiquitin conjugating enzyme Ube2W regulates solubility of the Huntington's disease protein, huntingtin.",
+ "type": "article-journal",
+ "doi": "10.1016/j.nbd.2017.10.002",
+ "authors": [
+ ["Bo", "Wang"],
+ ["Li", "Zeng"],
+ ["Sean A", "Merillat"],
+ ["Svetlana", "Fischer"],
+ ["Joseph", "Ochaba"],
+ ["Leslie M", "Thompson"],
+ ["Sami J", "Barmada"],
+ ["Kenneth M", "Scaglione"],
+ ["Henry L", "Paulson"]
+ ],
+ "publisher": "Neurobiology of disease",
+ "issn": "1095-953X",
+ "date": "2017-10-03",
+ "abstract": "Huntington's disease (HD) is caused by a CAG repeat expansion that encodes a polyglutamine (polyQ) expansion in the HD disease protein, huntingtin (HTT). PolyQ expansion promotes misfolding and aggregation of mutant HTT (mHTT) within neurons. The cellular pathways, including ubiquitin-dependent processes, by which mHTT is regulated remain incompletely understood. Ube2W is the only ubiquitin conjugating enzyme (E2) known to ubiquitinate substrates at their amino (N)-termini, likely favoring substrates with disordered N-termini. By virtue of its N-terminal polyQ domain, HTT has an intrinsically disordered amino terminus. In studies employing immortalized cells, primary neurons and a knock-in (KI) mouse model of HD, we tested the effect of Ube2W deficiency on mHTT levels, aggregation and neurotoxicity. In cultured cells, deficiency of Ube2W activity markedly decreases mHTT aggregate formation and increases the level of soluble monomers, while reducing mHTT-induced cytotoxicity. Consistent with this result, the absence of Ube2W in HdhQ200 KI mice significantly increases levels of soluble monomeric mHTT while reducing insoluble oligomeric species. This study sheds light on the potential function of the non-canonical ubiquitin-conjugating enzyme, Ube2W, in this polyQ neurodegenerative disease.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28986324"
},
{
- "id": "genereviews:NBK268647",
- "manubot_success": false,
- "link": "https://www.ncbi.nlm.nih.gov/books/NBK268647",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'url:https://www.ncbi.nlm.nih.gov/books/NBK268647']' timed out after 3 seconds"
+ "id": "pmid:28729730",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/28729730",
+ "title": "A selective inhibitor of histone deacetylase 3 prevents cognitive deficits and suppresses striatal CAG repeat expansions in Huntington's disease mice.",
+ "type": "article-journal",
+ "doi": "10.1038/s41598-017-05125-2",
+ "authors": [
+ ["Nuria", "Suelves"],
+ ["Lucy", "Kirkham-McCarthy"],
+ ["Robert S", "Lahue"],
+ ["Silvia", "Gin\u00e9s"]
+ ],
+ "publisher": "Scientific reports",
+ "issn": "2045-2322",
+ "date": "2017-07-20",
+ "abstract": "Huntington's disease (HD) is a neurodegenerative disorder whose major symptoms include progressive motor and cognitive dysfunction. Cognitive decline is a critical quality of life concern for HD patients and families. The enzyme histone deacetylase 3 (HDAC3) appears to be important in HD pathology by negatively regulating genes involved in cognitive functions. Furthermore, HDAC3 has been implicated in the aberrant transcriptional patterns that help cause disease symptoms in HD mice. HDAC3 also helps fuel CAG repeat expansions in human cells, suggesting that HDAC3 may power striatal expansions in the HTT gene thought to drive disease progression. This multifaceted role suggests that early HDAC3 inhibition offers an attractive mechanism to prevent HD cognitive decline and to suppress striatal expansions. This hypothesis was investigated by treating Hdh",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28729730"
},
{
- "id": "genereviews:NBK1466",
- "manubot_success": false,
- "link": "https://www.ncbi.nlm.nih.gov/books/NBK1466",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'url:https://www.ncbi.nlm.nih.gov/books/NBK1466']' timed out after 3 seconds"
+ "id": "pmid:28698602",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/28698602",
+ "title": "Polyglutamine expansion affects huntingtin conformation in multiple Huntington's disease models.",
+ "type": "article-journal",
+ "doi": "10.1038/s41598-017-05336-7",
+ "authors": [
+ ["Manuel", "Daldin"],
+ ["Valentina", "Fodale"],
+ ["Cristina", "Cariulo"],
+ ["Lucia", "Azzollini"],
+ ["Margherita", "Verani"],
+ ["Paola", "Martufi"],
+ ["Maria Carolina", "Spiezia"],
+ ["Sean M", "Deguire"],
+ ["Marta", "Cherubini"],
+ ["Douglas", "Macdonald"],
+ ["Andreas", "Weiss"],
+ ["Alberto", "Bresciani"],
+ ["Jean-Paul Gerard", "Vonsattel"],
+ ["Lara", "Petricca"],
+ ["J Lawrence", "Marsh"],
+ ["Silvia", "Gines"],
+ ["Iolanda", "Santimone"],
+ ["Massimo", "Marano"],
+ ["Hilal A", "Lashuel"],
+ ["Ferdinando", "Squitieri"],
+ ["Andrea", "Caricasole"]
+ ],
+ "publisher": "Scientific reports",
+ "issn": "2045-2322",
+ "date": "2017-07-11",
+ "abstract": "Conformational changes in disease-associated or mutant proteins represent a key pathological aspect of Huntington's disease (HD) and other protein misfolding diseases. Using immunoassays and biophysical approaches, we and others have recently reported that polyglutamine expansion in purified or recombinantly expressed huntingtin (HTT) proteins affects their conformational properties in a manner dependent on both polyglutamine repeat length and temperature but independent of HTT protein fragment length. These findings are consistent with the HD mutation affecting structural aspects of the amino-terminal region of the protein, and support the concept that modulating mutant HTT conformation might provide novel therapeutic and diagnostic opportunities. We now report that the same conformational TR-FRET based immunoassay detects polyglutamine- and temperature-dependent changes on the endogenously expressed HTT protein in peripheral tissues and post-mortem HD brain tissue, as well as in tissues from HD animal models. We also find that these temperature- and polyglutamine-dependent conformational changes are sensitive to bona-fide phosphorylation on S13 and S16 within the N17 domain of HTT. These findings provide key clinical and preclinical relevance to the conformational immunoassay, and provide supportive evidence for its application in the development of therapeutics aimed at correcting the conformation of polyglutamine-expanded proteins as well as the pharmacodynamics readouts to monitor their efficacy in preclinical models and in HD patients.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28698602"
},
{
- "id": "genereviews:NBK1487",
+ "id": "pmid:28642124",
"manubot_success": true,
- "link": "http://www.ncbi.nlm.nih.gov/books/NBK1487/",
- "title": "COMP-Related Pseudoachondroplasia",
- "type": "chapter",
- "doi": "",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/28642124",
+ "title": "Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study.",
+ "type": "article-journal",
+ "doi": "10.1016/s1474-4422(17)30161-8",
"authors": [
- ["Michael D.", "Briggs"],
- ["Michael J.", "Wright"]
+ ["Davina J Hensman", "Moss"],
+ ["Antonio F", "Pardi\u00f1as"],
+ ["Douglas", "Langbehn"],
+ ["Kitty", "Lo"],
+ ["Blair R", "Leavitt"],
+ ["Raymund", "Roos"],
+ ["Alexandra", "Durr"],
+ ["Simon", "Mead"],
+ ["Peter", "Holmans"],
+ ["Lesley", "Jones"],
+ ["Sarah J", "Tabrizi"]
],
- "publisher": "GeneReviews\u00ae",
- "issn": "",
- "date": "1993-01-01",
- "abstract": "COMP-related pseudoachondroplasia (COMP-PSACH) is characterized by normal length at birth and normal facies. Often the presenting feature is a waddling gait, recognized at the onset of walking. Typically, the growth rate falls below the standard growth curve by approximately age two years, leading to a moderately severe form of disproportionate short-limb short stature. Joint pain during childhood, particularly in the large joints of the lower extremities, is common. Degenerative joint disease is progressive; approximately 50% of individuals with COMP-PSACH eventually require hip replacement surgery., The diagnosis of COMP-PSACH can be made on the basis of clinical findings and radiographic features. Identification of a heterozygous pathogenic variant in COMP on molecular genetic testing establishes the diagnosis if clinical features are inconclusive., Treatment of manifestations: Analgesics for joint pain; encourage physical activities that do not cause excessive wear and/or damage to the joints; osteotomy for lower limb malalignment; rarely, surgery for scoliosis; C1-C2 fixation for symptoms and radiographic evidence of cervical spine instability; attention to and social support for psychosocial issues related to short stature for affected individuals and their families. Surveillance: Assess growth at each visit throughout childhood. Regular examinations for evidence of symptomatic joint hypermobility and/or lower limb malalignment, kyphoscoliosis, degenerative joint disease, and neurologic manifestations, particularly spinal cord compression secondary to odontoid hypoplasia. Assess for psychosocial issues annually or at each visit. Agents/circumstances to avoid: In those with odontoid hypoplasia, extreme neck flexion and extension should be avoided., COMP-PSACH is inherited in an autosomal dominant manner. Some individuals diagnosed with COMP-PSACH have an affected parent. A proband diagnosed with COMP-PSACH may have the disorder as the result of a de novo pathogenic variant. Each child of an individual with COMP-PSACH and a reproductive partner with normal bone growth has a 50% chance of inheriting the COMP pathogenic variant and having COMP-PSACH. Because many individuals with short stature select reproductive partners with short stature, offspring of individuals with COMP-PSACH may be at risk of having double heterozygosity for two dominantly inherited bone growth disorders. Once the COMP pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.",
- "language": "eng",
- "note": "PMID: 20301660\nThis CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: url:https://www.ncbi.nlm.nih.gov/books/NBK1487"
+ "publisher": "The Lancet. Neurology",
+ "issn": "1474-4465",
+ "date": "2017-06-20",
+ "abstract": "Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28642124"
},
{
- "id": "genereviews:NBK541729",
+ "id": "pmid:28582868",
"manubot_success": true,
- "link": "http://www.ncbi.nlm.nih.gov/books/NBK541729/",
- "title": "Spinocerebellar Ataxia Type 37",
- "type": "chapter",
- "doi": "",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/28582868",
+ "title": "Dynamic Prediction of Motor Diagnosis in\u00a0Huntington's Disease Using a Joint Modeling Approach.",
+ "type": "article-journal",
+ "doi": "10.3233/jhd-170236",
"authors": [
- ["Antoni", "Matilla-Due\u00f1as"],
- ["Victor", "Volpini"]
+ ["Kan", "Li"],
+ ["Erin", "Furr-Stimming"],
+ ["Jane S", "Paulsen"],
+ ["Sheng", "Luo"]
],
- "publisher": "GeneReviews\u00ae",
- "issn": "",
- "date": "1993-01-01",
- "abstract": "Spinocerebellar ataxia type 37 (SCA37) is characterized by adult onset, dysarthria, slowly progressive gait and limb ataxia with severe dysmetria in the lower extremities, mild dysmetria in the upper extremities, dysphagia, and abnormal ocular movements (dysmetric vertical saccades, irregular and slow vertical smooth pursuit, slow vertical optokinetic nystagmus, and oscillopsia (visual disturbance in which objects appear to oscillate). In most individuals, the initial signs/symptoms include falls, dysarthria, or clumsiness followed by a complete cerebellar syndrome. A distinctive clinical feature is the presence of altered vertical eye movements in early stages of the disease, even preceding ataxia symptoms. Clinical progression is slow and affected individuals usually become wheelchair bound between ten and 33 years after disease onset., The diagnosis of SCA37 is established in a proband by identification of a heterozygous ATTTC repeat insertion within DAB1 by molecular genetic testing. All affected persons have 31-75 ATTTC repeats, flanked on both sides by polymorphic ATTTT repeats over 58 units., Treatment of manifestations: Currently, no treatment reverts the course of the disease. Speech therapy to improve communication and ameliorate dysphagia; thickness modification of food and fluids to prevent aspiration; physical therapy to train balance; use of external devices (e.g., canes or walkers) when needed to avoid falls; occupational/behavioral therapy. Surveillance: Scale for the Assessment and Rating of Ataxia (SARA) score annually; electrooculographic tests may be performed every two years (cooperation required); brain MRI volumetry every two years., SCA37 is inherited in an autosomal dominant manner. All individuals diagnosed to date with SCA37 have an affected parent. Each child of an individual with SCA37 is at a 50% risk of inheriting the intronic ATTTC repeat insertion within DAB1. Prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible if the ATTTC repeat insertion within DAB1 has been identified in an affected family member.",
- "language": "eng",
- "note": "PMID: 31145571\nThis CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: url:https://www.ncbi.nlm.nih.gov/books/NBK541729"
-},
-{
- "id": "genereviews:NBK1119",
- "manubot_success": false,
- "link": "https://www.ncbi.nlm.nih.gov/books/NBK1119",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'url:https://www.ncbi.nlm.nih.gov/books/NBK1119']' timed out after 3 seconds"
-},
-{
- "id": "genereviews:NBK1165",
- "manubot_success": false,
- "link": "https://www.ncbi.nlm.nih.gov/books/NBK1165",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'url:https://www.ncbi.nlm.nih.gov/books/NBK1165']' timed out after 3 seconds"
-},
-{
- "id": "genereviews:NBK599589",
- "manubot_success": false,
- "link": "https://www.ncbi.nlm.nih.gov/books/NBK599589",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'url:https://www.ncbi.nlm.nih.gov/books/NBK599589']' timed out after 3 seconds"
-},
-{
- "id": "genereviews:NBK1384",
- "manubot_success": false,
- "link": "https://www.ncbi.nlm.nih.gov/books/NBK1384",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'url:https://www.ncbi.nlm.nih.gov/books/NBK1384']' timed out after 3 seconds"
-},
-{
- "id": "genereviews:NBK1281",
- "manubot_success": false,
- "link": "https://www.ncbi.nlm.nih.gov/books/NBK1281",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'url:https://www.ncbi.nlm.nih.gov/books/NBK1281']' timed out after 3 seconds"
-},
-{
- "id": "genereviews:NBK1305",
- "manubot_success": false,
- "link": "https://www.ncbi.nlm.nih.gov/books/NBK1305",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'url:https://www.ncbi.nlm.nih.gov/books/NBK1305']' timed out after 3 seconds"
+ "publisher": "Journal of Huntington's disease",
+ "issn": "1879-6400",
+ "date": "2017-01-01",
+ "abstract": "Prediction of motor diagnosis in Huntington's disease (HD) can be improved by incorporating other phenotypic and biological clinical measures in addition to cytosine-adenine-guanine (CAG) repeat length and age.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28582868"
},
{
- "id": "genereviews:NBK1529",
+ "id": "pmid:28406926",
"manubot_success": true,
- "link": "http://www.ncbi.nlm.nih.gov/books/NBK1529/",
- "title": "Huntington Disease-Like 2",
- "type": "chapter",
- "doi": "",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/28406926",
+ "title": "High-resolution respirometry of fine-needle muscle biopsies in pre-manifest Huntington's disease expansion mutation carriers shows normal mitochondrial respiratory function.",
+ "type": "article-journal",
+ "doi": "10.1371/journal.pone.0175248",
"authors": [
- ["David G.", "Anderson"],
- ["Amanda", "Krause"],
- ["Russell L.", "Margolis"]
+ ["Eva", "Buck"],
+ ["Martina", "Z\u00fcgel"],
+ ["Uwe", "Schumann"],
+ ["Tamara", "Merz"],
+ ["Anja M", "Gumpp"],
+ ["Anke", "Witting"],
+ ["J\u00fcrgen M", "Steinacker"],
+ ["G Bernhard", "Landwehrmeyer"],
+ ["Patrick", "Weydt"],
+ ["Enrico", "Calzia"],
+ ["Katrin S", "Lindenberg"]
],
- "publisher": "GeneReviews\u00ae",
- "issn": "",
- "date": "1993-01-01",
- "abstract": "Huntington disease-like 2 (HDL2) typically presents in midlife with a relentless progressive triad of movement, emotional, and cognitive abnormalities that lead to death within ten to 20 years. HDL2 cannot be differentiated from Huntington disease (HD) clinically. Neurologic abnormalities include chorea, hypokinesia (rigidity, bradykinesia), dysarthria, abnormalities of eye movements and gait, and hyperreflexia in the later stages of the disease. There is a strong correlation between the duration of the disease and the progression of motor and cognitive signs and symptoms., The diagnosis of HDL2 is established in a proband with characteristic clinical findings and heterozygous expansion of 40 or more CTG trinucleotide repeats in JPH3 identified by molecular genetic testing., Treatment of manifestations: Treatment is symptomatic and is presumably similar to that for HD and other neurodegenerative disorders \u2013 although this must be considered speculative pending objective data. Pharmacologic agents that may suppress abnormal movements include tetrabenazine and its derivatives or low-dose neuroleptic agents such as fluphenazine and haloperidol. Remove loose rugs and clutter from the individual's home and minimize or eliminate the need for stairs to help prevent falls and other injuries; physical therapy evaluation and treatment for mobility issues; speech therapy, communication devices, and environmental modifications for dysarthria; speech-language pathology and nutrition referrals for dysphagia; food should be prepared in such a manner as to prevent choking; feeding changes when needed to minimize risk of aspiration; driving may need to be curtailed or limited to prevent risk of accidents; planning for financial matters; environmental interventions for cognitive issues; antidepressants, antipsychotics, mood stabilizers (lithium, valproic acid, carbamazepine, and lamotrigine), electroconvulsive therapy, and occasionally stimulants may improve psychiatric manifestations. Education about the course of disease; social work and care coordination support. Surveillance: Annual evaluation or more frequently as needed to assess motor skills including gait and abnormal movements; physical therapy assessment of mobility and appropriate strategies or devices to minimize falls; assess cognitive skills and driving safety to assure that affected individuals do not present a danger to themselves or others; assess weight, nutrition, swallowing, and risk of aspiration in order to implement feeding changes when necessary; assess for psychiatric manifestations, including mood, suicidality, anxiety, irritability, and apathy; assess sleep and sexual concerns; assess family needs; assess planning for future (financial, legal issues). Agents/circumstances to avoid: Any agents that increase ataxia should be used with caution; begin psychoactive medicines at lower doses and increase doses carefully; minimize polypharmacy, which may increase the risk of delirium., HDL2 is inherited in an autosomal dominant manner. Most individuals with HDL2 have an affected parent. At conception, each child of an individual with HDL2 has a 50% chance of inheriting the HDL2-causing allele. Offspring who inherit a pathogenic (full-penetrance) HDL2-causing allele (\u226540 CTG repeats) are considered at risk of developing HDL2 in their lifetime; offspring who inherit an allele of questionable significance (29-39 CTG repeats) may or may not develop manifestations of HDL2. Testing of asymptomatic adults at risk for HDL2 is possible once a heterozygous expansion of a CTG repeat in JPH3 has been identified in an affected family member. Testing for the JPH3 CTG repeat expansion in the absence of definite manifestations of the disease is predictive testing. Prudence suggests following the same genetic testing guidelines used for HD, including counseling prior to testing, a confidant to serve as a social support, and availability of counseling following the disclosure of genetic results. If the presence of an HDL2-causing allele has been confirmed in the affected parent or in an affected relative of the at-risk parent, prenatal and preimplantation genetic testing are possible.",
- "language": "eng",
- "note": "PMID: 20301701\nThis CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: url:https://www.ncbi.nlm.nih.gov/books/NBK1529"
+ "publisher": "PloS one",
+ "issn": "1932-6203",
+ "date": "2017-04-13",
+ "abstract": "Alterations in mitochondrial respiration are an important hallmark of Huntington's disease (HD), one of the most common monogenetic causes of neurodegeneration. The ubiquitous expression of the disease causing mutant huntingtin gene raises the prospect that mitochondrial respiratory deficits can be detected in skeletal muscle. While this tissue is readily accessible in humans, transgenic animal models offer the opportunity to cross-validate findings and allow for comparisons across organs, including the brain. The integrated respiratory chain function of the human vastus lateralis muscle was measured by high-resolution respirometry (HRR) in freshly taken fine-needle biopsies from seven pre-manifest HD expansion mutation carriers and nine controls. The respiratory parameters were unaffected. For comparison skeletal muscle isolated from HD knock-in mice (HdhQ111) as well as a broader spectrum of tissues including cortex, liver and heart muscle were examined by HRR. Significant changes of mitochondrial respiration in the HdhQ knock-in mouse model were restricted to the liver and the cortex. Mitochondrial mass as quantified by mitochondrial DNA copy number and citrate synthase activity was stable in murine HD-model tissue compared to control. mRNA levels of key enzymes were determined to characterize mitochondrial metabolic pathways in HdhQ mice. We demonstrated the feasibility to perform high-resolution respirometry measurements from small human HD muscle biopsies. Furthermore, we conclude that alterations in respiratory parameters of pre-manifest human muscle biopsies are rather limited and mirrored by a similar absence of marked alterations in HdhQ skeletal muscle. In contrast, the HdhQ111 murine cortex and liver did show respiratory alterations highlighting the tissue specific nature of mutant huntingtin effects on respiration.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28406926"
},
{
- "id": "genereviews:NBK153723",
+ "id": "pmid:28359739",
"manubot_success": true,
- "link": "http://www.ncbi.nlm.nih.gov/books/NBK153723/",
- "title": "Autosomal Dominant Tubulointerstitial Kidney Disease \u2013 MUC1",
- "type": "chapter",
- "doi": "",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/28359739",
+ "title": "2,4 DNP improves motor function, preserves medium spiny neuronal identity, and reduces oxidative stress in a mouse model of Huntington's disease.",
+ "type": "article-journal",
+ "doi": "10.1016/j.expneurol.2017.03.020",
"authors": [
- ["Anthony J.", "Bleyer"],
- ["Martina", "\u017divn\u00e1"],
- ["Kendrah", "Kidd"],
- ["Stanislav", "Kmoch"]
+ ["Bin", "Wu"],
+ ["Mali", "Jiang"],
+ ["Qi", "Peng"],
+ ["Gang", "Li"],
+ ["Zhipeng", "Hou"],
+ ["Ginger L", "Milne"],
+ ["Susumu", "Mori"],
+ ["Robert", "Alonso"],
+ ["John G", "Geisler"],
+ ["Wenzhen", "Duan"]
],
- "publisher": "GeneReviews\u00ae",
- "issn": "",
- "date": "1993-01-01",
- "abstract": "Autosomal dominant tubulointerstitial kidney disease \u2013 MUC1 (ADTKD-MUC1) is characterized by slowly progressive tubulointerstitial disease that leads to end-stage renal disease (ESRD) and the need for dialysis or kidney transplantation. The rate of loss of kidney function for individuals is variable within and between families, with a median age of onset of end-stage renal disease (ESRD) of 46 years (range: ages 20-70 years). There are no other systemic manifestations., The diagnosis of ADTKD-MUC1 is established in a proband with suggestive clinical findings and molecular genetic testing that reveals a heterozygous pathogenic variant in MUC1 that results in the creation of a specific frameshift protein (MUC1fs) responsible for the pathogenic changes in this disorder., Treatment of manifestations: Treatment follows standard guidelines for chronic kidney disease \u2013 based on the level of the serum creatinine and the estimated glomerular filtration rate (eGFR) \u2013 and its sequelae, which can include hypertension, anemia, and gout. Affected individuals are encouraged to prepare for kidney transplantation, the definitive treatment of ADTKD-MUC1, by staying in optimal health (e.g., by exercising, avoiding obesity and tobacco usage, and maintaining strict control of hypertension, dyslipidemia, and other cardiovascular risk factors). Kidney transplantation is curative; the outcome is excellent. Surveillance: Measurement of hemoglobin, serum concentrations of uric acid and creatinine and blood pressure annually prior to entering CKD Stage 3. Thereafter, follow up is determined by the treating nephrologist. Agents/circumstances to avoid: Affected individuals should follow general recommendations for chronic kidney disease. Pregnancy management: The use of ACE inhibitors should be avoided during pregnancy, as they can result in fetal damage and death. Women who are pregnant, planning a pregnancy, or not actively avoiding pregnancy should be transitioned to another antihypertensive medication. Allopurinol therapy should be stopped during pregnancy, if possible. Evaluation of relatives at risk: For early diagnosis and treatment: It is appropriate to identify as early as possible apparently asymptomatic at-risk adult relatives who have the familial MUC1 variant in order to monitor their serum creatinine levels and promptly initiate treatment and awareness of agents/circumstances to avoid. For kidney donation: Any relative who is a potential kidney donor should undergo molecular genetic testing to clarify the relative's genetic status so that only those who do not have the familial MUC1 pathogenic variant are evaluated further., ADTKD-MUC1 is inherited in an autosomal dominant manner. Each child of an affected individual has a 50% chance of inheriting the MUC1 pathogenic variant. Prenatal testing for MUC1 pathogenic variants is not available in the US at this time.",
- "language": "eng",
- "note": "PMID: 23946964\nThis CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: url:https://www.ncbi.nlm.nih.gov/books/NBK153723"
-},
-{
- "id": "genereviews:NBK1126",
- "manubot_success": false,
- "link": "https://www.ncbi.nlm.nih.gov/books/NBK1126",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'url:https://www.ncbi.nlm.nih.gov/books/NBK1126']' timed out after 3 seconds"
-},
-{
- "id": "genereviews:NBK1427",
- "manubot_success": false,
- "link": "https://www.ncbi.nlm.nih.gov/books/NBK1427",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'url:https://www.ncbi.nlm.nih.gov/books/NBK1427']' timed out after 3 seconds"
+ "publisher": "Experimental neurology",
+ "issn": "1090-2430",
+ "date": "2017-03-28",
+ "abstract": "Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in the first exon of the gene huntingtin. There is no treatment to prevent or delay the disease course of HD currently. Oxidative stress and mitochondrial dysfunction have emerged as key determinants of the disease progression in HD. Therefore, counteracting mutant huntingtin (mHtt)-induced oxidative stress and mitochondrial dysfunction appears as a new approach to treat this devastating disease. Interestingly, mild mitochondrial uncoupling improves neuronal resistance to stress and facilitates neuronal survival. Mild mitochondrial uncoupling can be induced by the proper dose of 2,4-dinitrophenol (DNP), a proton ionophore that was previously used for weight loss. In this study, we evaluated the effects of chronic administration of DNP at three doses (0.5, 1, 5mg/kg/day) on mHtt-induced behavioral deficits and cellular abnormalities in the N171-82Q HD mouse model. DNP at a low dose (1mg/kg/day) significantly improved motor function and preserved medium spiny neuronal marker DARPP32 and postsynaptic protein PSD95 in the striatum of HD mice. Further mechanistic study suggests that DNP at this dose reduced oxidative stress in HD mice, which was indicated by reduced levels of F2-isoprostanes in the brain of HD mice treated with DNP. Our data indicated that DNP provided behavioral benefit and neuroprotective effect at a weight neutral dose in HD mice, suggesting that the potential value of repositioning DNP to HD treatment is warranted in well-controlled clinical trials in HD.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28359739"
},
{
- "id": "genereviews:NBK1513",
- "manubot_success": false,
- "link": "https://www.ncbi.nlm.nih.gov/books/NBK1513",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'url:https://www.ncbi.nlm.nih.gov/books/NBK1513']' timed out after 3 seconds"
+ "id": "pmid:28205498",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/28205498",
+ "title": "Cognitive Control, Learning, and Clinical Motor Ratings Are Most Highly Associated with Basal Ganglia Brain Volumes in the Premanifest Huntington's Disease Phenotype.",
+ "type": "article-journal",
+ "doi": "10.1017/s1355617716001132",
+ "authors": [
+ ["Maria B", "Misiura"],
+ ["Spencer", "Lourens"],
+ ["Vince D", "Calhoun"],
+ ["Jeffrey", "Long"],
+ ["Jeremy", "Bockholt"],
+ ["Hans", "Johnson"],
+ ["Ying", "Zhang"],
+ ["Jane S", "Paulsen"],
+ ["Jessica A", "Turner"],
+ ["Jingyu", "Liu"],
+ ["Betul", "Kara"],
+ ["Elizabeth", "Fall"]
+ ],
+ "publisher": "Journal of the International Neuropsychological Society : JINS",
+ "issn": "1469-7661",
+ "date": "2017-02-01",
+ "abstract": "Huntington's disease (HD) is a debilitating genetic disorder characterized by motor, cognitive and psychiatric abnormalities associated with neuropathological decline. HD pathology is the result of an extended chain of CAG (cytosine, adenine, guanine) trinucleotide repetitions in the HTT gene. Clinical diagnosis of HD requires the presence of an otherwise unexplained extrapyramidal movement disorder in a participant at risk for HD. Over the past 15 years, evidence has shown that cognitive, psychiatric, and subtle motor dysfunction is evident decades before traditional motor diagnosis. This study examines the relationships among subcortical brain volumes and measures of emerging disease phenotype in prodromal HD, before clinical diagnosis.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28205498"
},
{
- "id": "genereviews:NBK1438",
+ "id": "pmid:28202696",
"manubot_success": true,
- "link": "http://www.ncbi.nlm.nih.gov/books/NBK1438/",
- "title": "Spinocerebellar Ataxia Type 17",
- "type": "chapter",
- "doi": "",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/28202696",
+ "title": "Low cancer prevalence in polyglutamine expansion diseases.",
+ "type": "article-journal",
+ "doi": "10.1212/wnl.0000000000003725",
"authors": [
- ["Yasuko", "Toyoshima"],
- ["Osamu", "Onodera"],
- ["Mitsunori", "Yamada"],
- ["Shoji", "Tsuji"],
- ["Hitoshi", "Takahashi"]
+ ["Giulia", "Coarelli"],
+ ["Alhassane", "Diallo"],
+ ["Morgane Sonia", "Thion"],
+ ["Daisy", "Rinaldi"],
+ ["Fabienne", "Calvas"],
+ ["Ouahid Lagha", "Boukbiza"],
+ ["Alina", "Tataru"],
+ ["Perrine", "Charles"],
+ ["Christine", "Tranchant"],
+ ["Cecilia", "Marelli"],
+ ["Claire", "Ewenczyk"],
+ ["Maya", "Tchikviladz\u00e9"],
+ ["Marie-Lorraine", "Monin"],
+ ["Bertrand", "Carlander"],
+ ["Mathieu", "Anheim"],
+ ["Alexis", "Brice"],
+ ["Fanny", "Mochel"],
+ ["Sophie", "Tezenas du Montcel"],
+ ["Sandrine", "Humbert"],
+ ["Alexandra", "Durr"]
],
- "publisher": "GeneReviews\u00ae",
- "issn": "",
- "date": "1993-01-01",
- "abstract": "Spinocerebellar ataxia type 17 (SCA17) is characterized by ataxia, dementia, and involuntary movements, including chorea and dystonia. Psychiatric symptoms, pyramidal signs, and rigidity are common. The age of onset ranges from three to 55 years. Individuals with full-penetrance alleles develop neurologic and/or psychiatric symptoms by age 50 years. Ataxia and psychiatric abnormalities are frequently the initial findings, followed by involuntary movement, parkinsonism, dementia, and pyramidal signs. Brain MRI shows variable atrophy of the cerebrum, brain stem, and cerebellum. The clinical features correlate with the length of the polyglutamine expansion but are not absolutely predictive of the clinical course., The diagnosis of SCA17 is established in a proband by identification of an abnormal CAG/CAA repeat expansion in TBP. Affected individuals usually have more than 41 repeats. The CAA and CAG codons both encode glutamine residues resulting in a pathogenic polyglutamine expansion., Treatment of manifestations: Psychotropic medications for psychiatric issues, anti-seizure medication for seizures (ASM); botulinum toxin injections for dystonia; adaptation of the environment to accommodate dementia. Prevention of secondary complications: Side effects of psychotropic medications and ASMs may require total or intermittent discontinuation of the treatment or reduction in dose. Surveillance: Annual or semiannual evaluation by a neurologist or more frequently if symptoms are progressing rapidly. Agents/circumstances to avoid: Sedative/hypnotic agents, such as ethanol or certain medications, may exacerbate incoordination., SCA17 is inherited in an autosomal dominant manner. Offspring of affected individuals are at a 50% risk of inheriting the expanded TBP allele. The age of onset, severity, specific symptoms, and progression of the disease are variable and cannot be precisely predicted by family history or size of expansion. Prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible if the diagnosis has been established in an affected family member by molecular genetic testing.",
- "language": "eng",
- "note": "PMID: 20301611\nThis CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: url:https://www.ncbi.nlm.nih.gov/books/NBK1438"
+ "publisher": "Neurology",
+ "issn": "1526-632X",
+ "date": "2017-02-15",
+ "abstract": "Polyglutamine (PolyQ) diseases are dominantly transmitted neurologic disorders, caused by coding and expanded CAG trinucleotide repeats. Cancer was reported retrospectively to be rare in patients with PolyQ diseases and we aimed to investigate its prevalence in France.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28202696"
},
{
- "id": "genereviews:NBK1530",
- "manubot_success": false,
- "link": "https://www.ncbi.nlm.nih.gov/books/NBK1530",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'url:https://www.ncbi.nlm.nih.gov/books/NBK1530']' timed out after 3 seconds"
+ "id": "pmid:28153533",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/28153533",
+ "title": "Dysregulation of gene expression in the striatum of BACHD rats expressing full-length mutant huntingtin and associated abnormalities on molecular and protein levels.",
+ "type": "article-journal",
+ "doi": "10.1016/j.neuropharm.2017.01.029",
+ "authors": [
+ ["Libo", "Yu-Taeger"],
+ ["Michael", "Bonin"],
+ ["Janice", "Stricker-Shaver"],
+ ["Olaf", "Riess"],
+ ["Hoa Huu Phuc", "Nguyen"]
+ ],
+ "publisher": "Neuropharmacology",
+ "issn": "1873-7064",
+ "date": "2017-01-30",
+ "abstract": "Huntington disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the gene coding for the huntingtin protein (HTT). Mutant HTT (mHTT) has been proposed to cause neuronal dysfunction and neuronal loss through multiple mechanisms. Transcriptional changes may be a core pathogenic feature of HD. Utilizing the Affymetrix platform we performed a genome-wide RNA expression analysis in two BACHD transgenic rat lines (TG5 and TG9) at 12 months of age, both of which carry full-length human mHTT but with different expression levels. By defining the threshold of significance at p\u00a0<\u00a00.01, we found 1608 genes and 871 genes differentially expressed in both TG5 and TG9 rats when compared to the wild type littermates, respectively. We only chose the highly up-/down-regulated genes for further analysis by setting an additional threshold of 1.5 fold change. Comparing gene expression profiles of human HD brains and BACHD rats revealed a high concordance in both functional and IPA (Ingenuity Pathway Analysis) canonical pathways relevant to HD. In addition, we investigated the causes leading to gene expression changes at molecular and protein levels in BACHD rats including the involvement of polyQ-containing transcription factors TATA box-binding protein (TBP), Sp1 and CBP as well as the chromatin structure. We demonstrate that the BACHD rat model recapitulates the gene expression changes of the human disease supporting its role as a preclinical research animal model. We also show for the first time that TFIID complex formation is reduced, while soluble TBP is increased in an HD model. This finding suggests that mHTT is a competitor instead of a recruiter of polyQ-containing transcription factors in the transcription process in HD.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28153533"
},
{
- "id": "pmid:12764052",
+ "id": "pmid:28000697",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/12764052",
- "title": "A novel autosomal dominant spinocerebellar ataxia (SCA22) linked to chromosome 1p21-q23.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/28000697",
+ "title": "The targetable A1 Huntington disease haplotype has distinct Amerindian and European origins in Latin America.",
"type": "article-journal",
- "doi": "10.1093/brain/awg130",
+ "doi": "10.1038/ejhg.2016.169",
"authors": [
- ["Ming-Yi", "Chung"],
- ["Yi-Chun", "Lu"],
- ["Nai-Chia", "Cheng"],
- ["Bing-Wen", "Soong"]
+ ["Chris", "Kay"],
+ ["Indira", "Tirado-Hurtado"],
+ ["Mario", "Cornejo-Olivas"],
+ ["Jennifer A", "Collins"],
+ ["Galen", "Wright"],
+ ["Miguel", "Inca-Martinez"],
+ ["Diego", "Veliz-Otani"],
+ ["Maria E", "Ketelaar"],
+ ["Ramy A", "Slama"],
+ ["Colin J", "Ross"],
+ ["Pilar", "Mazzetti"],
+ ["Michael R", "Hayden"]
],
- "publisher": "Brain : a journal of neurology",
- "issn": "0006-8950",
- "date": "2003-06-01",
- "abstract": "The autosomal dominant cerebellar ataxias (ADCA) are a clinically, pathologically and genetically heterogeneous group of disorders. Ten responsible genes have been identified for spinocerebellar ataxia types SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA10, SCA12 and SCA17, and dentatorubral pallidoluysian atrophy (DRPLA). The mutation is caused by an expansion of a CAG, CTG or ATTCT repeat sequence of these genes. Six additional loci, SCA4, SCA5, SCA11, SCA13, SCA14 and SCA16 have also been mapped. The growing heterogeneity of the autosomal dominant forms of these diseases shows that the genetic aetiologies of at least 20% of ADCA have yet to be elucidated. We ascertained and clinically characterized a four-generation Chinese pedigree segregating an autosomal dominant phenotype for cerebellar ataxia. Direct mutation analysis, linkage analysis for all known SCA loci and a genome-wide linkage study were performed. Direct mutation analysis excluded SCA1, 2, 3, 6, 7, 8, 10, 12, 17 and DRPLA, and genetic linkage analysis excluded SCA4, 5, 11, 13, 14 and 16. The genome-wide linkage study suggested linkage to a locus on chromosome 1p21-q23, with the highest two-point LOD score at D1S1167 (Zmax = 3.46 at theta = 0.00). Multipoint analysis and haplotype reconstruction traced this novel SCA locus (SCA22) to a 43.7-cM interval flanked by D1S206 and D1S2878 (Zmax = 3.78 under four liability classes, and 2.67 using affected-only method). The age at onset ranged from 10 to 46 years. All affected members had gait ataxia with variable features of dysarthria and hyporeflexia. Head MRI showed homogeneous atrophy of the cerebellum without involvement of the brainstem. In six parent-child pairs, median onset occurred 10 years earlier in offspring than in their parents, suggesting anticipation. This family is distinct from other families with SCA and is characterized by a slowly progressive, pure cerebellar ataxia.",
+ "publisher": "European journal of human genetics : EJHG",
+ "issn": "1476-5438",
+ "date": "2016-12-21",
+ "abstract": "Huntington disease (HD) is a dominant neurodegenerative disorder caused by a CAG repeat expansion in the Huntingtin (HTT) gene. HD occurs worldwide, but the causative mutation is found on different HTT haplotypes in distinct ethnic groups. In Latin America, HD is thought to have European origins, but indigenous Amerindian ancestry has not been investigated. Here, we report dense HTT haplotypes in 62 mestizo Peruvian HD families, 17 HD families from across Latin America, and 42 controls of defined Peruvian Amerindian ethnicity to determine the origin of HD in populations of admixed Amerindian and European descent. HD in Peru occurs most frequently on the A1 HTT haplotype (73%), as in Europe, but on an unexpected indigenous variant also found in Amerindian controls. This Amerindian A1 HTT haplotype predominates over the European A1 variant among geographically disparate Latin American controls and in HD families from across Latin America, supporting an indigenous origin of the HD mutation in mestizo American populations. We also show that a proportion of HD mutations in Peru occur on a C1 HTT haplotype of putative Amerindian origin (14%). The majority of HD mutations in Latin America may therefore occur on haplotypes of Amerindian ancestry rather than on haplotypes resulting from European admixture. Despite the distinct ethnic ancestry of Amerindian and European A1 HTT, alleles on the parent A1 HTT haplotype allow for development of identical antisense molecules to selectively silence the HD mutation in the greatest proportion of patients in both Latin American and European populations.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12764052"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28000697"
},
{
- "id": "pmid:28444220",
+ "id": "pmid:27983559",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/28444220",
- "title": "A panel study on patients with dominant cerebellar ataxia highlights the frequency of channelopathies.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27983559",
+ "title": "Phenotype Characterization of HD Intermediate Alleles in PREDICT-HD.",
"type": "article-journal",
- "doi": "10.1093/brain/awx081",
+ "doi": "10.3233/jhd-160185",
"authors": [
- ["Marie", "Coutelier"],
- ["Giulia", "Coarelli"],
- ["Marie-Lorraine", "Monin"],
- ["Juliette", "Konop"],
- ["Claire-Sophie", "Davoine"],
- ["Christelle", "Tesson"],
- ["R\u00e9mi", "Valter"],
- ["Mathieu", "Anheim"],
- ["Anthony", "Behin"],
- ["Giovanni", "Castelnovo"],
- ["Perrine", "Charles"],
- ["Albert", "David"],
- ["Claire", "Ewenczyk"],
- ["M\u00e9lanie", "Fradin"],
- ["Cyril", "Goizet"],
- ["Didier", "Hannequin"],
- ["Pierre", "Labauge"],
- ["Florence", "Riant"],
- ["Pierre", "Sarda"],
- ["Yves", "Sznajer"],
- ["Fran\u00e7ois", "Tison"],
- ["Urielle", "Ullmann"],
- ["Lionel", "Van Maldergem"],
- ["Fanny", "Mochel"],
- ["Alexis", "Brice"],
- ["Giovanni", "Stevanin"],
- ["Alexandra", "Durr"]
+ ["Nancy R", "Downing"],
+ ["Spencer", "Lourens"],
+ ["Isabella", "De Soriano"],
+ ["Jeffrey D", "Long"],
+ ["Jane S", "Paulsen"]
],
- "publisher": "Brain : a journal of neurology",
- "issn": "1460-2156",
- "date": "2017-06-01",
- "abstract": "Autosomal dominant cerebellar ataxias have a marked heterogeneous genetic background, with mutations in 34 genes identified so far. This large amount of implicated genes accounts for heterogeneous clinical presentations, making genotype-phenotype correlations a major challenge in the field. While polyglutamine ataxias, linked to CAG repeat expansions in genes such as ATXN1, ATXN2, ATXN3, ATXN7, CACNA1A and TBP, have been extensively characterized in large cohorts, there is a need for comprehensive assessment of frequency and phenotype of more 'conventional' ataxias. After exclusion of CAG/polyglutamine expansions in spinocerebellar ataxia genes in 412 index cases with dominantly inherited cerebellar ataxias, we aimed to establish the relative frequencies of mutations in other genes, with an approach combining panel sequencing and TaqMan\u00ae polymerase chain reaction assay. We found relevant genetic variants in 59 patients (14.3%). The most frequently mutated were channel genes [CACNA1A (n = 16), KCND3 (n = 4), KCNC3 (n = 2) and KCNA1 (n = 2)]. Deletions in ITPR1 (n = 11) were followed by biallelic variants in SPG7 (n = 9). Variants in AFG3L2 (n = 7) came next in frequency, and variants were rarely found in STBN2 (n = 2), ELOVL5, FGF14, STUB1 and TTBK2 (n = 1 each). Interestingly, possible risk factor variants were detected in SPG7 and POLG. Clinical comparisons showed that ataxias due to channelopathies had a significantly earlier age at onset with an average of 24.6 years, versus 40.9 years for polyglutamine expansion spinocerebellar ataxias and 37.8 years for SPG7-related forms (P = 0.001). In contrast, disease duration was significantly longer in the former (20.5 years versus 9.3 and 13.7, P=0.001), though for similar functional stages, indicating slower progression of the disease. Of interest, intellectual deficiency was more frequent in channel spinocerebellar ataxias, while cognitive impairment in adulthood was similar among the three groups. Similar differences were found among a single gene group, comparing 23 patients with CACNA1A expansions (spinocerebellar ataxia 6) to 22 patients with CACNA1A point mutations, which had lower average age at onset (25.2 versus 47.3 years) with longer disease duration (18.7 versus 10.9), but lower severity indexes (0.39 versus 0.44), indicating slower progression of the disease. In conclusion, we identified relevant genetic variations in up to 15% of cases after exclusion of polyglutamine expansion spinocerebellar ataxias, and confirmed CACNA1A and SPG7 as major ataxia genes. We could delineate firm genotype-phenotype correlations that are important for genetic counselling and of possible prognostic value.",
+ "publisher": "Journal of Huntington's disease",
+ "issn": "1879-6400",
+ "date": "2016-12-15",
+ "abstract": "Huntington disease (HD) is a neurodegenerative disease caused by a CAG repeat expansion on chromosome 4. Pathology is associated with CAG repeat length. Prior studies examining people in the intermediate allele (IA) range found subtle differences in motor, cognitive, and behavioral domains compared to controls.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28444220"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27983559"
},
{
- "id": "pmid:30109267",
+ "id": "pmid:27870408",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/30109267",
- "title": "Noncoding repeat expansions for ALS in Japan are associated with the",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27870408",
+ "title": "Sex-specific effects of the Huntington gene on normal neurodevelopment.",
"type": "article-journal",
- "doi": "10.1212/nxg.0000000000000252",
+ "doi": "10.1002/jnr.23980",
"authors": [
- ["Makito", "Hirano"],
- ["Makoto", "Samukawa"],
- ["Chiharu", "Isono"],
- ["Kazumasa", "Saigoh"],
- ["Yusaku", "Nakamura"],
- ["Susumu", "Kusunoki"]
+ ["Jessica K", "Lee"],
+ ["Yue", "Ding"],
+ ["Amy L", "Conrad"],
+ ["Elena", "Cattaneo"],
+ ["Eric", "Epping"],
+ ["Kathy", "Mathews"],
+ ["Pedro", "Gonzalez-Alegre"],
+ ["Larry", "Cahill"],
+ ["Vincent", "Magnotta"],
+ ["Bradley L", "Schlaggar"],
+ ["Joel S", "Perlmutter"],
+ ["Regina E Y", "Kim"],
+ ["Jeffrey D", "Dawson"],
+ ["Peg", "Nopoulos"]
],
- "publisher": "Neurology. Genetics",
- "issn": "2376-7839",
- "date": "2018-08-01",
- "abstract": "To assess the contribution of noncoding repeat expansions in Japanese patients with amyotrophic lateral sclerosis (ALS).",
+ "publisher": "Journal of neuroscience research",
+ "issn": "1097-4547",
+ "date": "2017-01-02",
+ "abstract": "Huntington disease is a neurodegenerative disorder caused by a gene (HTT) with a unique feature of trinucleotide repeats ranging from 10 to 35 in healthy people; when expanded beyond 39 repeats, Huntington disease develops. Animal models demonstrate that HTT is vital to brain development; however, this has not been studied in humans. Moreover, evidence suggests that triplet repeat genes may have been vital in evolution of the human brain. Here we evaluate brain structure using magnetic resonance imaging and brain function using cognitive tests in a sample of school-aged children ages 6 to 18 years old. DNA samples were processed to quantify the number of CAG repeats within HTT. We find that the number of repeats in HTT, below disease threshold, confers advantageous changes in brain structure and general intelligence (IQ): the higher the number of repeats, the greater the change in brain structure, and the higher the IQ. The pattern of structural brain changes associated with HTT is strikingly different between males and females. HTT may confer an advantage or a disadvantage depending on the repeat length, playing a key role in either the evolution of a superior human brain or development of a uniquely human brain disease. \u00a9 2016 Wiley Periodicals, Inc.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30109267"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27870408"
},
{
- "id": "pmid:39913612",
+ "id": "pmid:27681197",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/39913612",
- "title": "ALS plasma biomarkers reveal neurofilament and pTau correlate with disease onset and progression.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27681197",
+ "title": "Mycobacterium tuberculosis multi-drug-resistant strain M induces IL-17",
"type": "article-journal",
- "doi": "10.1002/acn3.70001",
+ "doi": "10.1111/cei.12873",
"authors": [
- ["Eleanor V", "Thomas"],
- ["Changee", "Han"],
- ["Woo Jae", "Kim"],
- ["Seneshaw", "Asress"],
- ["Yingjie", "Li"],
- ["Jennifer A", "Taylor"],
- ["Marla", "Gearing"],
- ["Christina N", "Fournier"],
- ["Zachary T", "McEachin"],
- ["Nicholas T", "Seyfried"],
- ["Jonathan D", "Glass"]
+ ["J I", "Basile"],
+ ["D", "Kviatcovsky"],
+ ["M M", "Romero"],
+ ["L", "Balboa"],
+ ["J", "Monteserin"],
+ ["V", "Ritacco"],
+ ["B", "Lopez"],
+ ["C", "Sabio y Garc\u00eda"],
+ ["A", "Garc\u00eda"],
+ ["M", "Vescovo"],
+ ["P G", "Montaner"],
+ ["D", "Palmero"],
+ ["M", "Del Carmen Sasiain"],
+ ["S", "de la Barrera"]
],
- "publisher": "Annals of clinical and translational neurology",
- "issn": "2328-9503",
- "date": "2025-02-06",
- "abstract": "We performed a pilot screen to assess the utility of the NULISA\u2122 (Nucleic-acid-Linked Immuno-Sandwich Assay) platform in the identification of amyotrophic lateral sclerosis (ALS) biomarkers.",
+ "publisher": "Clinical and experimental immunology",
+ "issn": "1365-2249",
+ "date": "2016-11-02",
+ "abstract": "We have reported previously that T cells from patients with multi-drug-resistant tuberculosis (MDR-TB) express high levels of interleukin (IL)-17 in response to the MDR strain M (Haarlem family) of Mycobacterium tuberculosis (M. tuberculosis). Herein, we explore the pathways involved in the induction of Th17 cells in MDR-TB patients and healthy tuberculin reactors [purified protein derivative healthy donors (PPD",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39913612"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27681197"
},
{
- "id": "pmid:34687211",
+ "id": "pmid:27740685",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/34687211",
- "title": "SLITRK2, an X-linked modifier of the age at onset in C9orf72 frontotemporal lobar degeneration.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27740685",
+ "title": "Factors related to genetic testing in adults at risk for Huntington disease: the prospective Huntington at-risk observational study (PHAROS).",
"type": "article-journal",
- "doi": "10.1093/brain/awab171",
+ "doi": "10.1111/cge.12893",
"authors": [
- ["Mathieu", "Barbier"],
- ["Agn\u00e8s", "Camuzat"],
- ["Khalid El", "Hachimi"],
- ["Justine", "Guegan"],
- ["Daisy", "Rinaldi"],
- ["Serena", "Lattante"],
- ["Marion", "Houot"],
- ["Raquel", "S\u00e1nchez-Valle"],
- ["Mario", "Sabatelli"],
- ["Anna", "Antonell"],
- ["Laura", "Molina-Porcel"],
- ["Fabienne", "Clot"],
- ["Philippe", "Couratier"],
- ["Emma", "van der Ende"],
- ["Julie", "van der Zee"],
- ["Claudia", "Manzoni"],
- ["William", "Camu"],
- ["C\u00e9cile", "Cazeneuve"],
- ["Fran\u00e7ois", "Sellal"],
- ["Mira", "Didic"],
- ["V\u00e9ronique", "Golfier"],
- ["Florence", "Pasquier"],
- ["Charles", "Duyckaerts"],
- ["Giacomina", "Rossi"],
- ["Amalia C", "Bruni"],
- ["Victoria", "Alvarez"],
- ["Estrella", "G\u00f3mez-Tortosa"],
- ["Alexandre", "de Mendon\u00e7a"],
- ["Caroline", "Graff"],
- ["Mario", "Masellis"],
- ["Benedetta", "Nacmias"],
- ["Badreddine Mohand", "Oumoussa"],
- ["Ludmila", "Jornea"],
- ["Sylvie", "Forlani"],
- ["Viviana", "Van Deerlin"],
- ["Jonathan D", "Rohrer"],
- ["Ellen", "Gelpi"],
- ["Rosa", "Rademakers"],
- ["John", "Van Swieten"],
- ["Eric", "Le Guern"],
- ["Christine", "Van Broeckhoven"],
- ["Raffaele", "Ferrari"],
- ["Emmanuelle", "G\u00e9nin"],
- ["Alexis", "Brice"],
- ["Isabelle", "Le Ber"]
+ ["K A", "Quaid"],
+ ["S W", "Eberly"],
+ ["E", "Kayson-Rubin"],
+ ["D", "Oakes"],
+ ["I", "Shoulson"]
+ ],
+ "publisher": "Clinical genetics",
+ "issn": "1399-0004",
+ "date": "2016-11-24",
+ "abstract": "Huntington disease (HD) is a late onset ultimately fatal neurodegenerative disorder caused by a cytosine-adenine-guanine ( CAG) triplet repeat expansion in the Huntingtin gene which was discovered in 1993. The PHAROS study is a unique observational study of 1001 individuals at risk for HD who had not been previously tested for HD and who had no plans to do so. In this cohort, 104 (10%) individuals changed their minds and chose to be tested during the course of the study but outside of the study protocol. Baseline behavioral scores, especially apathy, were more strongly associated with later genetic testing than motor and chorea scores, particularly among subjects with expanded CAG repeat length. In the CAG expanded group, those choosing to be tested were older and had more chorea and higher scores on the behavioral section of the unified Huntington's disease rating scale at baseline than those not choosing to be tested. Following genetic testing, 56% of subjects with CAG < 37 had less depression when compared to prior to testing, but depression generally stayed the same or increased for 64% of subjects in the expanded group. This finding suggests that approaches to testing must continue to be cautious, with appropriate medical, psychological and social support.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27740685"
+},
+{
+ "id": "pmid:27689620",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27689620",
+ "title": "Cellular Analysis of Silencing the\u00a0Huntington's Disease Gene Using AAV9\u00a0Mediated Delivery of Artificial Micro\u00a0RNA into the Striatum of\u00a0Q140/Q140\u00a0Mice.",
+ "type": "article-journal",
+ "doi": "10.3233/jhd-160215",
+ "authors": [
+ ["Allison M", "Keeler"],
+ ["Ellen", "Sapp"],
+ ["Kathryn", "Chase"],
+ ["Emily", "Sottosanti"],
+ ["Eric", "Danielson"],
+ ["Edith", "Pfister"],
+ ["Lorelei", "Stoica"],
+ ["Marian", "DiFiglia"],
+ ["Neil", "Aronin"],
+ ["Miguel", "Sena-Esteves"]
],
- "publisher": "Brain : a journal of neurology",
- "issn": "1460-2156",
- "date": "2021-10-22",
- "abstract": "The G4C2-repeat expansion in C9orf72 is the most common cause of frontotemporal dementia and of amyotrophic lateral sclerosis. The variability of age at onset and phenotypic presentations is a hallmark of C9orf72 disease. In this study, we aimed to identify modifying factors of disease onset in C9orf72 carriers using a family-based approach, in pairs of C9orf72 carrier relatives with concordant or discordant age at onset. Linkage and association analyses provided converging evidence for a locus on chromosome Xq27.3. The minor allele A of rs1009776 was associated with an earlier onset (P\u2009=\u20091 \u00d7 10-5). The association with onset of dementia was replicated in an independent cohort of unrelated C9orf72 patients (P\u2009=\u20090.009). The protective major allele delayed the onset of dementia from 5 to 13\u2009years on average depending on the cohort considered. The same trend was observed in an independent cohort of C9orf72 patients with extreme deviation of the age at onset (P\u2009=\u20090.055). No association of rs1009776 was detected in GRN patients, suggesting that the effect of rs1009776 was restricted to the onset of dementia due to C9orf72. The minor allele A is associated with a higher SLITRK2 expression based on both expression quantitative trait loci (eQTL) databases and in-house expression studies performed on C9orf72 brain tissues. SLITRK2 encodes for a post-synaptic adhesion protein. We further show that synaptic vesicle glycoprotein 2 and synaptophysin, two synaptic vesicle proteins, were decreased in frontal cortex of C9orf72 patients carrying the minor allele. Upregulation of SLITRK2 might be associated with synaptic dysfunctions and drives adverse effects in C9orf72 patients that could be modulated in those carrying the protective allele. How the modulation of SLITRK2 expression affects synaptic functions and influences the disease onset of dementia in C9orf72 carriers will require further investigations. In summary, this study describes an original approach to detect modifier genes in rare diseases and reinforces rising links between C9orf72 and synaptic dysfunctions that might directly influence the occurrence of first symptoms.",
+ "publisher": "Journal of Huntington's disease",
+ "issn": "1879-6400",
+ "date": "2016-10-01",
+ "abstract": "The genetic mutation in Huntington's disease (HD) is a\u00a0CAG repeat expansion in the coding region of the huntingtin (Htt) gene. RNAi strategies have proven effective in substantially down-regulating Htt mRNA in the striatum through delivery of siRNAs or viral vectors based on whole tissue assays, but the extent of htt mRNA lowering in individual neurons is unknown.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34687211"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27689620"
},
{
- "id": "pmid:30347338",
+ "id": "pmid:27658206",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/30347338",
- "title": "Response to the commentary \"The effect of C9orf72 intermediate repeat expansions in neurodegenerative and autoimmune diseases\" by Biasiotto G and Zanella I.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27658206",
+ "title": "Polyglutamine Tract Expansion Increases S-Nitrosylation of Huntingtin and Ataxin-1.",
"type": "article-journal",
- "doi": "10.1016/j.msard.2018.10.007",
+ "doi": "10.1371/journal.pone.0163359",
"authors": [
- ["Cinzia", "Tiloca"],
- ["Melissa", "Sorosina"],
- ["Federica", "Esposito"],
- ["Silvia", "Peroni"],
- ["Claudia", "Colombrita"],
- ["Nicola", "Ticozzi"],
- ["Antonia", "Ratti"],
- ["Filippo", "Martinelli-Boneschi"],
- ["Vincenzo", "Silani"]
+ ["Chun-Lun", "Ni"],
+ ["Divya", "Seth"],
+ ["Fabio Vasconcelos", "Fonseca"],
+ ["Liwen", "Wang"],
+ ["Tsan Sam", "Xiao"],
+ ["Phillip", "Gruber"],
+ ["Man-Sun", "Sy"],
+ ["Jonathan S", "Stamler"],
+ ["Alan M", "Tartakoff"]
],
- "publisher": "Multiple sclerosis and related disorders",
- "issn": "2211-0356",
- "date": "2018-10-14",
- "abstract": "",
+ "publisher": "PloS one",
+ "issn": "1932-6203",
+ "date": "2016-09-22",
+ "abstract": "Expansion of the polyglutamine (polyQ) tract in the huntingtin (Htt) protein causes Huntington's disease (HD), a fatal inherited movement disorder linked to neurodegeneration in the striatum and cortex. S-nitrosylation and S-acylation of cysteine residues regulate many functions of cytosolic proteins. We therefore used a resin-assisted capture approach to identify these modifications in Htt. In contrast to many proteins that have only a single S-nitrosylation or S-acylation site, we identified sites along much of the length of Htt. Moreover, analysis of cells expressing full-length Htt or a large N-terminal fragment of Htt shows that polyQ expansion strongly increases Htt S-nitrosylation. This effect appears to be general since it is also observed in Ataxin-1, which causes spinocerebellar ataxia type 1 (SCA1) when its polyQ tract is expanded. Overexpression of nitric oxide synthase increases the S-nitrosylation of normal Htt and the frequency of conspicuous juxtanuclear inclusions of Htt N-terminal fragments in transfected cells. Taken together with the evidence that S-nitrosylation of Htt is widespread and parallels polyQ expansion, these subcellular changes show that S-nitrosylation affects the biology of this protein in vivo.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30347338"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27658206"
},
{
- "id": "pmid:30252044",
+ "id": "pmid:27639545",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/30252044",
- "title": "A C6orf10/LOC101929163 locus is associated with age of onset in C9orf72 carriers.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27639545",
+ "title": "In vivo proof-of-concept of removal of the huntingtin caspase cleavage motif-encoding exon 12 approach in the YAC128 mouse model of Huntington's disease.",
"type": "article-journal",
- "doi": "10.1093/brain/awy238",
+ "doi": "10.1016/j.biopha.2016.09.007",
"authors": [
- ["Ming", "Zhang"],
- ["Raffaele", "Ferrari"],
- ["Maria Carmela", "Tartaglia"],
- ["Julia", "Keith"],
- ["Ezequiel I", "Surace"],
- ["Uri", "Wolf"],
- ["Christine", "Sato"],
- ["Mark", "Grinberg"],
- ["Yan", "Liang"],
- ["Zhengrui", "Xi"],
- ["Kyle", "Dupont"],
- ["Philip", "McGoldrick"],
- ["Anna", "Weichert"],
- ["Paul M", "McKeever"],
- ["Raphael", "Schneider"],
- ["Michael D", "McCorkindale"],
- ["Claudia", "Manzoni"],
- ["Rosa", "Rademakers"],
- ["Neill R", "Graff-Radford"],
- ["Dennis W", "Dickson"],
- ["Joseph E", "Parisi"],
- ["Bradley F", "Boeve"],
- ["Ronald C", "Petersen"],
- ["Bruce L", "Miller"],
- ["William W", "Seeley"],
- ["John C", "van Swieten"],
- ["Jeroen", "van Rooij"],
- ["Yolande", "Pijnenburg"],
- ["Julie", "van der Zee"],
- ["Christine", "Van Broeckhoven"],
- ["Isabelle", "Le Ber"],
- ["Vivianna", "Van Deerlin"],
- ["EunRan", "Suh"],
- ["Jonathan D", "Rohrer"],
- ["Simon", "Mead"],
- ["Caroline", "Graff"],
- ["Linn", "\u00d6ijerstedt"],
- ["Stuart", "Pickering-Brown"],
- ["Sara", "Rollinson"],
- ["Giacomina", "Rossi"],
- ["Fabrizio", "Tagliavini"],
- ["William S", "Brooks"],
- ["Carol", "Dobson-Stone"],
- ["Glenda M", "Halliday"],
- ["John R", "Hodges"],
- ["Olivier", "Piguet"],
- ["Giuliano", "Binetti"],
- ["Luisa", "Benussi"],
- ["Roberta", "Ghidoni"],
- ["Benedetta", "Nacmias"],
- ["Sandro", "Sorbi"],
- ["Amalia C", "Bruni"],
- ["Daniela", "Galimberti"],
- ["Elio", "Scarpini"],
- ["Innocenzo", "Rainero"],
- ["Elisa", "Rubino"],
- ["Jordi", "Clarimon"],
- ["Alberto", "Lle\u00f3"],
- ["Agustin", "Ruiz"],
- ["Isabel", "Hern\u00e1ndez"],
- ["Pau", "Pastor"],
- ["Monica", "Diez-Fairen"],
- ["Barbara", "Borroni"],
- ["Florence", "Pasquier"],
- ["Vincent", "Deramecourt"],
- ["Thibaud", "Lebouvier"],
- ["Robert", "Perneczky"],
- ["Janine", "Diehl-Schmid"],
- ["Jordan", "Grafman"],
- ["Edward D", "Huey"],
- ["Richard", "Mayeux"],
- ["Michael A", "Nalls"],
- ["Dena", "Hernandez"],
- ["Andrew", "Singleton"],
- ["Parastoo", "Momeni"],
- ["Zhen", "Zeng"],
- ["John", "Hardy"],
- ["Janice", "Robertson"],
- ["Lorne", "Zinman"],
- ["Ekaterina", "Rogaeva"]
+ ["Jo\u00e3o", "Casaca-Carreira"],
+ ["Lodewijk J A", "Toonen"],
+ ["Melvin M", "Evers"],
+ ["Ali", "Jahanshahi"],
+ ["Willeke M C", "van-Roon-Mom"],
+ ["Yasin", "Temel"]
],
- "publisher": "Brain : a journal of neurology",
- "issn": "1460-2156",
- "date": "2018-10-01",
- "abstract": "The G4C2-repeat expansion in C9orf72 is the most common known cause of amyotrophic lateral sclerosis and frontotemporal dementia. The high phenotypic heterogeneity of C9orf72 patients includes a wide range in age of onset, modifiers of which are largely unknown. Age of onset could be influenced by environmental and genetic factors both of which may trigger DNA methylation changes at CpG sites. We tested the hypothesis that age of onset in C9orf72 patients is associated with some common single nucleotide polymorphisms causing a gain or loss of CpG sites and thus resulting in DNA methylation alterations. Combined analyses of epigenetic and genetic data have the advantage of detecting functional variants with reduced likelihood of false negative results due to excessive correction for multiple testing in genome-wide association studies. First, we estimated the association between age of onset in C9orf72 patients (n = 46) and the DNA methylation levels at all 7603 CpG sites available on the 450 k BeadChip that are mapped to common single nucleotide polymorphisms. This was followed by a genetic association study of the discovery (n = 144) and replication (n = 187) C9orf72 cohorts. We found that age of onset was reproducibly associated with polymorphisms within a 124.7 kb linkage disequilibrium block tagged by top-significant variation, rs9357140, and containing two overlapping genes (LOC101929163 and C6orf10). A meta-analysis of all 331 C9orf72 carriers revealed that every A-allele of rs9357140 reduced hazard by 30% (P = 0.0002); and the median age of onset in AA-carriers was 6 years later than GG-carriers. In addition, we investigated a cohort of C9orf72 negative patients (n = 2634) affected by frontotemporal dementia and/or amyotrophic lateral sclerosis; and also found that the AA-genotype of rs9357140 was associated with a later age of onset (adjusted P = 0.007 for recessive model). Phenotype analyses detected significant association only in the largest subgroup of patients with frontotemporal dementia (n = 2142, adjusted P = 0.01 for recessive model). Gene expression studies of frontal cortex tissues from 25 autopsy cases affected by amyotrophic lateral sclerosis revealed that the G-allele of rs9357140 is associated with increased brain expression of LOC101929163 (a non-coding RNA) and HLA-DRB1 (involved in initiating immune responses), while the A-allele is associated with their reduced expression. Our findings suggest that carriers of the rs9357140 GG-genotype (linked to an earlier age of onset) might be more prone to be in a pro-inflammatory state (e.g. by microglia) than AA-carriers. Further, investigating the functional links within the C6orf10/LOC101929163/HLA-DRB1 pathway will be critical to better define age-dependent pathogenesis of frontotemporal dementia and amyotrophic lateral sclerosis.",
+ "publisher": "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie",
+ "issn": "1950-6007",
+ "date": "2016-09-16",
+ "abstract": "Huntington's disease (HD) is a progressive autosomal dominant disease, caused by a CAG repeat expansion in the HTT gene, resulting in an expanded polyglutamine stretch at the N-terminal of the huntingtin protein. An important event in HD pathogenesis appears to be the proteolysis of the mutant protein, which forms N-terminal huntingtin fragments. These fragments form insoluble aggregates and are found in nuclei and cytoplasm of affected neurons where they interfere with normal cell functioning. Important cleavage sites are encoded by exon 12 of HTT. A novel approach is Htt protein modification through exon skipping, which has recently been proven effective both in vitro and in vivo. Here we report proof-of-concept of AON 12.1 in vivo using the YAC128 mouse model of HD. Our results support and encourage future longitudinal studies exploring the therapeutic effects of sustained infusions in the YAC128 mouse model.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30252044"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27639545"
},
{
- "id": "pmid:30150298",
+ "id": "pmid:27540492",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/30150298",
- "title": "The",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27540492",
+ "title": "Effects of Anthocyanins on CAG Repeat Instability and Behaviour in Huntington's Disease R6/1 Mice.",
"type": "article-journal",
- "doi": "10.1128/mcb.00155-18",
+ "doi": "10.1371/currents.hd.58d04209ab6d5de0844db7ef5628ff67",
"authors": [
- ["Vitalay", "Fomin"],
- ["Patricia", "Richard"],
- ["Mainul", "Hoque"],
- ["Cynthia", "Li"],
- ["Zhuoying", "Gu"],
- ["Mercedes", "Fissore-O'Leary"],
- ["Bin", "Tian"],
- ["Carol", "Prives"],
- ["James L", "Manley"]
+ ["Linda", "M\u00f8llersen"],
+ ["Olve", "Moldestad"],
+ ["Alexander D", "Rowe"],
+ ["Anja", "Bj\u00f8lgerud"],
+ ["Ingunn", "Holm"],
+ ["Linda", "Tveter\u00e5s"],
+ ["Arne", "Klungland"],
+ ["Lars", "Retterst\u00f8l"]
],
- "publisher": "Molecular and cellular biology",
- "issn": "1098-5549",
- "date": "2018-10-29",
- "abstract": "A GGGGCC repeat expansion in the",
+ "publisher": "PLoS currents",
+ "issn": "2157-3999",
+ "date": "2016-07-05",
+ "abstract": "Huntington's disease (HD) is a progressive neurodegenerative disorder caused by CAG repeat expansions in the HTT gene. Somatic repeat expansion in the R6/1 mouse model of HD depends on mismatch repair and is worsened by base excision repair initiated by the 7,8-dihydroxy-8-oxoguanine-DNA glycosylase (Ogg1) or Nei-like 1 (Neil1). Ogg1 and Neil1 repairs common oxidative lesions.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30150298"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27540492"
},
{
- "id": "pmid:29973287",
+ "id": "pmid:27477323",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/29973287",
- "title": "Dipeptide repeat proteins activate a heat shock response found in C9ORF72-ALS/FTLD patients.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27477323",
+ "title": "Natural variation in sensory-motor white matter organization influences manifestations of Huntington's disease.",
"type": "article-journal",
- "doi": "10.1186/s40478-018-0555-8",
+ "doi": "10.1002/hbm.23332",
"authors": [
- ["Daniel A", "Mordes"],
- ["Mercedes", "Prudencio"],
- ["Lindsey D", "Goodman"],
- ["Joseph R", "Klim"],
- ["Rob", "Moccia"],
- ["Francesco", "Limone"],
- ["Olli", "Pietilainen"],
- ["Kaitavjeet", "Chowdhary"],
- ["Dennis W", "Dickson"],
- ["Rosa", "Rademakers"],
- ["Nancy M", "Bonini"],
- ["Leonard", "Petrucelli"],
- ["Kevin", "Eggan"]
+ ["Michael", "Orth"],
+ ["Sarah", "Gregory"],
+ ["Rachael I", "Scahill"],
+ ["Isabella Sm", "Mayer"],
+ ["Lora", "Minkova"],
+ ["Stefan", "Kl\u00f6ppel"],
+ ["Kiran K", "Seunarine"],
+ ["Lara", "Boyd"],
+ ["Beth", "Borowsky"],
+ ["Ralf", "Reilmann"],
+ ["G", "Bernhard Landwehrmeyer"],
+ ["Blair R", "Leavitt"],
+ ["Raymund Ac", "Roos"],
+ ["Alexandra", "Durr"],
+ ["Geraint", "Rees"],
+ ["John C", "Rothwell"],
+ ["Douglas", "Langbehn"],
+ ["Sarah J", "Tabrizi"]
],
- "publisher": "Acta neuropathologica communications",
- "issn": "2051-5960",
- "date": "2018-07-04",
- "abstract": "A hexanucleotide (GGGGCC) repeat expansion in C9ORF72 is the most common genetic contributor to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Reduced expression of the C9ORF72 gene product has been proposed as a potential contributor to disease pathogenesis. Additionally, repetitive RNAs and dipeptide repeat proteins (DPRs), such as poly-GR, can be produced by this hexanucleotide expansion that disrupt a number of cellular processes, potentially contributing to neural degeneration. To better discern which of these mechanisms leads to disease-associated changes in patient brains, we analyzed gene expression data generated from the cortex and cerebellum. We found that transcripts encoding heat shock proteins (HSPs) regulated by the HSF1 transcription factor were significantly induced in C9ORF72-ALS/FTLD patients relative to both sporadic ALS/FTLD cases and controls. Treatment of human neurons with chemically synthesized DPRs was sufficient to activate a similar transcriptional response. Expression of GGGGCC repeats and also poly-GR in the brains of Drosophila lead to the upregulation of HSF1 and the same highly-conserved HSPs. Additionally, HSF1 was a modifier of poly-GR toxicity in Drosophila. Our results suggest that the expression of DPRs are associated with upregulation of HSF1 and activation of a heat shock response in C9ORF72-ALS/FTLD.",
+ "publisher": "Human brain mapping",
+ "issn": "1097-0193",
+ "date": "2016-08-01",
+ "abstract": "While the HTT CAG-repeat expansion mutation causing Huntington's disease (HD) is highly correlated with the rate of pathogenesis leading to disease onset, considerable variance in age-at-onset remains unexplained. Therefore, other factors must influence the pathogenic process. We asked whether these factors were related to natural biological variation in the sensory-motor system. In 243 participants (96 premanifest and 35 manifest HD; 112 controls), sensory-motor structural MRI, tractography, resting-state fMRI, electrophysiology (including SEP amplitudes), motor score ratings, and grip force as sensory-motor performance were measured. Following individual modality analyses, we used principal component analysis (PCA) to identify patterns associated with sensory-motor performance, and manifest versus premanifest HD discrimination. We did not detect longitudinal differences over 12 months. PCA showed a pattern of loss of caudate, grey and white matter volume, cortical thickness in premotor and sensory cortex, and disturbed diffusivity in sensory-motor white matter tracts that was connected to CAG repeat length. Two further major principal components appeared in controls and HD individuals indicating that they represent natural biological variation unconnected to the HD mutation. One of these components did not influence HD while the other non-CAG-driven component of axial versus radial diffusivity contrast in white matter tracts were associated with sensory-motor performance and manifest HD. The first component reflects the expected CAG expansion effects on HD pathogenesis. One non-CAG-driven component reveals an independent influence on pathogenesis of biological variation in white matter tracts and merits further investigation to delineate the underlying mechanism and the potential it offers for disease modification. Hum Brain Mapp 37:4615-4628, 2016. \u00a9 2016 Wiley Periodicals, Inc.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29973287"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27477323"
},
{
- "id": "pmid:28192553",
+ "id": "pmid:27376585",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/28192553",
- "title": "Clinical Evidence of Disease Anticipation in Families Segregating a C9orf72 Repeat Expansion.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27376585",
+ "title": "Large-scale phenome analysis defines a behavioral signature for Huntington's disease genotype in mice.",
"type": "article-journal",
- "doi": "10.1001/jamaneurol.2016.4847",
+ "doi": "10.1038/nbt.3587",
"authors": [
- ["Sara", "Van Mossevelde"],
- ["Julie", "van der Zee"],
- ["Ilse", "Gijselinck"],
- ["Kristel", "Sleegers"],
- ["Jan", "De Bleecker"],
- ["Anne", "Sieben"],
- ["Rik", "Vandenberghe"],
- ["Tim", "Van Langenhove"],
- ["Jonathan", "Baets"],
- ["Olivier", "Deryck"],
- ["Patrick", "Santens"],
- ["Adrian", "Ivanoiu"],
- ["Christiana", "Willems"],
- ["Veerle", "B\u00e4umer"],
- ["Marleen", "Van den Broeck"],
- ["Karin", "Peeters"],
- ["Maria", "Mattheijssens"],
- ["Peter", "De Jonghe"],
- ["Patrick", "Cras"],
- ["Jean-Jacques", "Martin"],
- ["Marc", "Cruts"],
- ["Peter P", "De Deyn"],
- ["Sebastiaan", "Engelborghs"],
- ["Christine", "Van Broeckhoven"]
+ ["Vadim", "Alexandrov"],
+ ["Dani", "Brunner"],
+ ["Liliana B", "Menalled"],
+ ["Andrea", "Kudwa"],
+ ["Judy", "Watson-Johnson"],
+ ["Matthew", "Mazzella"],
+ ["Ian", "Russell"],
+ ["Melinda C", "Ruiz"],
+ ["Justin", "Torello"],
+ ["Emily", "Sabath"],
+ ["Ana", "Sanchez"],
+ ["Miguel", "Gomez"],
+ ["Igor", "Filipov"],
+ ["Kimberly", "Cox"],
+ ["Mei", "Kwan"],
+ ["Afshin", "Ghavami"],
+ ["Sylvie", "Ramboz"],
+ ["Brenda", "Lager"],
+ ["Vanessa C", "Wheeler"],
+ ["Jeff", "Aaronson"],
+ ["Jim", "Rosinski"],
+ ["James F", "Gusella"],
+ ["Marcy E", "MacDonald"],
+ ["David", "Howland"],
+ ["Seung", "Kwak"]
],
- "publisher": "JAMA neurology",
- "issn": "2168-6157",
- "date": "2017-04-01",
- "abstract": "Patients carrying a C9orf72 repeat expansion leading to frontotemporal dementia and/or amyotrophic lateral sclerosis have highly variable ages at onset of disease, suggesting the presence of modifying factors.",
+ "publisher": "Nature biotechnology",
+ "issn": "1546-1696",
+ "date": "2016-07-04",
+ "abstract": "Rapid technological advances for the frequent monitoring of health parameters have raised the intriguing possibility that an individual's genotype could be predicted from phenotypic data alone. Here we used a machine learning approach to analyze the phenotypic effects of polymorphic mutations in a mouse model of Huntington's disease that determine disease presentation and age of onset. The resulting model correlated variation across 3,086 behavioral traits with seven different CAG-repeat lengths in the huntingtin gene (Htt). We selected behavioral signatures for age and CAG-repeat length that most robustly distinguished between mouse lines and validated the model by correctly predicting the repeat length of a blinded mouse line. Sufficient discriminatory power to accurately predict genotype required combined analysis of >200 phenotypic features. Our results suggest that autosomal dominant disease-causing mutations could be predicted through the use of subtle behavioral signatures that emerge in large-scale, combinatorial analyses. Our work provides an open data platform that we now share with the research community to aid efforts focused on understanding the pathways that link behavioral consequences to genetic variation in Huntington's disease.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28192553"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27376585"
},
{
- "id": "pmid:27097283",
+ "id": "pmid:27335079",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/27097283",
- "title": "C9orf72 Hexanucleotide Expansions Are Associated with Altered Endoplasmic Reticulum Calcium Homeostasis and Stress Granule Formation in Induced Pluripotent Stem Cell-Derived Neurons from Patients with Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27335079",
+ "title": "Identification of Novel Microsatellite Markers <1 Mb from the HTT CAG Repeat and Development of a Single-Tube Tridecaplex PCR Panel of Highly Polymorphic Markers for Preimplantation Genetic Diagnosis of Huntington Disease.",
"type": "article-journal",
- "doi": "10.1002/stem.2388",
+ "doi": "10.1373/clinchem.2016.255711",
"authors": [
- ["Ruxandra", "Dafinca"],
- ["Jakub", "Scaber"],
- ["Nida'a", "Ababneh"],
- ["Tatjana", "Lalic"],
- ["Gregory", "Weir"],
- ["Helen", "Christian"],
- ["Jane", "Vowles"],
- ["Andrew G L", "Douglas"],
- ["Alexandra", "Fletcher-Jones"],
- ["Cathy", "Browne"],
- ["Mahito", "Nakanishi"],
- ["Martin R", "Turner"],
- ["Richard", "Wade-Martins"],
- ["Sally A", "Cowley"],
- ["Kevin", "Talbot"]
+ ["Mingjue", "Zhao"],
+ ["Min", "Chen"],
+ ["Caroline G", "Lee"],
+ ["Samuel S", "Chong"]
],
- "publisher": "Stem cells (Dayton, Ohio)",
- "issn": "1549-4918",
- "date": "2016-05-04",
- "abstract": "An expanded hexanucleotide repeat in a noncoding region of the C9orf72 gene is a major cause of amyotrophic lateral sclerosis (ALS), accounting for up to 40% of familial cases and 7% of sporadic ALS in European populations. We have generated induced pluripotent stem cells (iPSCs) from fibroblasts of patients carrying C9orf72 hexanucleotide expansions, differentiated these to functional motor and cortical neurons, and performed an extensive phenotypic characterization. In C9orf72 iPSC-derived motor neurons, decreased cell survival is correlated with dysfunction in Ca(2+) homeostasis, reduced levels of the antiapoptotic protein Bcl-2, increased endoplasmic reticulum (ER) stress, and reduced mitochondrial membrane potential. Furthermore, C9orf72 motor neurons, and also cortical neurons, show evidence of abnormal protein aggregation and stress granule formation. This study is an extensive characterization of iPSC-derived motor neurons as cellular models of ALS carrying C9orf72 hexanucleotide repeats, which describes a novel pathogenic link between C9orf72 mutations, dysregulation of calcium signaling, and altered proteostasis and provides a potential pharmacological target for the treatment of ALS and the related neurodegenerative disease frontotemporal dementia. Stem Cells 2016;34:2063-2078.",
+ "publisher": "Clinical chemistry",
+ "issn": "1530-8561",
+ "date": "2016-06-22",
+ "abstract": "Preimplantation genetic diagnosis (PGD) of Huntington disease (HD) generally employs linkage analysis of flanking microsatellite markers to complement direct mutation testing, as well as for exclusion testing. Thus far, only 10 linked markers have been developed for use in HD PGD, with a maximum of 3 markers coamplified successfully. We aimed to develop a single-tube multiplex PCR panel of highly polymorphic markers to simplify HD PGD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27097283"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27335079"
},
{
- "id": "pmid:22766072",
+ "id": "pmid:27271685",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/22766072",
- "title": "C9ORF72 repeat expansion in a large Italian ALS cohort: evidence of a founder effect.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27271685",
+ "title": "Folding Landscape of Mutant Huntingtin Exon1: Diffusible Multimers, Oligomers and Fibrils, and No Detectable Monomer.",
"type": "article-journal",
- "doi": "10.1016/j.neurobiolaging.2012.06.008",
+ "doi": "10.1371/journal.pone.0155747",
"authors": [
- ["Antonia", "Ratti"],
- ["Lucia", "Corrado"],
- ["Barbara", "Castellotti"],
- ["Roberto", "Del Bo"],
- ["Isabella", "Fogh"],
- ["Cristina", "Cereda"],
- ["Cinzia", "Tiloca"],
- ["Carla", "D'Ascenzo"],
- ["Alessandra", "Bagarotti"],
- ["Viviana", "Pensato"],
- ["Michela", "Ranieri"],
- ["Stella", "Gagliardi"],
- ["Daniela", "Calini"],
- ["Letizia", "Mazzini"],
- ["Franco", "Taroni"],
- ["Stefania", "Corti"],
- ["Mauro", "Ceroni"],
- ["Gaia D", "Oggioni"],
- ["Kuang", "Lin"],
- ["John F", "Powell"],
- ["Gianni", "Sorar\u00f9"],
- ["Nicola", "Ticozzi"],
- ["Giacomo P", "Comi"],
- ["Sandra", "D'Alfonso"],
- ["Cinzia", "Gellera"],
- ["Vincenzo", "Silani"]
+ ["Bankanidhi", "Sahoo"],
+ ["Irene", "Arduini"],
+ ["Kenneth W", "Drombosky"],
+ ["Ravindra", "Kodali"],
+ ["Laurie H", "Sanders"],
+ ["J Timothy", "Greenamyre"],
+ ["Ronald", "Wetzel"]
],
- "publisher": "Neurobiology of aging",
- "issn": "1558-1497",
- "date": "2012-07-04",
- "abstract": "A hexanucleotide repeat expansion (RE) in C9ORF72 gene was recently reported as the main cause of amyotrophic lateral sclerosis (ALS) and cases with frontotemporal dementia. We screened C9ORF72 in a large cohort of 259 familial ALS, 1275 sporadic ALS, and 862 control individuals of Italian descent. We found RE in 23.9% familial ALS, 5.1% sporadic ALS, and 0.2% controls. Two cases carried the RE together with mutations in other ALS-associated genes. The phenotype of RE carriers was characterized by bulbar-onset, shorter survival, and association with cognitive and behavioral impairment. Extrapyramidal and cerebellar signs were also observed in few patients. Genotype data revealed that 95% of RE carriers shared a restricted 10-single nucleotide polymorphism haplotype within the previously reported 20-single nucleotide polymorphism risk haplotype, detectable in only 27% of nonexpanded ALS cases and in 28% of controls, suggesting a common founder with cohorts of North European ancestry. Although C9ORF72 RE segregates with disease, the identification of RE both in controls and in patients carrying additional pathogenic mutations suggests that penetrance and phenotypic expression of C9ORF72 RE may depend on additional genetic risk factors.",
+ "publisher": "PloS one",
+ "issn": "1932-6203",
+ "date": "2016-06-06",
+ "abstract": "Expansion of the polyglutamine (polyQ) track of the Huntingtin (HTT) protein above 36 is associated with a sharply enhanced risk of Huntington's disease (HD). Although there is general agreement that HTT toxicity resides primarily in N-terminal fragments such as the HTT exon1 protein, there is no consensus on the nature of the physical states of HTT exon1 that are induced by polyQ expansion, nor on which of these states might be responsible for toxicity. One hypothesis is that polyQ expansion induces an alternative, toxic conformation in the HTT exon1 monomer. Alternative hypotheses posit that the toxic species is one of several possible aggregated states. Defining the nature of the toxic species is particularly challenging because of facile interconversion between physical states as well as challenges to identifying these states, especially in vivo. Here we describe the use of fluorescence correlation spectroscopy (FCS) to characterize the detailed time and repeat length dependent self-association of HTT exon1-like fragments both with chemically synthesized peptides in vitro and with cell-produced proteins in extracts and in living cells. We find that, in vitro, mutant HTT exon1 peptides engage in polyQ repeat length dependent dimer and tetramer formation, followed by time dependent formation of diffusible spherical and fibrillar oligomers and finally by larger, sedimentable amyloid fibrils. For expanded polyQ HTT exon1 expressed in PC12 cells, monomers are absent, with tetramers being the smallest molecular form detected, followed in the incubation time course by small, diffusible aggregates at 6-9 hours and larger, sedimentable aggregates that begin to build up at 12 hrs. In these cell cultures, significant nuclear DNA damage appears by 6 hours, followed at later times by caspase 3 induction, mitochondrial dysfunction, and cell death. Our data thus defines limits on the sizes and concentrations of different physical states of HTT exon1 along the reaction profile in the context of emerging cellular distress. The data provide some new candidates for the toxic species and some new reservations about more well-established candidates. Compared to other known markers of HTT toxicity, nuclear DNA damage appears to be a relatively early pathological event.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22766072"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27271685"
},
{
- "id": "pmid:21944779",
+ "id": "pmid:27221610",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21944779",
- "title": "A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27221610",
+ "title": "Altered Expression of the Long Noncoding RNA NEAT1 in Huntington's Disease.",
"type": "article-journal",
- "doi": "10.1016/j.neuron.2011.09.010",
+ "doi": "10.1007/s12035-016-9928-9",
"authors": [
- ["Alan E", "Renton"],
- ["Elisa", "Majounie"],
- ["Adrian", "Waite"],
- ["Javier", "Sim\u00f3n-S\u00e1nchez"],
- ["Sara", "Rollinson"],
- ["J Raphael", "Gibbs"],
- ["Jennifer C", "Schymick"],
- ["Hannu", "Laaksovirta"],
- ["John C", "van Swieten"],
- ["Liisa", "Myllykangas"],
- ["Hannu", "Kalimo"],
- ["Anders", "Paetau"],
- ["Yevgeniya", "Abramzon"],
- ["Anne M", "Remes"],
- ["Alice", "Kaganovich"],
- ["Sonja W", "Scholz"],
- ["Jamie", "Duckworth"],
- ["Jinhui", "Ding"],
- ["Daniel W", "Harmer"],
- ["Dena G", "Hernandez"],
- ["Janel O", "Johnson"],
- ["Kin", "Mok"],
- ["Mina", "Ryten"],
- ["Danyah", "Trabzuni"],
- ["Rita J", "Guerreiro"],
- ["Richard W", "Orrell"],
- ["James", "Neal"],
- ["Alex", "Murray"],
- ["Justin", "Pearson"],
- ["Iris E", "Jansen"],
- ["David", "Sondervan"],
- ["Harro", "Seelaar"],
- ["Derek", "Blake"],
- ["Kate", "Young"],
- ["Nicola", "Halliwell"],
- ["Janis Bennion", "Callister"],
- ["Greg", "Toulson"],
- ["Anna", "Richardson"],
- ["Alex", "Gerhard"],
- ["Julie", "Snowden"],
- ["David", "Mann"],
- ["David", "Neary"],
- ["Michael A", "Nalls"],
- ["Terhi", "Peuralinna"],
- ["Lilja", "Jansson"],
- ["Veli-Matti", "Isoviita"],
- ["Anna-Lotta", "Kaivorinne"],
- ["Maarit", "H\u00f6ltt\u00e4-Vuori"],
- ["Elina", "Ikonen"],
- ["Raimo", "Sulkava"],
- ["Michael", "Benatar"],
- ["Joanne", "Wuu"],
- ["Adriano", "Chi\u00f2"],
- ["Gabriella", "Restagno"],
- ["Giuseppe", "Borghero"],
- ["Mario", "Sabatelli"],
- ["David", "Heckerman"],
- ["Ekaterina", "Rogaeva"],
- ["Lorne", "Zinman"],
- ["Jeffrey D", "Rothstein"],
- ["Michael", "Sendtner"],
- ["Carsten", "Drepper"],
- ["Evan E", "Eichler"],
- ["Can", "Alkan"],
- ["Ziedulla", "Abdullaev"],
- ["Svetlana D", "Pack"],
- ["Amalia", "Dutra"],
- ["Evgenia", "Pak"],
- ["John", "Hardy"],
- ["Andrew", "Singleton"],
- ["Nigel M", "Williams"],
- ["Peter", "Heutink"],
- ["Stuart", "Pickering-Brown"],
- ["Huw R", "Morris"],
- ["Pentti J", "Tienari"],
- ["Bryan J", "Traynor"]
+ ["Jun-Sang", "Sunwoo"],
+ ["Soon-Tae", "Lee"],
+ ["Wooseok", "Im"],
+ ["Mijung", "Lee"],
+ ["Jung-Ick", "Byun"],
+ ["Keun-Hwa", "Jung"],
+ ["Kyung-Il", "Park"],
+ ["Ki-Young", "Jung"],
+ ["Sang Kun", "Lee"],
+ ["Kon", "Chu"],
+ ["Manho", "Kim"]
+ ],
+ "publisher": "Molecular neurobiology",
+ "issn": "1559-1182",
+ "date": "2016-05-25",
+ "abstract": "Huntington's disease (HD) is a devastating neurodegenerative disease caused by cytosine-adenine-guanine trinucleotide repeat expansion in the huntingtin gene. Growing evidence supports the regulatory functions of long noncoding RNAs (lncRNAs) in the disease process, but little is known about the association between lncRNAs and neuronal death in HD. Here, we evaluated the altered expression profiles of lncRNA in HD by using microarrays. Among dysregulated lncRNAs, we focused on the upregulation of nuclear paraspeckle assembly transcript 1 (NEAT1). Quantitative PCR analysis validated increased NEAT1 levels in the R6/2 mouse brain as well as the human HD postmortem brain. To determine the biological effects of NEAT1 on neuronal survival, neuro2A cells were transfected with the NEAT1 short isoform vector and were subjected to H",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27221610"
+},
+{
+ "id": "pmid:27182645",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27182645",
+ "title": "DNA Methylation Leads to DNA Repair Gene Down-Regulation and Trinucleotide Repeat Expansion in Patient-Derived Huntington Disease Cells.",
+ "type": "article-journal",
+ "doi": "10.1016/j.ajpath.2016.03.014",
+ "authors": [
+ ["Peter A", "Mollica"],
+ ["John A", "Reid"],
+ ["Roy C", "Ogle"],
+ ["Patrick C", "Sachs"],
+ ["Robert D", "Bruno"]
],
- "publisher": "Neuron",
- "issn": "1097-4199",
- "date": "2011-09-21",
- "abstract": "The chromosome 9p21 amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) locus contains one of the last major unidentified autosomal-dominant genes underlying these common neurodegenerative diseases. We have previously shown that a founder haplotype, covering the MOBKL2b, IFNK, and C9ORF72 genes, is present in the majority of cases linked to this region. Here we show that there is a large hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 on the affected haplotype. This repeat expansion segregates perfectly with disease in the Finnish population, underlying 46.0% of familial ALS and 21.1% of sporadic ALS in that population. Taken together with the D90A SOD1 mutation, 87% of familial ALS in Finland is now explained by a simple monogenic cause. The repeat expansion is also present in one-third of familial ALS cases of outbred European descent, making it the most common genetic cause of these fatal neurodegenerative diseases identified to date.",
+ "publisher": "The American journal of pathology",
+ "issn": "1525-2191",
+ "date": "2016-05-13",
+ "abstract": "Huntington disease (HD) is an autosomal dominantly inherited disease that exhibits genetic anticipation of affected progeny due to expansions of a trinucleotide repeat (TNR) region within the HTT gene. DNA repair machinery is a known effector of TNR instability; however, the specific defects in HD cells that lead to TNR expansion are unknown. We hypothesized that HD cells would be deficient in DNA repair gene expression. To test this hypothesis, we analyzed expression of select DNA repair genes involved in mismatch/loop-out repair (APEX1, BRCA1, RPA1, and RPA3) in patient-derived HD cells and found each was consistently down-regulated relative to wild-type samples taken from unaffected individuals in the same family. Rescue of DNA repair gene expression by 5-azacytidine treatment identified DNA methylation as a mediator of DNA repair gene expression deficiency. Bisulfite sequencing confirmed hypermethylation of the APEX1 promoter region in HD cells relative to control, as well as 5-azacytidine-induced hypomethylation. 5-Azacytidine treatments also resulted in stabilization of TNR expansion within the mutant HTT allele during long-term culture of HD cells. Our findings indicate that DNA methylation leads to DNA repair down-regulation and TNR instability in mitotically active HD cells and offer a proof of principle that epigenetic interventions can curb TNR expansions.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21944779"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27182645"
},
{
- "id": "pmid:9894797",
+ "id": "pmid:27031731",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/9894797",
- "title": "Carrier detection in Duchenne and Becker muscular dystrophy Argentine families.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27031731",
+ "title": "Delayed Onset and Reduced Cognitive Deficits through Pre-Conditioning with 3-Nitropropionic Acid is Dependent on Sex and CAG Repeat Length in the R6/2 Mouse Model of Huntington's Disease.",
"type": "article-journal",
- "doi": "10.1111/j.1399-0004.1998.tb03771.x",
+ "doi": "10.3233/jhd-160189",
"authors": [
- ["S E", "Baranzini"],
- ["F", "Giliberto"],
- ["V", "Dalamon"],
- ["C", "Barreiro"],
- ["M", "Garc\u00eda-Erro"],
- ["J", "Grippo"],
- ["I", "Szijan"]
+ ["Elizabeth A", "Skillings"],
+ ["A Jennifer", "Morton"]
],
- "publisher": "Clinical genetics",
- "issn": "0009-9163",
- "date": "1998-12-01",
- "abstract": "In order to offer carrier detection, genetic counseling, and prenatal diagnosis to families with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) in our country, segregation analysis of highly polymorphic short tandem repeats (STR) (dC-dA)n: (dG-dT)n loci was utilized. The risks to females of 15 DMD BMD families (9 familial and 6 sporadic) were evaluated on STR, pedigree and serum creatine kinase (SCK) data. From the 36 females at risk of being carriers (not including 8 obligate carriers), results of STR analysis were compatible with carrier status in 7 and not compatible in 20. In 9 females, no information regarding carriership was derived from the STR analysis. Prenatal diagnosis is now possible on the carrier females. Previously identified deletions in the central part of the gene were confirmed by STR analysis in 3 families. Five new alleles were identified in Argentine individuals; allele frequencies differed from those of North American people. Results derived from this study are useful for carrier detection and genetic counseling in DMD/BMD. One case of probable mosaicism in an unaffected father was detected on a pedigree basis in a family with DMD patients.",
+ "publisher": "Journal of Huntington's disease",
+ "issn": "1879-6400",
+ "date": "2016-01-01",
+ "abstract": "Impairments in energy metabolism are implicated in Huntington's disease (HD) pathogenesis. Reduced levels of the mitochondrial enzyme succinate dehydrogenase (SDH), the main element of complex II, are observed post mortem in the brains of HD patients, and energy metabolism defects have been identified in both presymptomatic and symptomatic HD patients.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9894797"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27031731"
},
{
- "id": "pmid:17877752",
+ "id": "pmid:27003665",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/17877752",
- "title": "DMPK-associated myotonic dystrophy and CTG repeats in Alabama African Americans.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27003665",
+ "title": "Does the Mutant CAG Expansion in Huntingtin mRNA Interfere with Exonucleolytic Cleavage of its First Exon?",
"type": "article-journal",
- "doi": "10.1111/j.1399-0004.2007.00883.x",
+ "doi": "10.3233/jhd-150183",
"authors": [
- ["R T", "Acton"],
- ["C A", "Rivers"],
- ["B", "Watson"],
- ["S J", "Oh"]
+ ["Wanzhao", "Liu"],
+ ["Edith L", "Pfister"],
+ ["Lori A", "Kennington"],
+ ["Kathryn O", "Chase"],
+ ["Christian", "Mueller"],
+ ["Marian", "DiFiglia"],
+ ["Neil", "Aronin"]
],
- "publisher": "Clinical genetics",
- "issn": "0009-9163",
- "date": "2007-09-17",
- "abstract": "Myotonic dystrophy type 1 (DM1) is a result of a CTG expansion in the 3'-untranslated region of the DMPK gene. DM1 is rare among African blacks who have fewer large CTG repeats in the normal range than other racial/ethnic groups. Neither the prevalence of DM1 nor the relationship of CTG expansion to clinical status in African Americans (AAs) is well documented. We describe two AA brothers with DM1, each of whom had CTG repeats of 5/639; their father was reported to have DM1 and had CTG repeats of 5/60. Other family members had CTG repeats of 5-14. An unrelated AA patient from a second kinship also had DM1; an analysis revealed CTG repeats of 27/191. In 161 Alabama AA control subjects, we observed 18 CTG alleles from 5 to 28 repeats; the most common allele had five CTG repeats. The frequency of CTG repeats >or=15 were greater (p < 0.0003) in Pygmy, Amhara Ethiopian, Ashkenazi Jewish, North African Jewish, Israeli Muslim Arab, European white, and Japanese populations than in the Alabama AA population. These data suggest that the risk for DM1 in AAs is intermediate between that of African blacks and whites of European descent.",
+ "publisher": "Journal of Huntington's disease",
+ "issn": "1879-6400",
+ "date": "2016-01-01",
+ "abstract": "Silencing mutant huntingtin mRNA by RNA interference (RNAi) is a therapeutic strategy for Huntington's disease. RNAi induces specific endonucleolytic cleavage of the target HTT mRNA, followed by exonucleolytic processing of the cleaved mRNA fragments.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17877752"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27003665"
},
{
- "id": "pmid:27708271",
+ "id": "pmid:26982737",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/27708271",
- "title": "Most Martin-Bell syndrome (FMR1-related disorder) Venezuelan patients did not show CGG expansion but instead display genetic heterogeneity.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26982737",
+ "title": "Genomic Instability Associated with p53 Knockdown in the Generation of Huntington's Disease Human Induced Pluripotent Stem Cells.",
"type": "article-journal",
- "doi": "10.1038/jhg.2016.114",
+ "doi": "10.1371/journal.pone.0150372",
"authors": [
- ["Yasser", "Vega"],
- ["Sergio", "Arias"],
- ["Irene", "Paradisi"]
+ ["Andrew M", "Tidball"],
+ ["M Diana", "Neely"],
+ ["Reed", "Chamberlin"],
+ ["Asad A", "Aboud"],
+ ["Kevin K", "Kumar"],
+ ["Bingying", "Han"],
+ ["Miles R", "Bryan"],
+ ["Michael", "Aschner"],
+ ["Kevin C", "Ess"],
+ ["Aaron B", "Bowman"]
],
- "publisher": "Journal of human genetics",
- "issn": "1435-232X",
- "date": "2016-10-06",
- "abstract": "Martin-Bell syndrome is mainly caused by the expansion of CGG trinucleotide repeats (>200 CGG) in the first exon of the FMR1 gene, leading to hypermethylation of the promoter region and silencing of the FMR1 protein expression. These changes are responsible for a phenotype with varying degrees of mental retardation, a long face with large and protruding ears, macroorchidism and autistic behavior. There may also be, however, patients who exhibit typical features of the syndrome without any expansion in the FMR1 gene; thus, other mechanisms affecting the expression of the FMR1 gene were assessed in 25 out of 29 ascertained patients with the typical phenotype without full mutation. Promoter methylation status of FMR1, mutations in its sequence and copy number variations (CNVs) in genes associated with intellectual disability were investigated. In 25 independent male patients without expansion, the promoter region was unmethylated; one patient with a full mutation showed methylation mosaicism; and a female patient had 81.2% of CpG sites methylated and 18.8% hemimethylated. One heterozygous duplication in exon 6 of the PDCD6 gene (programmed cell death 6) and a heterozygous deletion in exon 5 of the CHL1 gene (cell adhesion molecule L1), respectively, were found in two independent patients.",
+ "publisher": "PloS one",
+ "issn": "1932-6203",
+ "date": "2016-03-16",
+ "abstract": "Alterations in DNA damage response and repair have been observed in Huntington's disease (HD). We generated induced pluripotent stem cells (iPSC) from primary dermal fibroblasts of 5 patients with HD and 5 control subjects. A significant fraction of the HD iPSC lines had genomic abnormalities as assessed by karyotype analysis, while none of our control lines had detectable genomic abnormalities. We demonstrate a statistically significant increase in genomic instability in HD cells during reprogramming. We also report a significant association with repeat length and severity of this instability. Our karyotypically normal HD iPSCs also have elevated ATM-p53 signaling as shown by elevated levels of phosphorylated p53 and H2AX, indicating either elevated DNA damage or hypersensitive DNA damage signaling in HD iPSCs. Thus, increased DNA damage responses in the HD genotype is coincidental with the observed chromosomal aberrations. We conclude that the disease causing mutation in HD increases the propensity of chromosomal instability relative to control fibroblasts specifically during reprogramming to a pluripotent state by a commonly used episomal-based method that includes p53 knockdown.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27708271"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26982737"
},
{
- "id": "pmid:40084170",
+ "id": "pmid:26958025",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/40084170",
- "title": "A case report of oculopharyngodistal myopathy with 126 CGG repeat expansions in",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26958025",
+ "title": "Clinical and genetic data of Huntington disease in Moroccan patients.",
"type": "article-journal",
- "doi": "10.3389/fgene.2025.1472907",
+ "doi": "10.4314/ahs.v15i4.23",
"authors": [
- ["Wenjing", "Wang"],
- ["Tielun", "Yin"],
- ["Xinyu", "Zhang"],
- ["Zhaoxia", "Wang"],
- ["Tianyun", "Wang"],
- ["Shuo", "Zhang"],
- ["Yingshuang", "Zhang"],
- ["Dongsheng", "Fan"]
+ ["Ahmed", "Bouhouche"],
+ ["Wafaa", "Regragui"],
+ ["Hind", "Lamghari"],
+ ["Khadija", "Khaldi"],
+ ["Nazha", "Birouk"],
+ ["Safaa", "Lytim"],
+ ["Soufiane", "Bellamine"],
+ ["Yamna", "Kriouile"],
+ ["Naima", "Bouslam"],
+ ["El Hachmia Ait Ben", "Haddou"],
+ ["Mustapha Alaoui", "Faris"],
+ ["Ali", "Benomar"],
+ ["Mohamed", "Yahyaoui"]
],
- "publisher": "Frontiers in genetics",
- "issn": "1664-8021",
- "date": "2025-02-27",
- "abstract": "Oculopharyngodistal myopathy (OPDM) is a rare hereditary muscle disease characterized by progressive ptosis, ophthalmoplegia, dysphagia, dysarthria, and distal muscle weakness. The genetic basis was identified in 2019 with CGG repeat expansions in the noncoding region of",
+ "publisher": "African health sciences",
+ "issn": "1729-0503",
+ "date": "2015-12-01",
+ "abstract": "Huntington's disease (HD) occurs worldwide with prevalence varying from 0.1 to 10/100,000 depending of the ethnic origin. Since no data is available in the Maghreb population, the aim of this study is to describe clinical and genetic characteristics of Huntington patients of Moroccan origin.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40084170"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26958025"
},
{
- "id": "pmid:37716514",
+ "id": "pmid:26900923",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/37716514",
- "title": "Aberrant splicing of mutant huntingtin in Huntington's disease knock-in pigs.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26900923",
+ "title": "Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice.",
"type": "article-journal",
- "doi": "10.1016/j.nbd.2023.106291",
+ "doi": "10.1038/nn.4256",
"authors": [
- ["Huichun", "Tong"],
- ["Tianqi", "Yang"],
- ["Li", "Liu"],
- ["Caijuan", "Li"],
- ["Yize", "Sun"],
- ["Qingqing", "Jia"],
- ["Yiyang", "Qin"],
- ["Laiqiang", "Chen"],
- ["Xianxian", "Zhao"],
- ["Gongke", "Zhou"],
- ["Sen", "Yan"],
- ["Xiao-Jiang", "Li"],
- ["Shihua", "Li"]
+ ["Peter", "Langfelder"],
+ ["Jeffrey P", "Cantle"],
+ ["Doxa", "Chatzopoulou"],
+ ["Nan", "Wang"],
+ ["Fuying", "Gao"],
+ ["Ismael", "Al-Ramahi"],
+ ["Xiao-Hong", "Lu"],
+ ["Eliana Marisa", "Ramos"],
+ ["Karla", "El-Zein"],
+ ["Yining", "Zhao"],
+ ["Sandeep", "Deverasetty"],
+ ["Andreas", "Tebbe"],
+ ["Christoph", "Schaab"],
+ ["Daniel J", "Lavery"],
+ ["David", "Howland"],
+ ["Seung", "Kwak"],
+ ["Juan", "Botas"],
+ ["Jeffrey S", "Aaronson"],
+ ["Jim", "Rosinski"],
+ ["Giovanni", "Coppola"],
+ ["Steve", "Horvath"],
+ ["X William", "Yang"]
+ ],
+ "publisher": "Nature neuroscience",
+ "issn": "1546-1726",
+ "date": "2016-02-22",
+ "abstract": "To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington's disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat lengths. We found repeat length-dependent transcriptional signatures to be prominent in the striatum, less so in cortex, and minimal in the liver. Coexpression network analyses revealed 13 striatal and 5 cortical modules that correlated highly with CAG length and age, and that were preserved in HD models and sometimes in patients. Top striatal modules implicated mHtt CAG length and age in graded impairment in the expression of identity genes for striatal medium spiny neurons and in dysregulation of cyclic AMP signaling, cell death and protocadherin genes. We used proteomics to confirm 790 genes and 5 striatal modules with CAG length-dependent dysregulation at the protein level, and validated 22 striatal module genes as modifiers of mHtt toxicities in vivo.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26900923"
+},
+{
+ "id": "pmid:26849111",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26849111",
+ "title": "The HTT CAG-Expansion Mutation Determines Age at Death but Not Disease Duration in Huntington Disease.",
+ "type": "article-journal",
+ "doi": "10.1016/j.ajhg.2015.12.018",
+ "authors": [
+ ["Jae Whan", "Keum"],
+ ["Aram", "Shin"],
+ ["Tammy", "Gillis"],
+ ["Jayalakshmi Srinidhi", "Mysore"],
+ ["Kawther", "Abu Elneel"],
+ ["Diane", "Lucente"],
+ ["Tiffany", "Hadzi"],
+ ["Peter", "Holmans"],
+ ["Lesley", "Jones"],
+ ["Michael", "Orth"],
+ ["Seung", "Kwak"],
+ ["Marcy E", "MacDonald"],
+ ["James F", "Gusella"],
+ ["Jong-Min", "Lee"]
+ ],
+ "publisher": "American journal of human genetics",
+ "issn": "1537-6605",
+ "date": "2016-02-04",
+ "abstract": "Huntington disease (HD) is caused by an expanded HTT CAG repeat that leads in a length-dependent, completely dominant manner to onset of a characteristic movement disorder. HD also displays early mortality, so we tested whether the expanded CAG repeat exerts a dominant influence on age at death and on the duration of clinical disease. We found that, as with clinical onset, HD age at death is determined by expanded CAG-repeat length and has no contribution from the normal CAG allele. Surprisingly, disease duration is independent of the mutation's length. It is also unaffected by a strong genetic modifier of HD motor onset. These findings suggest two parsimonious alternatives. (1) HD pathogenesis is driven by mutant huntingtin, but before or near motor onset, sufficient CAG-driven damage occurs to permit CAG-independent processes and then lead to eventual death. In this scenario, some pathological changes and their clinical correlates could still worsen in a CAG-driven manner after disease onset, but these CAG-related progressive changes do not themselves determine duration. Alternatively, (2) HD pathogenesis is driven by mutant huntingtin acting in a CAG-dependent manner with different time courses in multiple cell types, and the cellular targets that lead to motor onset and death are different and independent. In this scenario, processes driven by HTT CAG length lead directly to death but not via the striatal pathology associated with motor manifestations. Each scenario has important ramifications for the design and testing of potential therapeutics, especially those aimed at preventing or delaying characteristic motor manifestations.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26849111"
+},
+{
+ "id": "pmid:26846325",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26846325",
+ "title": "Reduced Mitochondrial Function in Human Huntington Disease Lymphoblasts is Not Due to Alterations in Cardiolipin Metabolism or Mitochondrial Supercomplex Assembly.",
+ "type": "article-journal",
+ "doi": "10.1007/s11745-015-4110-0",
+ "authors": [
+ ["Edgard M", "Mejia"],
+ ["Sarah", "Chau"],
+ ["Genevieve C", "Sparagna"],
+ ["Simonetta", "Sipione"],
+ ["Grant M", "Hatch"]
+ ],
+ "publisher": "Lipids",
+ "issn": "1558-9307",
+ "date": "2016-02-04",
+ "abstract": "Huntington's Disease (HD) is an autosomal dominant disease that occurs as a result of expansion of the trinucleotide repeat CAG (glutamine) on the HTT gene. HD patients exhibit various forms of mitochondrial dysfunction within neurons and peripheral tissues. Cardiolipin (Ptd2Gro) is a polyglycerophospholipid found exclusively in mitochondria and is important for maintaining mitochondrial function. We examined if altered Ptd2Gro metabolism was involved in the mitochondrial dysfunction associated with HD. Mitochondrial basal respiration, spare respiratory capacity, ATP coupling efficiency and rate of glycolysis were markedly diminished in Epstein-Barr virus transformed HD lymphoblasts compared to controls (CTRL). Mitochondrial supercomplex formation and Complex I activity within these supercomplexes did not vary between HD patients with different length of CAG repeats and appeared unaltered compared to CTRL. In contrast, in vitro Complex I enzyme activity in mitochondrial enriched samples was reduced in HD lymphoblasts compared to CTRL. The total cellular pool size of Ptd2Gro and its synthesis/remodeling from [(3)H]acetate/[(14)C]oleate were unaltered in HD lymphoblasts compared to CTRL. In addition, the molecular species of Ptd2Gro were essentially unaltered in HD lymphoblasts compared to CTRL. We conclude that compared to CTRL lymphoblasts, HD lymphoblasts display impaired mitochondrial basal respiration, spare respiratory capacity, ATP coupling efficiency and rate of glycolysis with any pathological CAG repeat length, but this is not due to alterations in Ptd2Gro metabolism. We suggest that HD patient lymphoblasts may be a useful model to study defective energy metabolism that does not involve alterations in Ptd2Gro metabolism.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26846325"
+},
+{
+ "id": "pmid:26682993",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26682993",
+ "title": "Determinants of Onset of Huntington's Disease with Behavioral Symptoms: Insight from 92 Patients.",
+ "type": "article-journal",
+ "doi": "10.3233/jhd-150166",
+ "authors": [
+ ["Abhishek", "Lenka"],
+ ["Nitish L", "Kamble"],
+ ["V", "Sowmya"],
+ ["Ketan", "Jhunjhunwala"],
+ ["Ravi", "Yadav"],
+ ["M", "Netravathi"],
+ ["Mahesh", "Kandasamy"],
+ ["Nagaraj S", "Moily"],
+ ["Meera", "Purushottam"],
+ ["Sanjeev", "Jain"],
+ ["Pramod Kumar", "Pal"]
],
- "publisher": "Neurobiology of disease",
- "issn": "1095-953X",
- "date": "2023-09-15",
- "abstract": "Huntington's disease (HD) is an autosomal-dominant inherited neurodegenerative disease caused by a CAG repeat expansion in exon1 of the huntingtin gene (HTT). This expansion leads to the production of N-terminal mutant huntingtin protein (mHtt) that contains an expanded polyglutamine tract, which is toxic to neurons and causes neurodegeneration. While the production of N-terminal mHtt can be mediated by proteolytic cleavage of full-length mHtt, abnormal splicing of exon1-intron1 of mHtt has also been identified in the brains of HD mice and patients. However, the proportion of aberrantly spliced exon1 mHTT in relation to normal mHTT exon remains to be defined. In this study, HTT exon1 production was examined in the HD knock-in (KI) pig model, which more closely recapitulates neuropathology seen in HD patient brains than HD mouse models. The study revealed that aberrant spliced HTT exon1 is also present in the brains of HD pigs, but it is expressed at a much lower level than the normally spliced HTT exon products. These findings suggest that careful consideration is needed when assessing the contribution of aberrantly spliced mHTT exon1 to HD pathogenesis, and further rigorous investigation is required.",
+ "publisher": "Journal of Huntington's disease",
+ "issn": "1879-6400",
+ "date": "2015-01-01",
+ "abstract": "Huntington's disease (HD) is a genetically mediated neurodegenerative disorder characterized by presence of involuntary movements, behavioral problems and cognitive dysfunctions. Though few patients with HD may have behavioral symptoms at onset of the disease, studies comparing patients with behavioral symptoms at the onset of HD with those having motor symptoms are sparse.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37716514"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26682993"
},
{
- "id": "pmid:35395816",
+ "id": "pmid:26621114",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/35395816",
- "title": "Tissue-specific and repeat length-dependent somatic instability of the X-linked dystonia parkinsonism-associated CCCTCT repeat.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26621114",
+ "title": "Differential changes in thalamic and cortical excitatory synapses onto striatal spiny projection neurons in a Huntington disease mouse model.",
"type": "article-journal",
- "doi": "10.1186/s40478-022-01349-0",
+ "doi": "10.1016/j.nbd.2015.11.020",
"authors": [
- ["Lindsey N", "Campion"],
- ["Alan", "Mejia Maza"],
- ["Rachita", "Yadav"],
- ["Ellen B", "Penney"],
- ["Micaela G", "Murcar"],
- ["Kevin", "Correia"],
- ["Tammy", "Gillis"],
- ["Cara", "Fernandez-Cerado"],
- ["M Salvie", "Velasco-Andrada"],
- ["G Paul", "Legarda"],
- ["Niecy G", "Ganza-Bautista"],
- ["J Benedict B", "Lagarde"],
- ["Patrick J", "Acu\u00f1a"],
- ["Trisha", "Multhaupt-Buell"],
- ["Gabrielle", "Aldykiewicz"],
- ["Melanie L", "Supnet"],
- ["Jan K", "De Guzman"],
- ["Criscely", "Go"],
- ["Nutan", "Sharma"],
- ["Edwin L", "Munoz"],
- ["Mark C", "Ang"],
- ["Cid Czarina E", "Diesta"],
- ["D Cristopher", "Bragg"],
- ["Laurie J", "Ozelius"],
- ["Vanessa C", "Wheeler"]
+ ["Karolina", "Kolodziejczyk"],
+ ["Lynn A", "Raymond"]
],
- "publisher": "Acta neuropathologica communications",
- "issn": "2051-5960",
- "date": "2022-04-08",
- "abstract": "X-linked dystonia-parkinsonism (XDP) is a progressive adult-onset neurodegenerative disorder caused by insertion of a SINE-VNTR-Alu (SVA) retrotransposon in the TAF1 gene. The SVA retrotransposon contains a CCCTCT hexameric repeat tract of variable length, whose length is inversely correlated with age at onset. This places XDP in a broader class of repeat expansion diseases, characterized by the instability of their causative repeat mutations. Here, we observe similar inverse correlations between CCCTCT repeat length with age at onset and age at death and no obvious correlation with disease duration. To gain insight into repeat instability in XDP we performed comprehensive quantitative analyses of somatic instability of the XDP CCCTCT repeat in blood and in seventeen brain regions from affected males. Our findings reveal repeat length-dependent and expansion-based instability of the XDP CCCTCT repeat, with greater levels of expansion in brain than in blood. The brain exhibits regional-specific patterns of instability that are broadly similar across individuals, with cerebellum exhibiting low instability and cortical regions exhibiting relatively high instability. The spectrum of somatic instability in the brain includes a high proportion of moderate repeat length changes of up to 5 repeats, as well as expansions of\u2009~\u200920-\u2009>\u2009100 repeats and contractions of\u2009~\u200920-40 repeats at lower frequencies. Comparison with HTT CAG repeat instability in postmortem Huntington's disease brains reveals similar brain region-specific profiles, indicating common trans-acting factors that contribute to the instability of both repeats. Analyses in XDP brains of expansion of a different SVA-associated CCCTCT located in the LIPG gene, and not known to be disease-associated, reveals repeat length-dependent expansion at overall lower levels relative to the XDP CCCTCT repeat, suggesting that expansion propensity may be modified by local chromatin structure. Together, the data support a role for repeat length-dependent somatic expansion in the process(es) driving the onset of XDP and prompt further investigation into repeat dynamics and the relationship to disease.",
+ "publisher": "Neurobiology of disease",
+ "issn": "1095-953X",
+ "date": "2015-11-24",
+ "abstract": "Huntington disease (HD), a neurodegenerative disorder caused by CAG repeat expansion in the gene encoding huntingtin, predominantly affects the striatum, especially the spiny projection neurons (SPN). The striatum receives excitatory input from cortex and thalamus, and the role of the former has been well-studied in HD. Here, we report that mutated huntingtin alters function of thalamostriatal connections. We used a novel thalamostriatal (T-S) coculture and an established corticostriatal (C-S) coculture, generated from YAC128 HD and WT (FVB/NJ background strain) mice, to investigate excitatory neurotransmission onto striatal SPN. SPN in T-S coculture from WT mice showed similar mini-excitatory postsynaptic current (mEPSC) frequency and amplitude as in C-S coculture; however, both the frequency and amplitude were significantly reduced in YAC128 T-S coculture. Further investigation in T-S coculture showed similar excitatory synapse density in WT and YAC128 SPN dendrites by immunostaining, suggesting changes in total dendritic length or probability of release as possible explanations for mEPSC frequency changes. Synaptic N-methyl-D-aspartate receptor (NMDAR) current was similar, but extrasynaptic current, associated with cell death signaling, was enhanced in YAC128 SPN in T-S coculture. Employing optical stimulation of cortical versus thalamic afferents and recording from striatal SPN in brain slice, we found increased glutamate release probability and reduced AMPAR/NMDAR current ratios in thalamostriatal synapses, most prominently in YAC128. Enhanced extrasynaptic NMDAR current in YAC128 SPN was apparent with both cortical and thalamic stimulation. We conclude that thalamic afferents to the striatum are affected early, prior to an overt HD phenotype; however, changes in NMDAR localization in SPN are independent of the source of glutamatergic input.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35395816"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26621114"
},
{
- "id": "pmid:35275350",
+ "id": "pmid:26557176",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/35275350",
- "title": "Investigation of the Influence of TBP CAG/CAA Repeats in Conjunction with HTT CAG Repeats on Huntington's Disease Age at Onset in a Brazilian Sample.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26557176",
+ "title": "Childhood-onset (Juvenile) Huntington's disease: A rare case report.",
"type": "article-journal",
- "doi": "10.1007/s12031-021-01938-z",
+ "doi": "10.4103/1817-1745.165709",
"authors": [
- ["Iane Dos Santos", "da Silva"],
- ["Thays Andrade", "Apolin\u00e1rio"],
- ["Luciana", "de Andrade Agostinho"],
- ["Carmen Lucia Ant\u00e3o", "Paiva"]
+ ["Kailash Chandra", "Patra"],
+ ["Mukund Sudhir", "Shirolkar"]
],
- "publisher": "Journal of molecular neuroscience : MN",
- "issn": "1559-1166",
- "date": "2022-03-11",
- "abstract": "Huntington's disease (HD) is a genetic neurodegenerative progressive and fatal disease characterized by motor disorder, cognitive impairment, and behavioral problems, caused by expanded repeats of CAG trinucleotides in the HTT gene. The aim of this study was to investigate the influence of TBP gene CAG/CAA repeats in conjunction with HTT gene CAG repeats, on the age at HD onset in Brazilian individuals. Individuals diagnosed as molecularly negative for HD presented 29-39 TBP CAG/CAA. Their most frequent allele had 36 repeats. In individuals diagnosed as molecularly positive for HD, a range of 25-40 TBP CAG/ CAA was found. The most frequent TBP allele had 38 repeats. We also conducted TBP direct Sanger sequencing of some samples which demonstrated other four TBP structures different from the basic TBP structure and others reported in the literature. The HTT expanded CAG and TBP CAG/CAA repeat sizes jointly explained 66% of the age at onset (AO) in our HD patients. The strongest variable in the model associated with AO was the number of expanded HTT CAG repeats. The difference between the association of HD AO with HTT expanded CAG together with TBP CAG/CAA and the association of HD AO with HTT expanded CAG was 0.001 (\u2206R",
+ "publisher": "Journal of pediatric neurosciences",
+ "issn": "1817-1745",
+ "date": "2015-01-01",
+ "abstract": "Huntington's disease (HD) is a rare dominantly inherited neurodegenerative disorder characterized clinically by a combination of abnormal involuntary (choreic) movements, neuropsychiatric manifestations, and dementia. It is caused by an unstable CAG repeat expansion in the gene IT15 which encodes a Huntingtin protein. We present a case of a 9 year old boy who had developmental regression starting from the age of 8 years of age along with resistant seizures and signs of cerebellar involvement with absence of chorea and is on anticonvulsants, baclofen, and tetrabenzine. As is expected in a case of childhood-onset HD, our patient is rapidly deteriorating and is currently in the terminal phase of his illness along with resistant convulsions.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35275350"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26557176"
},
{
- "id": "pmid:35058188",
+ "id": "pmid:26439718",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/35058188",
- "title": "Time-resolved FRET screening identifies small molecular modifiers of mutant Huntingtin conformational inflexibility in patient-derived cells.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26439718",
+ "title": "Huntington Disease: Molecular Diagnostics Approach.",
"type": "article-journal",
- "doi": "10.1016/j.slasd.2021.10.005",
+ "doi": "10.1002/0471142905.hg0926s87",
"authors": [
- ["Johannes H", "Wilbertz"],
- ["Julia", "Frappier"],
- ["Sandra", "Muller"],
- ["Sabine", "Gratzer"],
- ["Walter", "Englaro"],
- ["Lisa M", "Stanek"],
- ["Barbara", "Calamini"]
+ ["Murat", "Bastepe"],
+ ["Winnie", "Xin"]
],
- "publisher": "SLAS discovery : advancing life sciences R & D",
- "issn": "2472-5560",
- "date": "2021-10-10",
- "abstract": "Huntington's disease (HD) is the most common monogenic neurodegenerative disease and is fatal. CAG repeat expansions in mutant Huntingtin (mHTT) exon 1\u00a0encode for polyglutamine (polyQ) stretches and influence age of onset and disease severity, depending on their length. mHTT is more structured compared to wild-type (wt) HTT, resulting in a decreased N-terminal conformational flexibility. mHTT inflexibility may contribute to both gain of function toxicity, due to increased mHTT aggregation propensity, but also to loss of function phenotypes, due to decreased interactions with binding partners. High-throughput-screening techniques to identify mHTT flexibility states and potential flexibility modifying small molecules are currently lacking. Here, we propose a novel approach for identifying small molecules that restore mHTT's conformational flexibility in human patient fibroblasts. We have applied a well-established antibody-based time-resolved F\u00f6rster resonance energy transfer (TR-FRET) immunoassay, which measures endogenous HTT flexibility using two validated HTT-specific antibodies, to a high-throughput screening platform. By performing a small-scale compound screen, we identified several small molecules that can partially rescue mHTT inflexibility, presumably by altering HTT post-translational modifications. Thus, we demonstrated that the HTT TR-FRET immunoassay can be miniaturized and applied to a compound screening workflow in patient cells. This automated assay can now be used in large screening campaigns to identify previously unknown HD drugs and drug targets.",
+ "publisher": "Current protocols in human genetics",
+ "issn": "1934-8258",
+ "date": "2015-10-06",
+ "abstract": "Huntington disease (HD) is caused by expansion of a CAG trinucleotide repeat in the first exon of the Huntingtin (HTT) gene. Molecular testing of Huntington disease for diagnostic confirmation and disease prediction requires detection of the CAG repeat expansion. There are three main types of HD genetic testing: (1) diagnostic testing to confirm or rule out disease, (2) presymptomatic testing to determine whether an at-risk individual inherited the expanded allele, and (3) prenatal testing to determine whether the fetus has inherited the expanded allele. This unit includes protocols that describe the complementary use of polymerase chain reactions (PCR) and Southern blot hybridization to accurately measure the CAG trinucleotide repeat size and interpret the test results. In addition, an indirect linkage analysis that does not reveal the unwanted parental HD status in a prenatal testing will also be discussed.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35058188"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26439718"
},
{
- "id": "pmid:34880419",
+ "id": "pmid:26397897",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/34880419",
- "title": "Huntingtin structure is orchestrated by HAP40 and shows a polyglutamine expansion-specific interaction with exon 1.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26397897",
+ "title": "Huntingtin Exists as Multiple Splice Forms in Human Brain.",
"type": "article-journal",
- "doi": "10.1038/s42003-021-02895-4",
+ "doi": "10.3233/jhd-150151",
"authors": [
- ["Rachel J", "Harding"],
- ["Justin C", "Deme"],
- ["Johannes F", "Hevler"],
- ["Sem", "Tamara"],
- ["Alexander", "Lemak"],
- ["Jeffrey P", "Cantle"],
- ["Magdalena M", "Szewczyk"],
- ["Nola", "Begeja"],
- ["Siobhan", "Goss"],
- ["Xiaobing", "Zuo"],
- ["Peter", "Loppnau"],
- ["Alma", "Seitova"],
- ["Ashley", "Hutchinson"],
- ["Lixin", "Fan"],
- ["Ray", "Truant"],
- ["Matthieu", "Schapira"],
- ["Jeffrey B", "Carroll"],
- ["Albert J R", "Heck"],
- ["Susan M", "Lea"],
- ["Cheryl H", "Arrowsmith"]
+ ["Matthew", "Mort"],
+ ["Francesca A", "Carlisle"],
+ ["Adrian J", "Waite"],
+ ["Lyn", "Elliston"],
+ ["Nicholas D", "Allen"],
+ ["Lesley", "Jones"],
+ ["Alis C", "Hughes"]
],
- "publisher": "Communications biology",
- "issn": "2399-3642",
- "date": "2021-12-08",
- "abstract": "Huntington's disease results from expansion of a glutamine-coding CAG tract in the huntingtin (HTT) gene, producing an aberrantly functioning form of HTT. Both wildtype and disease-state HTT form a hetero-dimer with HAP40 of unknown functional relevance. We demonstrate in vivo and in cell models that HTT and HAP40 cellular abundance are coupled. Integrating data from a 2.6\u2009\u00c5 cryo-electron microscopy structure, cross-linking mass spectrometry, small-angle X-ray scattering, and modeling, we provide a near-atomic-level view of HTT, its molecular interaction surfaces and compacted domain architecture, orchestrated by HAP40. Native mass\u00a0spectrometry reveals a remarkably stable hetero-dimer, potentially explaining the cellular inter-dependence of HTT and HAP40. The exon 1 region of HTT is dynamic but shows greater conformational variety in the polyglutamine expanded mutant than wildtype exon 1. Our data provide a foundation for future functional and drug discovery studies targeting Huntington's disease and illuminate the structural consequences of HTT polyglutamine expansion.",
+ "publisher": "Journal of Huntington's disease",
+ "issn": "1879-6400",
+ "date": "2015-01-01",
+ "abstract": "A CAG repeat expansion in HTT has been known to cause Huntington's disease for over 20 years. The genomic sequence of the 67 exon HTT is clear but few reports have detailed alternative splicing or alternative transcripts. Most eukaryotic genes with multiple exons show alternative splicing that increases the diversity of the transcriptome and proteome: it would be surprising if a gene with 67 known exons in its two major transcripts did not present some alternative transcripts.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34880419"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26397897"
},
{
- "id": "pmid:34663519",
+ "id": "pmid:26397895",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/34663519",
- "title": "Reduced mitochondrial complex II activity enhances cell death via intracellular reactive oxygen species in STHdhQ111 striatal neurons with mutant huntingtin.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26397895",
+ "title": "Is There Convincing Evidence that Intermediate Repeats in the HTT Gene Cause Huntington's Disease?",
"type": "article-journal",
- "doi": "10.1016/j.jphs.2021.09.001",
+ "doi": "10.3233/jhd-140120",
"authors": [
- ["Noria", "Okada"],
- ["Tomohiro", "Yako"],
- ["Shinsuke", "Nakamura"],
- ["Masamitsu", "Shimazawa"],
- ["Hideaki", "Hara"]
+ ["Mayke", "Oosterloo"],
+ ["Martine J", "Van Belzen"],
+ ["Emilia K", "Bijlsma"],
+ ["Raymund A C", "Roos"]
],
- "publisher": "Journal of pharmacological sciences",
- "issn": "1347-8648",
- "date": "2021-09-11",
- "abstract": "Huntington's disease (HD) is an inherited neurodegenerative disorder caused by CAG repeat expansion in the huntingtin (HTT) gene. Here, we examined the effects of antioxidants on 3-nitropropionic acid (3-NP; a mitochondrial complex II inhibitor)-induced mitochondrial dysfunction and cell death in STHdhQ111 striatal cells carrying homozygous mutant HTT with extended CAG repeats compared with those in STHdhQ7 striatal cells. 3-NP reduced cell viability and increased cell death both in STHdhQ111 and STHdhQ7, and the cytotoxicity was markedly attenuated by antioxidants (N-acetyl-l-cysteine and edaravone). Furthermore, 3-NP increased intracellular reactive oxygen species (ROS) production in both cell lines, and this increase was inhibited by antioxidants. Mitochondrial ROS was also increased by 3-NP in STHdhQ111 but not in STHdhQ7, and this increase was significantly inhibited by edaravone. Mitochondrial membrane potential (MMP) was lower in STHdhQ111 than that in STHdhQ7, and antioxidants prevented 3-NP-induced MMP decrease in STHdhQ111.3-NP enhanced oligomerization of dynamin-related protein 1 (Drp1), a protein that promotes mitochondrial fission in both cells, and both antioxidants prevented the increase in oligomerization. These results suggest that reduced mitochondrial complex II activity enhances cell death via intracellular ROS production and Drp1 oligomerization in striatal cells with mutant HTT and antioxidants may reduce striatal cell death.",
+ "publisher": "Journal of Huntington's disease",
+ "issn": "1879-6400",
+ "date": "2015-01-01",
+ "abstract": "Huntington's disease (HD) is a neurodegenerative disease associated with a CAG repeat expansion in the Huntingtin (HTT) gene. A trinucleotide size between 27 and 35 is considered 'intermediate' and not to cause symptoms and signs of HD. There are articles claiming otherwise, however publishing only the cases that have a HD phenotype introduces a significant publication bias. Our objective is to determine if there is convincing evidence that intermediate repeats (IA) cause HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34663519"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26397895"
},
{
- "id": "pmid:34520257",
+ "id": "pmid:26375764",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/34520257",
- "title": "Oligonucleotides Targeting DNA Repeats Downregulate",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26375764",
+ "title": "Oncologic Phenotype of Peripheral Neuroblastic Tumors Associated With PHOX2B Non-Polyalanine Repeat Expansion Mutations.",
"type": "article-journal",
- "doi": "10.1089/nat.2021.0021",
+ "doi": "10.1002/pbc.25723",
"authors": [
- ["Tea", "Umek"],
- ["Thomas", "Olsson"],
- ["Olof", "Gissberg"],
- ["Osama", "Saher"],
- ["Eman M", "Zaghloul"],
- ["Karin E", "Lundin"],
- ["Jesper", "Wengel"],
- ["Eric", "Hanse"],
- ["Henrik", "Zetterberg"],
- ["Dzeneta", "Vizlin-Hodzic"],
- ["C I Edvard", "Smith"],
- ["Rula", "Zain"]
+ ["Solveig", "Heide"],
+ ["Julien", "Masliah-Planchon"],
+ ["Bertrand", "Isidor"],
+ ["Anne", "Guimier"],
+ ["Damien", "Bodet"],
+ ["Carole", "Coze"],
+ ["Anne", "Deville"],
+ ["Estelle", "Thebault"],
+ ["Corinne Jeanne", "Pasquier"],
+ ["Elisabeth", "Cassagnau"],
+ ["Gaelle", "Pierron"],
+ ["Nathalie", "Cl\u00e9ment"],
+ ["Gudrun", "Schleiermacher"],
+ ["Jeanne", "Amiel"],
+ ["Olivier", "Delattre"],
+ ["Michel", "Peuchmaur"],
+ ["Franck", "Bourdeaut"]
],
- "publisher": "Nucleic acid therapeutics",
- "issn": "2159-3345",
- "date": "2021-09-13",
- "abstract": "Huntington's disease (HD) is one of the most common, dominantly inherited neurodegenerative disorders. It affects the striatum, cerebral cortex, and other subcortical structures leading to involuntary movement abnormalities, emotional disturbances, and cognitive impairments. HD is caused by a CAG\u2022CTG trinucleotide-repeat expansion in exon 1 of the",
+ "publisher": "Pediatric blood & cancer",
+ "issn": "1545-5017",
+ "date": "2015-09-16",
+ "abstract": "Germline non-polyalanine repeat expansion mutations in PHOX2B (PHOX2B NPARM) predispose to peripheral neuroblastic tumors (PNT), frequently in association with other neurocristopathies: Hirschsprung disease (HSCR) or congenital central hypoventilation syndrome (CCHS). Although PHOX2B polyalanine repeat expansions predispose to a low incidence of benign PNTs, the oncologic phenotype associated with PHOX2B NPARM is still not known in detail.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34520257"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26375764"
},
{
- "id": "pmid:34366363",
+ "id": "pmid:26247199",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/34366363",
- "title": "Subdural Hematoma as a Serious Complication of Huntington's Disease: An Observational Study.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26247199",
+ "title": "Suppression of Somatic Expansion Delays the Onset of Pathophysiology in a Mouse Model of Huntington's Disease.",
"type": "article-journal",
- "doi": "10.3233/jhd-210478",
+ "doi": "10.1371/journal.pgen.1005267",
"authors": [
- ["Marie", "Davis"],
- ["Vicki", "Wheelock"],
- ["Lauren", "Talman"],
- ["Caitlin", "Latimer"],
- ["Brenda", "Vicars"],
- ["Anny", "Lin"],
- ["Suman", "Jayadev"],
- ["Thomas", "Bird"]
+ ["Helen", "Budworth"],
+ ["Faye R", "Harris"],
+ ["Paul", "Williams"],
+ ["Do Yup", "Lee"],
+ ["Amy", "Holt"],
+ ["Jens", "Pahnke"],
+ ["Bartosz", "Szczesny"],
+ ["Karina", "Acevedo-Torres"],
+ ["Sylvette", "Ayala-Pe\u00f1a"],
+ ["Cynthia T", "McMurray"]
],
- "publisher": "Journal of Huntington's disease",
- "issn": "1879-6400",
- "date": "2021-01-01",
- "abstract": "Persons with Huntington's disease (HD) are at increased risk for subdural hematomas (SDH) because of underlying brain atrophy and increased frequency of falls and head trauma. SDH can cause serious disability, but there is little information about the association of SDH with HD in the medical literature.",
+ "publisher": "PLoS genetics",
+ "issn": "1553-7404",
+ "date": "2015-08-06",
+ "abstract": "Huntington's Disease (HD) is caused by inheritance of a single disease-length allele harboring an expanded CAG repeat, which continues to expand in somatic tissues with age. The inherited disease allele expresses a toxic protein, and whether further somatic expansion adds to toxicity is unknown. We have created an HD mouse model that resolves the effects of the inherited and somatic expansions. We show here that suppressing somatic expansion substantially delays the onset of disease in littermates that inherit the same disease-length allele. Furthermore, a pharmacological inhibitor, XJB-5-131, inhibits the lengthening of the repeat tracks, and correlates with rescue of motor decline in these animals. The results provide evidence that pharmacological approaches to offset disease progression are possible.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34366363"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26247199"
},
{
- "id": "pmid:34093422",
+ "id": "pmid:26232222",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/34093422",
- "title": "Ranking the Predictive Power of Clinical and Biological Features Associated With Disease Progression in Huntington's Disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26232222",
+ "title": "Identification of Genetic Factors that Modify Clinical Onset of Huntington's Disease.",
"type": "article-journal",
- "doi": "10.3389/fneur.2021.678484",
- "authors": [
- ["Naghmeh", "Ghazaleh"],
- ["Richard", "Houghton"],
- ["Giuseppe", "Palermo"],
- ["Scott A", "Schobel"],
- ["Peter A", "Wijeratne"],
- ["Jeffrey D", "Long"]
- ],
- "publisher": "Frontiers in neurology",
- "issn": "1664-2295",
- "date": "2021-05-20",
- "abstract": "Huntington's disease (HD) is characterised by a triad of cognitive, behavioural, and motor symptoms which lead to functional decline and loss of independence. With potential disease-modifying therapies in development, there is interest in accurately measuring HD progression and characterising prognostic variables to improve efficiency of clinical trials. Using the large, prospective Enroll-HD cohort, we investigated the relative contribution and ranking of potential prognostic variables in patients with manifest HD. A random forest regression model was trained to predict change of clinical outcomes based on the variables, which were ranked based on their contribution to the prediction. The highest-ranked variables included novel predictors of progression-being accompanied at clinical visit, cognitive impairment, age at diagnosis and tetrabenazine or antipsychotics use-in addition to established predictors, cytosine adenine guanine (CAG) repeat length and CAG-age product. The novel prognostic variables improved the ability of the model to predict clinical outcomes and may be candidates for statistical control in HD clinical studies.",
+ "doi": "10.1016/j.cell.2015.07.003",
+ "authors": [],
+ "publisher": "Cell",
+ "issn": "1097-4172",
+ "date": "2015-07-30",
+ "abstract": "As a Mendelian neurodegenerative disorder, the genetic risk of Huntington's disease (HD) is conferred entirely by an HTT CAG repeat expansion whose length is the primary determinant of the rate of pathogenesis leading to disease onset. To investigate the pathogenic process that precedes disease, we used genome-wide association (GWA) analysis to identify loci harboring genetic variations that alter the age at neurological onset of HD. A chromosome 15 locus displays two independent effects that accelerate or delay onset by 6.1 years and 1.4 years, respectively, whereas a chromosome 8 locus hastens onset by 1.6 years. Association at MLH1 and pathway analysis of the full GWA results support a role for DNA handling and repair mechanisms in altering the course of HD. Our findings demonstrate that HD disease modification in humans occurs in nature and offer a genetic route to identifying in-human validated therapeutic targets in this and other Mendelian disorders.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34093422"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26232222"
},
{
- "id": "pmid:33949657",
+ "id": "pmid:26218986",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/33949657",
- "title": "Lack of association of somatic CAG repeat expansion with striatal neurodegeneration in HD knock-in animal models.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26218986",
+ "title": "Nuclear retention of full-length HTT RNA is mediated by splicing factors MBNL1 and U2AF65.",
"type": "article-journal",
- "doi": "10.1093/hmg/ddab129",
+ "doi": "10.1038/srep12521",
"authors": [
- ["Dazhang", "Bai"],
- ["Peng", "Yin"],
- ["Yiran", "Zhang"],
- ["Fengwei", "Sun"],
- ["Laiqiang", "Chen"],
- ["Li", "Lin"],
- ["Sen", "Yan"],
- ["Shihua", "Li"],
- ["Xiao-Jiang", "Li"]
+ ["Xin", "Sun"],
+ ["Pan P", "Li"],
+ ["Shanshan", "Zhu"],
+ ["Rachael", "Cohen"],
+ ["Leonard O", "Marque"],
+ ["Christopher A", "Ross"],
+ ["Stefan M", "Pulst"],
+ ["Ho Yin Edwin", "Chan"],
+ ["Russell L", "Margolis"],
+ ["Dobrila D", "Rudnicki"]
],
- "publisher": "Human molecular genetics",
- "issn": "1460-2083",
- "date": "2021-07-28",
- "abstract": "Our previous work has established a huntingtin knock-in (KI) pig model that displays striatal neuronal loss, allowing us to examine if somatic CAG expansion in striatum accounts for the preferential neurodegeneration in Huntington disease (HD). We found that HD KI pigs do not display somatic CAG expansion in striatum as HD KI mice and that the majority of polyQ repeats in exon 1 HTT in the striatum of HD KI mice are fairly stable. We also found that striatal MSH2 and MLH3, which are involved in DNA repair, are more abundant in mouse brains than pig brains. Consistently inhibiting MSH2 and MLH3 reduced the somatic CAG expansion in HD KI mouse striatum with no influence on neuropathology. Our findings suggest that somatic CAG expansion is species-dependent, occurs in a small fraction of the HD gene in mice, and does not critically contribute to HD neuropathology.",
+ "publisher": "Scientific reports",
+ "issn": "2045-2322",
+ "date": "2015-07-28",
+ "abstract": "Huntington's disease (HD) is caused by a CAG repeat expansion in the huntingtin (HTT) gene. Recent evidence suggests that HD is a consequence of multimodal, non-mutually exclusive mechanisms of pathogenesis that involve both HTT protein- and HTT RNA-triggered mechanisms. Here we provide further evidence for the role of expanded HTT (expHTT) RNA in HD by demonstrating that a fragment of expHTT is cytotoxic in the absence of any translation and that the extent of cytotoxicity is similar to the cytotoxicity of an expHTT protein fragment encoded by a transcript of similar length and with a similar repeat size. In addition, full-length (FL) expHTT is retained in the nucleus. Overexpression of the splicing factor muscleblind-like 1 (MBNL1) increases nuclear retention of expHTT and decreases the expression of expHTT protein in the cytosol. The splicing and nuclear export factor U2AF65 has the opposite effect, decreasing expHTT nuclear retention and increasing expression of expHTT protein. This suggests that MBNL1 and U2AF65 play a role in nuclear export of expHTT RNA.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33949657"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26218986"
},
{
- "id": "pmid:33751106",
+ "id": "pmid:26148071",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/33751106",
- "title": "Somatic CAG expansion in Huntington's disease is dependent on the MLH3 endonuclease domain, which can be excluded via splice redirection.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26148071",
+ "title": "Exploring Genetic Factors Involved in Huntington Disease Age of Onset: E2F2 as a New Potential Modifier Gene.",
"type": "article-journal",
- "doi": "10.1093/nar/gkab152",
+ "doi": "10.1371/journal.pone.0131573",
"authors": [
- ["Jennie C L", "Roy"],
- ["Antonia", "Vitalo"],
- ["Marissa A", "Andrew"],
- ["Eduarda", "Mota-Silva"],
- ["Marina", "Kovalenko"],
- ["Zoe", "Burch"],
- ["Anh M", "Nhu"],
- ["Paula E", "Cohen"],
- ["Ed", "Grabczyk"],
- ["Vanessa C", "Wheeler"],
- ["Ricardo", "Mouro Pinto"]
+ ["Leire", "Valc\u00e1rcel-Ocete"],
+ ["Gorka", "Alkorta-Aranburu"],
+ ["Mikel", "Iriondo"],
+ ["Asier", "Fullaondo"],
+ ["Mar\u00eda", "Garc\u00eda-Barcina"],
+ ["Jos\u00e9 Manuel", "Fern\u00e1ndez-Garc\u00eda"],
+ ["Elena", "Lezcano-Garc\u00eda"],
+ ["Jos\u00e9 Mar\u00eda", "Losada-Domingo"],
+ ["Javier", "Ruiz-Ojeda"],
+ ["Amaia", "\u00c1lvarez de Arcaya"],
+ ["Jos\u00e9 Mar\u00eda", "P\u00e9rez-Ramos"],
+ ["Raymund A C", "Roos"],
+ ["J\u00f8rgen E", "Nielsen"],
+ ["Carsten", "Saft"],
+ ["Ana M", "Zubiaga"],
+ ["Ana", "Aguirre"]
],
- "publisher": "Nucleic acids research",
- "issn": "1362-4962",
- "date": "2021-04-19",
- "abstract": "Somatic expansion of the CAG repeat tract that causes Huntington's disease (HD) is thought to contribute to the rate of disease pathogenesis. Therefore, factors influencing repeat expansion are potential therapeutic targets. Genes in the DNA mismatch repair pathway are critical drivers of somatic expansion in HD mouse models. Here, we have tested, using genetic and pharmacological approaches, the role of the endonuclease domain of the mismatch repair protein MLH3 in somatic CAG expansion in HD mice and patient cells. A point mutation in the MLH3 endonuclease domain completely eliminated CAG expansion in the brain and peripheral tissues of a HD knock-in mouse model (HttQ111). To test whether the MLH3 endonuclease could be manipulated pharmacologically, we delivered splice switching oligonucleotides in mice to redirect Mlh3 splicing to exclude the endonuclease domain. Splice redirection to an isoform lacking the endonuclease domain was associated with reduced CAG expansion. Finally, CAG expansion in HD patient-derived primary fibroblasts was also significantly reduced by redirecting MLH3 splicing to the endogenous endonuclease domain-lacking isoform. These data indicate the potential of targeting the MLH3 endonuclease domain to slow somatic CAG repeat expansion in HD, a therapeutic strategy that may be applicable across multiple repeat expansion disorders.",
+ "publisher": "PloS one",
+ "issn": "1932-6203",
+ "date": "2015-07-06",
+ "abstract": "Age of onset (AO) of Huntington disease (HD) is mainly determined by the length of the CAG repeat expansion (CAGexp) in exon 1 of the HTT gene. Additional genetic variation has been suggested to contribute to AO, although the mechanism by which it could affect AO is presently unknown. The aim of this study is to explore the contribution of candidate genetic factors to HD AO in order to gain insight into the pathogenic mechanisms underlying this disorder. For that purpose, two AO definitions were used: the earliest age with unequivocal signs of HD (earliest AO or eAO), and the first motor symptoms age (motor AO or mAO). Multiple linear regression analyses were performed between genetic variation within 20 candidate genes and eAO or mAO, using DNA and clinical information of 253 HD patients from REGISTRY project. Gene expression analyses were carried out by RT-qPCR with an independent sample of 35 HD patients from Basque Country Hospitals. We found suggestive association signals between HD eAO and/or mAO and genetic variation within the E2F2, ATF7IP, GRIN2A, GRIN2B, LINC01559, HIP1 and GRIK2 genes. Among them, the most significant was the association between eAO and rs2742976, mapping to the promoter region of E2F2 transcription factor. Furthermore, rs2742976 T allele patient carriers exhibited significantly lower lymphocyte E2F2 gene expression, suggesting a possible implication of E2F2-dependent transcriptional activity in HD pathogenesis. Thus, E2F2 emerges as a new potential HD AO modifier factor.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33751106"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26148071"
},
{
- "id": "pmid:33611676",
+ "id": "pmid:26148061",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/33611676",
- "title": "CAG repeat instability in embryonic stem cells and derivative spermatogenic cells of transgenic Huntington's disease monkey.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26148061",
+ "title": "Structural Insights Reveal the Dynamics of the Repeating r(CAG) Transcript Found in Huntington's Disease (HD) and Spinocerebellar Ataxias (SCAs).",
"type": "article-journal",
- "doi": "10.1007/s10815-021-02106-3",
+ "doi": "10.1371/journal.pone.0131788",
"authors": [
- ["Sujittra", "Khampang"],
- ["Rangsun", "Parnpai"],
- ["Wiriya", "Mahikul"],
- ["Charles A", "Easley"],
- ["In Ki", "Cho"],
- ["Anthony W S", "Chan"]
+ ["Arpita", "Tawani"],
+ ["Amit", "Kumar"]
],
- "publisher": "Journal of assisted reproduction and genetics",
- "issn": "1573-7330",
- "date": "2021-02-20",
- "abstract": "The expansion of CAG (glutamine; Q) trinucleotide repeats (TNRs) predominantly occurs through male lineage in Huntington's disease (HD). As a result, offspring will have larger CAG repeats compared to their fathers, which causes an earlier onset of the disease called genetic anticipation. This study aims to develop a novel in vitro model to replicate CAG repeat instability in early spermatogenesis and demonstrate the biological process of genetic anticipation by using the HD stem cell model for the first time.",
+ "publisher": "PloS one",
+ "issn": "1932-6203",
+ "date": "2015-07-06",
+ "abstract": "In humans, neurodegenerative disorders such as Huntington's disease (HD) and many spinocerebellar ataxias (SCAs) have been found to be associated with CAG trinucleotide repeat expansion. An important RNA-mediated mechanism that causes these diseases involves the binding of the splicing regulator protein MBNL1 (Muscleblind-like 1 protein) to expanded r(CAG) repeats. Moreover, mutant huntingtin protein translated from expanded r(CAG) also yields toxic effects. To discern the role of mutant RNA in these diseases, it is essential to gather information about its structure. Detailed insight into the different structures and conformations adopted by these mutant transcripts is vital for developing therapeutics targeting them. Here, we report the crystal structure of an RNA model with a r(CAG) motif, which is complemented by an NMR-based solution structure obtained from restrained Molecular Dynamics (rMD) simulation studies. Crystal structure data of the RNA model resolved at 2.3 \u00c5 reveals non-canonical pairing of adenine in 5\u00b4-CAG/3\u00b4-GAC motif samples in different syn and anti conformations. The overall RNA structure has helical parameters intermediate to the A- and B-forms of nucleic acids due to the global widening of major grooves and base-pair preferences near internal AA loops. The comprehension of structural behaviour by studying the spectral features and the dynamics also supports the flexible nature of the r(CAG) motif.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33611676"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26148061"
},
{
- "id": "pmid:33547932",
+ "id": "pmid:26081309",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/33547932",
- "title": "Huntington's disease brain-derived small RNAs recapitulate associated neuropathology in mice.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26081309",
+ "title": "Psychiatric and cognitive symptoms in Huntington's disease are modified by polymorphisms in catecholamine regulating enzyme genes.",
"type": "article-journal",
- "doi": "10.1007/s00401-021-02272-9",
+ "doi": "10.1111/cge.12628",
"authors": [
- ["Jordi", "Creus-Muncunill"],
- ["Anna", "Guisado-Corcoll"],
- ["Veronica", "Venturi"],
- ["Lorena", "Pantano"],
- ["Georgia", "Escaram\u00eds"],
- ["Marta", "Garc\u00eda de Herreros"],
- ["Maria", "Solaguren-Beascoa"],
- ["Ana", "G\u00e1mez-Valero"],
- ["Cristina", "Navarrete"],
- ["Merc\u00e8", "Masana"],
- ["Franc", "Llorens"],
- ["Daniela", "Diaz-Lucena"],
- ["Esther", "P\u00e9rez-Navarro"],
- ["Eul\u00e0lia", "Mart\u00ed"]
+ ["T", "Vinther-Jensen"],
+ ["T T", "Nielsen"],
+ ["E", "Budtz-J\u00f8rgensen"],
+ ["I U", "Larsen"],
+ ["M M", "Hansen"],
+ ["L", "Hasholt"],
+ ["L E", "Hjermind"],
+ ["J E", "Nielsen"],
+ ["A", "N\u00f8rrem\u00f8lle"]
],
- "publisher": "Acta neuropathologica",
- "issn": "1432-0533",
- "date": "2021-02-06",
- "abstract": "Progressive motor alterations and selective death of striatal medium spiny neurons (MSNs) are key pathological hallmarks of Huntington's disease (HD), a neurodegenerative condition caused by a CAG trinucleotide repeat expansion in the coding region of the huntingtin (HTT) gene. Most research has focused on the pathogenic effects of the resultant protein product(s); however, growing evidence indicates that expanded CAG repeats within mutant HTT mRNA and derived small CAG repeat RNAs (sCAG) participate in HD pathophysiology. The individual contribution of protein versus RNA toxicity to HD pathophysiology remains largely uncharacterized and the role of other classes of small RNAs (sRNA) that are strongly perturbed in HD is uncertain. Here, we demonstrate that sRNA produced in the putamen of HD patients (HD-sRNA-PT) are sufficient to induce HD pathology in vivo. Mice injected with HD-sRNA-PT show motor abnormalities, decreased levels of striatal HD-related proteins, disruption of the indirect pathway, and strong transcriptional abnormalities, paralleling human HD pathology. Importantly, we show that the specific blockage of sCAG mitigates HD-sRNA-PT neurotoxicity only to a limited extent. This observation prompted us to identify other sRNA species enriched in HD putamen with neurotoxic potential. We detected high levels of tRNA fragments (tRFs) in HD putamen, and we validated the neurotoxic potential of an Alanine derived tRF in vitro. These results highlight that HD-sRNA-PT are neurotoxic, and suggest that multiple sRNA species contribute to striatal dysfunction and general transcriptomic changes, favoring therapeutic strategies based on the blockage of sRNA-mediated toxicity.",
+ "publisher": "Clinical genetics",
+ "issn": "1399-0004",
+ "date": "2015-07-17",
+ "abstract": "Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder characterized by motor, psychiatric, and cognitive manifestations. HD is caused by a CAG repeat expansion in the Huntingtin (HTT) gene but the exact pathogenesis remains unknown. Dopamine imbalance has previously been shown in HD, and furthermore dopamine is thought to be implicated in cognition, behavioral and motor disturbances. A substantiated inverse correlation between motor onset and the elongated CAG repeat in the HTT has been established. This relation does not account for the full variability of the motor onset, and efforts have been put into finding genetic modifiers of motor onset, however, mostly with unsuccessful outcome. In this study, we took an alternative approach focusing on symptom complexes and searched for modifiers of cognitive impairment and psychiatric symptoms in a well-described cohort of Danish HD gene-expansion carriers. We show that cognitive impairment and psychiatric symptoms in HD are modified by polymorphisms in the monoamine oxidase A (MAOA) and catechol-O-methyltransferase (COMT) genes and by the 4p16.3 B haplotype. These results support the theory of dopamine imbalance in HD, and point toward more personalized treatment modalities of HD in the future.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33547932"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26081309"
},
{
- "id": "pmid:33249136",
+ "id": "pmid:25990798",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/33249136",
- "title": "An integrated metagenomics and metabolomics approach implicates the microbiota-gut-brain axis in the pathogenesis of Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25990798",
+ "title": "Transfer of genetic therapy across human populations: molecular targets for increasing patient coverage in repeat expansion diseases.",
"type": "article-journal",
- "doi": "10.1016/j.nbd.2020.105199",
+ "doi": "10.1038/ejhg.2015.94",
"authors": [
- ["Geraldine", "Kong"],
- ["Susan", "Ellul"],
- ["Vinod K", "Narayana"],
- ["Komal", "Kanojia"],
- ["Harvey Tran Thai", "Ha"],
- ["Shanshan", "Li"],
- ["Thibault", "Renoir"],
- ["Kim-Anh L\u00ea", "Cao"],
- ["Anthony J", "Hannan"]
+ ["Miguel A", "Varela"],
+ ["Helen J", "Curtis"],
+ ["Andrew G L", "Douglas"],
+ ["Suzan M", "Hammond"],
+ ["Aisling J", "O'Loughlin"],
+ ["Maria J", "Sobrido"],
+ ["Janine", "Scholefield"],
+ ["Matthew J A", "Wood"]
],
- "publisher": "Neurobiology of disease",
- "issn": "1095-953X",
- "date": "2020-11-26",
- "abstract": "Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder with onset and severity of symptoms influenced by various environmental factors. Recent discoveries have highlighted the importance of the gastrointestinal microbiome in mediating the gut-brain-axis bidirectional communication via circulating factors. Using shotgun sequencing, we investigated the gut microbiome composition in the R6/1 transgenic mouse model of HD from 4 to 12\u00a0weeks of age (early adolescent through to adult stages). Targeted metabolomics was also performed on the blood plasma of these mice (n\u00a0=\u00a09 per group) at 12\u00a0weeks of age to investigate potential effects of gut dysbiosis on the plasma metabolome profile.",
+ "publisher": "European journal of human genetics : EJHG",
+ "issn": "1476-5438",
+ "date": "2015-05-20",
+ "abstract": "Allele-specific gene therapy aims to silence expression of mutant alleles through targeting of disease-linked single-nucleotide polymorphisms (SNPs). However, SNP linkage to disease varies between populations, making such molecular therapies applicable only to a subset of patients. Moreover, not all SNPs have the molecular features necessary for potent gene silencing. Here we provide knowledge to allow the maximisation of patient coverage by building a comprehensive understanding of SNPs ranked according to their predicted suitability toward allele-specific silencing in 14 repeat expansion diseases: amyotrophic lateral sclerosis and frontotemporal dementia, dentatorubral-pallidoluysian atrophy, myotonic dystrophy 1, myotonic dystrophy 2, Huntington's disease and several spinocerebellar ataxias. Our systematic analysis of DNA sequence variation shows that most annotated SNPs are not suitable for potent allele-specific silencing across populations because of suboptimal sequence features and low variability (>97% in HD). We suggest maximising patient coverage by selecting SNPs with high heterozygosity across populations, and preferentially targeting SNPs that lead to purine:purine mismatches in wild-type alleles to obtain potent allele-specific silencing. We therefore provide fundamental knowledge on strategies for optimising patient coverage of therapeutics for microsatellite expansion disorders by linking analysis of population genetic variation to the selection of molecular targets.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33249136"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25990798"
},
{
- "id": "pmid:32979842",
+ "id": "pmid:25972145",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/32979842",
- "title": "Structural brain correlates of dementia in Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25972145",
+ "title": "In Vitro Differentiation of Human Neural Progenitor Cells Into Striatal GABAergic Neurons.",
"type": "article-journal",
- "doi": "10.1016/j.nicl.2020.102415",
+ "doi": "10.5966/sctm.2014-0083",
"authors": [
- ["Saul", "Martinez-Horta"],
- ["Frederic", "Sampedro"],
- ["Andrea", "Horta-Barba"],
- ["Jes\u00fas", "Perez-Perez"],
- ["Javier", "Pagonabarraga"],
- ["Beatriz", "Gomez-Anson"],
- ["Jaime", "Kulisevsky"]
+ ["Lin", "Lin"],
+ ["Juan", "Yuan"],
+ ["Bjoern", "Sander"],
+ ["Monika M", "Golas"]
],
- "publisher": "NeuroImage. Clinical",
- "issn": "2213-1582",
- "date": "2020-09-09",
- "abstract": "Huntington's disease (HD) is a fatal genetic neurodegenerative disorder with no effective treatment currently available. Progressive basal ganglia and whole-brain atrophy and concurrent cognitive deterioration are prototypical aspects of HD. However, the specific patterns of brain atrophy underlying cognitive impairment of different severity in HD are poorly understood. The aim of this study was to investigate the specific structural brain correlates of major cognitive deficits in HD and to explore its association with neuropsychological indicators.",
+ "publisher": "Stem cells translational medicine",
+ "issn": "2157-6564",
+ "date": "2015-05-13",
+ "abstract": ": Huntington's disease (HD) results from a CAG repeat expansion in the gene encoding the huntingtin protein. This inherited disorder is characterized by progressive neurodegeneration. In particular, HD progression involves the loss of striatal projection neurons. The limited availability of reliable sources of human striatal projection neurons currently hampers our understanding of HD mechanisms and hinders the development of novel HD treatments. In this paper, we described two- and three-step methods for differentiating human neural progenitor cells toward striatal projection neurons. In the two-step differentiation protocol, 90%, 54%, and 6% of MAP2-positive cells were immunopositive for GABA, calbindin (CALB1), and DARPP-32/PPP1R1B, respectively. In the three-step differentiation protocol, 96%, 84%, and 21% of MAP2-positive cells were immunopositive for GABA, calbindin, and DARPP-32/PPP1R1B, respectively. In line with a striatal projection neuron phenotype, cells differentiated with our protocols displayed significantly increased expression of MAP2, CALB1, DARPP-32/PPP1R1B, ARPP21, and CTIP2. Application of glutamate receptor agonists induced calcium influx; accordingly, the cells also expressed various ionotropic glutamate receptor subunits. Differentiated cells also released GABA on stimulation. We suggest that our three-step differentiation protocol presents a reliable and simplified method for the generation of striatal projection neurons, yielding a critical resource for neuronal physiology and neurodegenerative disorder studies.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32979842"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25972145"
},
{
- "id": "pmid:32979507",
+ "id": "pmid:25934536",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/32979507",
- "title": "Inconsistencies in histone acetylation patterns among different HD model systems and HD post-mortem brains.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25934536",
+ "title": "Nocturnal agitation in Huntington disease is caused by arousal-related abnormal movements rather than by rapid eye movement sleep behavior disorder.",
"type": "article-journal",
- "doi": "10.1016/j.nbd.2020.105092",
+ "doi": "10.1016/j.sleep.2014.12.021",
"authors": [
- ["Pritika", "Narayan"],
- ["Suzanne", "Reid"],
- ["Emma L", "Scotter"],
- ["Ailsa L", "McGregor"],
- ["Nasim F", "Mehrabi"],
- ["Malvindar K", "Singh-Bains"],
- ["Michelle", "Glass"],
- ["Richard L M", "Faull"],
- ["Russell G", "Snell"],
- ["Mike", "Dragunow"]
+ ["Dulce", "Neutel"],
+ ["Maya", "Tchikviladz\u00e9"],
+ ["Perrine", "Charles"],
+ ["Smaranda", "Leu-Semenescu"],
+ ["Emmanuel", "Roze"],
+ ["Alexandra", "Durr"],
+ ["Isabelle", "Arnulf"]
],
- "publisher": "Neurobiology of disease",
- "issn": "1095-953X",
- "date": "2020-09-23",
- "abstract": "Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in exon 1 of the huntingtin gene. Emerging evidence shows that additional epigenetic factors can modify disease phenotypes. Harnessing the ability of the epigenome to modify the disease for therapeutic purposes is therefore of interest. Epigenome modifiers, such as histone deacetylase inhibitors (HDACi), have improved pathology in a range of HD models. Yet in clinical trials, HDACi have failed to alleviate HD symptoms in patients. This study investigated potential reasons for the lack of translation of the therapeutic benefits of HDACi from lab to clinic. We analysed histone acetylation patterns of immuno-positive nuclei from brain sections and tissue microarrays from post-mortem human control and HD cases alongside several well-established HD models (OVT73 transgenic HD sheep, YAC128 mice, and an in vitro cell model expressing 97Q mutant huntingtin). Significant increases in histone H4 acetylation were observed in post-mortem HD cases, OVT73 transgenic HD sheep and in vitro models; these changes were absent in YAC128 mice. In addition, nuclear labelling for acetyl-histone H4 levels were inversely proportional to mutant huntingtin aggregate load in HD human cortex. Our data raise concerns regarding the utility of HDACi for the treatment of HD when regions of pathology exhibit already elevated histone acetylation patterns and emphasize the importance of searching for alternative epigenetic targets in future therapeutic strategies aiming to rescue HD phenotypes.",
+ "publisher": "Sleep medicine",
+ "issn": "1878-5506",
+ "date": "2015-03-03",
+ "abstract": "Patients with Huntington disease (HD) and their spouses often complain of agitation during sleep, but the causes are mostly unknown.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32979507"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25934536"
},
{
- "id": "pmid:32825467",
+ "id": "pmid:25889241",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/32825467",
- "title": "The Association between CAG Repeat Length and Age of Onset of Juvenile-Onset Huntington's Disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25889241",
+ "title": "miR-10b-5p expression in Huntington's disease brain relates to age of onset and the extent of striatal involvement.",
"type": "article-journal",
- "doi": "10.3390/brainsci10090575",
+ "doi": "10.1186/s12920-015-0083-3",
"authors": [
- ["Jordan L", "Schultz"],
- ["Amelia D", "Moser"],
- ["Peg C", "Nopoulos"]
+ ["Andrew G", "Hoss"],
+ ["Adam", "Labadorf"],
+ ["Jeanne C", "Latourelle"],
+ ["Vinay K", "Kartha"],
+ ["Tiffany C", "Hadzi"],
+ ["James F", "Gusella"],
+ ["Marcy E", "MacDonald"],
+ ["Jiang-Fan", "Chen"],
+ ["Schahram", "Akbarian"],
+ ["Zhiping", "Weng"],
+ ["Jean Paul", "Vonsattel"],
+ ["Richard H", "Myers"]
],
- "publisher": "Brain sciences",
- "issn": "2076-3425",
- "date": "2020-08-20",
- "abstract": "There is a known negative association between cytosine-adenine-guanine (CAG) repeat length and the age of motor onset (AMO) in adult-onset Huntington's Disease (AOHD). This relationship is less clear in patients with juvenile-onset Huntington's disease (JOHD), however, given the rarity of this patient population. The aim of this study was to investigate this relationship amongst a relatively large group of patients with JOHD using data from the Kids-JOHD study. Additionally, we analyzed data from the Enroll-HD platform and the Predict-HD study to compare the relationship between CAG repeat length and AMO amongst patients with AOHD to that amongst patients with JOHD using linear regression models. In line with previous reports, the variance in AMO that was predicted by CAG repeat length was 59% (",
+ "publisher": "BMC medical genomics",
+ "issn": "1755-8794",
+ "date": "2015-03-01",
+ "abstract": "MicroRNAs (miRNAs) are small non-coding RNAs that recognize sites of complementarity of target messenger RNAs, resulting in transcriptional regulation and translational repression of target genes. In Huntington's disease (HD), a neurodegenerative disease caused by a trinucleotide repeat expansion, miRNA dyregulation has been reported, which may impact gene expression and modify the progression and severity of HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32825467"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25889241"
},
{
- "id": "pmid:32612964",
+ "id": "pmid:25876513",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/32612964",
- "title": "Polymorphisms of SLC19A1 80 G>A, MTHFR 677 C>T, and Tandem TS Repeats Influence Pharmacokinetics, Acute Liver Toxicity, and Vomiting in Children With Acute Lymphoblastic Leukemia Treated With High Doses of Methotrexate.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25876513",
+ "title": "RTP801 Is Involved in Mutant Huntingtin-Induced Cell Death.",
"type": "article-journal",
- "doi": "10.3389/fped.2020.00307",
+ "doi": "10.1007/s12035-015-9166-6",
"authors": [
- ["Magdalena", "Cwiklinska"],
- ["Malgorzata", "Czogala"],
- ["Kinga", "Kwiecinska"],
- ["Anna", "Madetko-Talowska"],
- ["Malgorzata", "Szafarz"],
- ["Katarzyna", "Pawinska"],
- ["Aleksandra", "Wieczorek"],
- ["Tomasz", "Klekawka"],
- ["Magdalena", "Rej"],
- ["Konrad", "Stepien"],
- ["Przemyslaw", "Halubiec"],
- ["Agnieszka", "Lazarczyk"],
- ["Karol", "Miklusiak"],
- ["Miroslaw", "Bik-Multanowski"],
- ["Walentyna", "Balwierz"],
- ["Szymon", "Skoczen"]
+ ["N\u00faria", "Mart\u00edn-Flores"],
+ ["Joan", "Roman\u00ed-Aumedes"],
+ ["Laura", "Ru\u00e9"],
+ ["Merc\u00e8", "Canal"],
+ ["Phil", "Sanders"],
+ ["Marco", "Straccia"],
+ ["Nicholas D", "Allen"],
+ ["Jordi", "Alberch"],
+ ["Josep M", "Canals"],
+ ["Esther", "P\u00e9rez-Navarro"],
+ ["Cristina", "Malagelada"]
],
- "publisher": "Frontiers in pediatrics",
- "issn": "2296-2360",
- "date": "2020-06-16",
- "abstract": "",
+ "publisher": "Molecular neurobiology",
+ "issn": "1559-1182",
+ "date": "2015-04-16",
+ "abstract": "RTP801 expression is induced by cellular stress and has a pro-apoptotic function in non-proliferating differentiated cells such as neurons. In several neurodegenerative disorders, including Parkinson's disease and Alzheimer's disease, elevated levels of RTP801 have been observed, which suggests a role for RTP801 in neuronal death. Neuronal death is also a pathological hallmark in Huntington's disease (HD), an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. Currently, the exact mechanisms underlying mutant huntingtin (mhtt)-induced toxicity are still unclear. Here, we investigated whether RTP801 is involved in (mhtt)-induced cell death. Ectopic exon-1 mhtt elevated RTP801 mRNA and protein levels in nerve growth factor (NGF)-differentiated PC12 cells and in rat primary cortical neurons. In neuronal PC12 cells, mhtt also contributed to RTP801 protein elevation by reducing its proteasomal degradation rate, in addition to promoting RTP801 gene expression. Interestingly, silencing RTP801 expression with short hairpin RNAs (shRNAs) blocked mhtt-induced cell death in NGF-differentiated PC12 cells. However, RTP801 protein levels were not altered in the striatum of Hdh(Q7/Q111) and R6/1 mice, two HD models that display motor deficits but not neuronal death. Importantly, RTP801 protein levels were elevated in both neural telencephalic progenitors differentiated from HD patient-derived induced pluripotent stem cells and in the putamen and cerebellum of human HD postmortem brains. Taken together, our results suggest that RTP801 is a novel downstream effector of mhtt-induced toxicity and that it may be relevant to the human disease.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32612964"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25876513"
},
{
- "id": "pmid:32424160",
+ "id": "pmid:25859666",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/32424160",
- "title": "Co-chaperones DNAJA1 and DNAJB6 are critical for regulation of polyglutamine aggregation.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25859666",
+ "title": "Characterization of HTT inclusion size, location, and timing in the zQ175 mouse model of Huntington's disease: an in vivo high-content imaging study.",
"type": "article-journal",
- "doi": "10.1038/s41598-020-65046-5",
+ "doi": "10.1371/journal.pone.0123527",
"authors": [
- ["Claudio", "Rodr\u00edguez-Gonz\u00e1lez"],
- ["Shiying", "Lin"],
- ["Sertan", "Arkan"],
- ["Christian", "Hansen"]
+ ["Nikisha", "Carty"],
+ ["Nad\u00e8ge", "Berson"],
+ ["Karsten", "Tillack"],
+ ["Christina", "Thiede"],
+ ["Diana", "Scholz"],
+ ["Karsten", "Kottig"],
+ ["Yalda", "Sedaghat"],
+ ["Christina", "Gabrysiak"],
+ ["George", "Yohrling"],
+ ["Heinz", "von der Kammer"],
+ ["Andreas", "Ebneth"],
+ ["Volker", "Mack"],
+ ["Ignacio", "Munoz-Sanjuan"],
+ ["Seung", "Kwak"]
],
- "publisher": "Scientific reports",
- "issn": "2045-2322",
- "date": "2020-05-18",
- "abstract": "Huntington's disease (HD) is caused by CAG repeat expansion in the huntingtin gene. The expanded polyglutamine (polyQ) repeat of the encoded protein leads to protein misfolding and aggregation, resulting in increased neuronal cell death. DNAJ co-chaperones play a crucial role in transferring misfolded/unfolded proteins to HSP70 chaperones, which play an essential role for protein folding. Here, we investigated the effect of knock out (KO) of three individual DNAJ genes in HEK293 cells expressing polyglutamine74exon1 huntingtin (polyQ74htt). Flourescence\u00a0microscopy analysis revealed that KO of DNAJB6 resulted in a 5-fold increase in polyQ74htt aggregation and that DNAJA1 KO resulted in a 4-fold decrease of polyQ74htt aggregation. KO of DNAJB1 did not change the propensity of polyQ74htt to aggregate in cells. These findings where confirmed both by fluorescence microscopy analysis and filter trap assay (FTA). DNAJB6 KO cells displayed an increased rate of cell death as assessed by trypan blue exclusion and propidium iodide (PI) uptake assays. These results demonstrate that the DNAJ proteins DNAJA1 and DNAJB6 can modulate polyQ aggregation in opposite manners, and thus that fine-tuning the cellular levels of DNAJ proteins is critical for suppression of polyQ aggregation and cell survival.",
+ "publisher": "PloS one",
+ "issn": "1932-6203",
+ "date": "2015-04-10",
+ "abstract": "Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin gene. Major pathological hallmarks of HD include inclusions of mutant huntingtin (mHTT) protein, loss of neurons predominantly in the caudate nucleus, and atrophy of multiple brain regions. However, the early sequence of histological events that manifest in region- and cell-specific manner has not been well characterized. Here we use a high-content histological approach to precisely monitor changes in HTT expression and characterize deposition dynamics of mHTT protein inclusion bodies in the recently characterized zQ175 knock-in mouse line. We carried out an automated multi-parameter quantitative analysis of individual cortical and striatal cells in tissue slices from mice aged 2-12 months and confirmed biochemical reports of an age-associated increase in mHTT inclusions in this model. We also found distinct regional and subregional dynamics for inclusion number, size and distribution with subcellular resolution. We used viral-mediated suppression of total HTT in the striatum of zQ175 mice as an example of a therapeutically-relevant but heterogeneously transducing strategy to demonstrate successful application of this platform to quantitatively assess target engagement and outcome on a cellular basis.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32424160"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25859666"
},
{
- "id": "pmid:32102602",
+ "id": "pmid:25800750",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/32102602",
- "title": "Alcohol Use, Mental Health, and Functional Capacity as Predictors of Workplace Disability in a Cohort With Manifest Huntington's Disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25800750",
+ "title": "Cardiac Fas-Dependent and Mitochondria-Dependent Apoptotic Pathways in a Transgenic Mouse Model of Huntington's Disease.",
"type": "article-journal",
- "doi": "10.1176/appi.neuropsych.19090199",
+ "doi": "10.1007/s12012-015-9318-y",
"authors": [
- ["Anita M Y", "Goh"],
- ["Emily", "You"],
- ["Stephanie", "Perin"],
- ["Nicola T", "Lautenschlager"],
- ["Fiona J", "Clay"],
- ["Samantha M", "Loi"],
- ["Terence", "Chong"],
- ["David", "Ames"],
- ["Edmond", "Chiu"],
- ["Kathryn A", "Ellis"]
+ ["Bor-Tsang", "Wu"],
+ ["Ming-Chang", "Chiang"],
+ ["Ching-Yi", "Tasi"],
+ ["Chia-Hua", "Kuo"],
+ ["Woei-Cherng", "Shyu"],
+ ["Chung-Lan", "Kao"],
+ ["Chih-Yang", "Huang"],
+ ["Shin-Da", "Lee"]
],
- "publisher": "The Journal of neuropsychiatry and clinical neurosciences",
- "issn": "1545-7222",
- "date": "2020-02-27",
- "abstract": "Huntington's disease (HD) is an inherited neurodegenerative disease involving motor, cognitive, psychiatric, and behavioral impairments that eventually affect work-role functioning. There is limited research regarding predictors of workplace disability in HD. The authors examined predictors of work impairment and disability in a cross-sectional cohort of employed persons with symptomatic HD participating in the worldwide Enroll-HD study.",
+ "publisher": "Cardiovascular toxicology",
+ "issn": "1559-0259",
+ "date": "2016-04-01",
+ "abstract": "Huntington's disease is an autosomal dominant neurodegenerative disease caused by a CAG repeat expansion in the huntingtin gene. Heart disease is the second leading cause of death in patients with Huntington's disease. This study was to evaluate whether cardiac Fas-dependent and mitochondria-dependent apoptotic pathways are activated in transgenic mice with Huntington's disease. Sixteen Huntington's disease transgenic mice (HD) and sixteen wild-type (WT) littermates were studied at 10.5\u00a0weeks of age. The cardiac characteristics, myocardial architecture, and two major apoptotic pathways in the excised left ventricle from mice were measured by histopathological analysis, Western blotting, and TUNEL assays. The whole heart weight and the left ventricular weight decreased significantly in the HD group, as compared to the WT group. Abnormal myocardial architecture, enlarged interstitial spaces, and more cardiac TUNEL-positive cells were observed in the HD group. The key components of Fas-dependent apoptosis (TNF-alpha, TNFR1, Fas ligand, Fas death receptors, FADD, activated caspase-8, and activated caspase-3) and the key components of mitochondria-dependent apoptosis (Bax, Bax-to-Bcl-2 ratio, cytosolic cytochrome c, activated caspase-9, and activated caspase-3) increased significantly in the hearts of the HD group. Cardiac Fas-dependent and mitochondria-dependent apoptotic pathways were activated in transgenic mice with Huntington's disease, which might provide one of possible mechanisms to explain why patients with Huntington's disease will develop heart failure.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32102602"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25800750"
},
{
- "id": "pmid:31893246",
+ "id": "pmid:25767004",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/31893246",
- "title": "Preimplantation genetic testing for Huntington disease: the perspective of one Portuguese center.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25767004",
+ "title": "Noninvasive prenatal diagnosis of Huntington disease: detection of the paternally inherited expanded CAG repeat in maternal plasma.",
"type": "article-journal",
- "doi": "10.1097/j.pbj.0000000000000048",
+ "doi": "10.1002/pd.4593",
"authors": [
- ["Diogo", "Ferreira"],
- ["Berta", "Carvalho"],
- ["Ana P", "Neto"],
- ["Joaquina", "Silva"],
- ["Ana M", "P\u00f3voa"],
- ["Alberto", "Barros"],
- ["Filipa", "Carvalho"]
+ ["Jessica M E", "van den Oever"],
+ ["Emilia K", "Bijlsma"],
+ ["Ilse", "Feenstra"],
+ ["Nienke", "Muntjewerff"],
+ ["Inge B", "Mathijssen"],
+ ["Egbert", "Bakker"],
+ ["Martine J", "van Belzen"],
+ ["Elles M J", "Boon"]
],
- "publisher": "Porto biomedical journal",
- "issn": "2444-8672",
- "date": "2019-09-04",
- "abstract": "Huntington disease (HD) is an autosomal dominant late-onset neurodegenerative disease caused by an unstable cytosine-adenine-guanine trinucleotide repeat expansion in the huntingtin (",
+ "publisher": "Prenatal diagnosis",
+ "issn": "1097-0223",
+ "date": "2015-04-05",
+ "abstract": "With a shift towards noninvasive testing, we have explored and validated the use of noninvasive prenatal diagnosis (NIPD) for Huntington disease (HD).",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31893246"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25767004"
},
{
- "id": "pmid:31844074",
+ "id": "pmid:25703232",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/31844074",
- "title": "Assessing average somatic CAG repeat instability at the protein level.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25703232",
+ "title": "Neonatal iron supplementation potentiates oxidative stress, energetic dysfunction and neurodegeneration in the R6/2 mouse model of Huntington's disease.",
"type": "article-journal",
- "doi": "10.1038/s41598-019-55202-x",
+ "doi": "10.1016/j.redox.2015.02.002",
"authors": [
- ["Hubert", "Aviolat"],
- ["Ricardo Mouro", "Pinto"],
- ["Elizabeth", "Godschall"],
- ["Ryan", "Murtha"],
- ["Hannah E", "Richey"],
- ["Ellen", "Sapp"],
- ["Petr", "Vodicka"],
- ["Vanessa C", "Wheeler"],
- ["Kimberly B", "Kegel-Gleason"],
- ["Marian", "DiFiglia"]
- ],
- "publisher": "Scientific reports",
- "issn": "2045-2322",
- "date": "2019-12-16",
- "abstract": "Sandwich ELISA-based methods use Abs that target the expanded polyglutamine (polyQ) tract to quantify mutant huntingtin (mHTT). Using Meso Scale Discovery\u00a0(MSD) assay, the mHTT signal detected with MW1 Ab correlated with polyQ length and doubled with a difference of only 7 glutamine residues between equivalent amounts of purified mHTTexon1 proteins. Similar polyQ length-dependent effects on MSD signals were confirmed using endogenous full length mHTT from brains of Huntington's disease (HD) knock-in (KI) mice. We used this avidity bias to devise a method to assess average CAG repeat instability at the protein level in a mixed population of HTT proteins present in tissues. Signal detected for average polyQ length quantification at the protein level by our method exhibited a strong correlation with average CAG repeat length at the genomic DNA level determined by PCR method in striatal tissue homogenates from Hdh",
+ ["Kiersten L", "Berggren"],
+ ["Jianfang", "Chen"],
+ ["Julia", "Fox"],
+ ["Jonathan", "Miller"],
+ ["Lindsay", "Dodds"],
+ ["Bryan", "Dugas"],
+ ["Liset", "Vargas"],
+ ["Amber", "Lothian"],
+ ["Erin", "McAllum"],
+ ["Irene", "Volitakis"],
+ ["Blaine", "Roberts"],
+ ["Ashley I", "Bush"],
+ ["Jonathan H", "Fox"]
+ ],
+ "publisher": "Redox biology",
+ "issn": "2213-2317",
+ "date": "2015-02-11",
+ "abstract": "Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion that encodes a polyglutamine tract in huntingtin (htt) protein. Dysregulation of brain iron homeostasis, oxidative stress and neurodegeneration are consistent features of the HD phenotype. Therefore, environmental factors that exacerbate oxidative stress and iron dysregulation may potentiate HD. Iron supplementation in the human population is common during infant and adult-life stages. In this study, iron supplementation in neonatal HD mice resulted in deterioration of spontaneous motor running activity, elevated levels of brain lactate and oxidized glutathione consistent with increased energetic dysfunction and oxidative stress, and increased striatal and motor cortical neuronal atrophy, collectively demonstrating potentiation of the disease phenotype. Oxidative stress, energetic, and anatomic markers of degeneration were not affected in wild-type littermate iron-supplemented mice. Further, there was no effect of elevated iron intake on disease outcomes in adult HD mice. We have demonstrated an interaction between the mutant huntingtin gene and iron supplementation in neonatal HD mice. Findings indicate that elevated neonatal iron intake potentiates mouse HD and promotes oxidative stress and energetic dysfunction in brain. Neonatal-infant dietary iron intake level may be an environmental modifier of human HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31844074"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25703232"
},
{
- "id": "pmid:31728006",
+ "id": "pmid:25662336",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/31728006",
- "title": "Discovery of a potent small molecule inhibiting Huntington's disease\u00a0(HD) pathogenesis via targeting CAG repeats RNA and Poly Q protein.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25662336",
+ "title": "Age-, tissue- and length-dependent bidirectional somatic CAG\u2022CTG repeat instability in an allelic series of R6/2 Huntington disease mice.",
"type": "article-journal",
- "doi": "10.1038/s41598-019-53410-z",
+ "doi": "10.1016/j.nbd.2015.01.004",
"authors": [
- ["Eshan", "Khan"],
- ["Subodh Kumar", "Mishra"],
- ["Ribhav", "Mishra"],
- ["Amit", "Mishra"],
- ["Amit", "Kumar"]
+ ["Eloise", "Larson"],
+ ["Ian", "Fyfe"],
+ ["A Jennifer", "Morton"],
+ ["Darren G", "Monckton"]
],
- "publisher": "Scientific reports",
- "issn": "2045-2322",
- "date": "2019-11-14",
- "abstract": "CAG repeats RNA causes various fatal neurodegenerative diseases exemplified by Huntington's disease (HD) and several spinocerebellar ataxias (SCAs). Although there are differences in the pathogenic mechanisms, these diseases share the common cause, i.e., expansion of CAG repeats. The shared cause of these diseases raises the possibility for the exploiting the common target as a potential therapeutic approach. Oligonucleotide-based therapeutics are designed earlier with the help of the base pairing rule but are not very promiscuous, considering the nonspecific stimulation of the immune system and the poor cellular delivery. Therefore, small molecules-based therapeutics are preferred for targeting the repeats expansion disorders. Here, we have used the chemical similarity search approach to discern the small molecules that selectively target toxic CAG RNA. The lead compounds showed the specificity towards AA mismatch in biophysical studies including CD, ITC, and NMR spectroscopy and thus aided to forestall the polyQ mediated pathogenicity. Furthermore, the lead compounds also explicitly alleviate the polyQ mediated toxicity in HD cell models and patient-derived cells. These findings suggest that the lead compound could act as a chemical probe for AA mismatch containing RNA as well as plays a neuroprotective role in fatal neurodegenerative diseases like HD and SCAs.",
+ "publisher": "Neurobiology of disease",
+ "issn": "1095-953X",
+ "date": "2015-02-03",
+ "abstract": "The expansion of simple sequence CAG\u2022CTG repeats is associated with a number of inherited disorders including Huntington disease (HD), myotonic dystrophy type 1 and several of the spinocerebellar ataxias. Inherited disease-associated alleles usually exceed 40 repeats and may be in excess of 1,000 repeats in some disorders. Inherited allele length is inversely proportional to age at onset, and frequent germline expansions account for the striking anticipation observed in affected families. Expanded disease associated alleles are also somatically unstable via a pathway that is age dependent and tissue specific, and also appears to be expansion biased. Somatic expansions are thought to contribute toward both tissue specificity and disease progression. Here we have examined the somatic mutational dynamics in brain and peripheral tissues from an allelic series of R6/2 HD transgenic mice inheriting from 52 to >700 CAG repeats. We found age-dependent, tissue-specific somatic instability, with particularly large expansions observed in the striatum and cortex. We also found a positive increase in somatic instability with increasing allele length. Surprisingly, however, the degree of somatic variation did not increase in a linear fashion, but leveled off with increasing allele length. Most unexpectedly, the almost exclusive bias toward the accumulation of expansions observed in mice inheriting smaller alleles was lost, and a high frequency of large somatic contractions was observed in mice inheriting very large alleles (>500 repeats). These data highlight the bidirectional nature of CAG\u2022CTG repeat instability and the subtle balance that exists between expansion and contraction in vivo. Defining the dynamics and tissue specificity of expansion and contraction is important for understanding the role of genetic instability in pathophysiology and in particular the development of novel therapies based on suppressing expansions and/or promoting contractions.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31728006"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25662336"
},
{
- "id": "pmid:31722751",
+ "id": "pmid:25642374",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/31722751",
- "title": "Chromatin accessibility and transcription dynamics during in vitro astrocyte differentiation of Huntington's Disease Monkey pluripotent stem cells.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25642374",
+ "title": "Trinucleotide repeats and haplotypes at the huntingtin locus in an Indian sample overlaps with European haplogroup a.",
"type": "article-journal",
- "doi": "10.1186/s13072-019-0313-6",
+ "doi": "10.1371/currents.hd.a3ad1a381ab1eed117675145318c9a80",
"authors": [
- ["Alexandra V", "Goodnight"],
- ["Isaac", "Kremsky"],
- ["Sujittra", "Khampang"],
- ["Yoon Hee", "Jung"],
- ["James M", "Billingsley"],
- ["Steven E", "Bosinger"],
- ["Victor G", "Corces"],
- ["Anthony W S", "Chan"]
+ ["Nagaraj S", "Moily"],
+ ["Lakshmi Narayanan", "Kota"],
+ ["Ram Murthy", "Anjanappa"],
+ ["Sowmya", "Venugopal"],
+ ["Radhika", "Vaidyanathan"],
+ ["Pramod", "Pal"],
+ ["Meera", "Purushottam"],
+ ["Sanjeev", "Jain"],
+ ["Mahesh", "Kandasamy"]
],
- "publisher": "Epigenetics & chromatin",
- "issn": "1756-8935",
- "date": "2019-11-13",
- "abstract": "Huntington's Disease (HD) is a fatal neurodegenerative disorder caused by a CAG repeat expansion, resulting in a mutant huntingtin protein. While it is now clear that astrocytes are affected by HD and significantly contribute to neuronal dysfunction and pathogenesis, the alterations in the transcriptional and epigenetic profiles in HD astrocytes have yet to be characterized. Here, we examine global transcription and chromatin accessibility dynamics during in vitro astrocyte differentiation in a transgenic non-human primate model of HD.",
+ "publisher": "PLoS currents",
+ "issn": "2157-3999",
+ "date": "2014-09-24",
+ "abstract": "Huntington's disease (HD), an autosomal dominant neurodegenerative syndrome, has a world-wide distribution. An estimated 2.5-10/100,000 people of European ancestry are affected with HD, while the Asian populations have lower prevalence (0.6-3.8/100,000). The epidemiology of HD is not well described in India, and the distribution of the pathogenic CAG expansion, and the associated haplotype, in this population needs to be better understood. This study demonstrates a distribution of CAG repeats, at the HTT locus, comparable to the European population in both normal and HD affected chromosomes. Further, we provide an evidence for similarity of the HD halpotype in Indian sample to the European HD haplogroup.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31722751"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25642374"
},
{
- "id": "pmid:31599037",
+ "id": "pmid:25574027",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/31599037",
- "title": "Expanded polyglutamine impairs normal nuclear distribution of fused in sarcoma and poly (rC)-binding protein 1 in Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25574027",
+ "title": "Htt CAG repeat expansion confers pleiotropic gains of mutant huntingtin function in chromatin regulation.",
"type": "article-journal",
- "doi": "10.1111/neup.12600",
+ "doi": "10.1093/hmg/ddv006",
"authors": [
- ["Shinichiro", "Mori"],
- ["Hiroyuki", "Honda"],
- ["Takashi", "Ishii"],
- ["Motoi", "Yoshimura"],
- ["Naokazu", "Sasagasako"],
- ["Satoshi O", "Suzuki"],
- ["Takayuki", "Taniwaki"],
- ["Toru", "Iwaki"]
+ ["Marta", "Biagioli"],
+ ["Francesco", "Ferrari"],
+ ["Eric M", "Mendenhall"],
+ ["Yijing", "Zhang"],
+ ["Serkan", "Erdin"],
+ ["Ravi", "Vijayvargia"],
+ ["Sonia M", "Vallabh"],
+ ["Nicole", "Solomos"],
+ ["Poornima", "Manavalan"],
+ ["Ashok", "Ragavendran"],
+ ["Fatih", "Ozsolak"],
+ ["Jong Min", "Lee"],
+ ["Michael E", "Talkowski"],
+ ["James F", "Gusella"],
+ ["Marcy E", "Macdonald"],
+ ["Peter J", "Park"],
+ ["Ihn Sik", "Seong"]
],
- "publisher": "Neuropathology : official journal of the Japanese Society of Neuropathology",
- "issn": "1440-1789",
- "date": "2019-10-09",
- "abstract": "Huntington's disease (HD) is an inherited neurodegenerative disease caused by a polyglutamine repeat expansion in the huntingtin protein. Immunohistochemical studies using the 1C2 antibody for polyglutamine expansion have detected characteristic intranuclear inclusions (INIs) in affected neurons in HD. Further, in vitro and mouse models of HD have shown that the INIs recruit several proteins relating to RNA splicing and translation. In the present study, we immunohistochemically investigated the association of INIs with various heterogeneous nuclear ribonucleoproteins in the cerebral cortex of four autopsy cases of HD. Fused in sarcoma (FUS) was colocalized with 1C2-positive nuclear inclusions in all examined cases. Localization of poly (rC)-binding protein 1 (PCBP1) in 1C2-positive nuclear inclusions was also observed. Double immunofluorescence revealed complete or partial loss of the normal, diffuse nuclear distribution of FUS or PCBP1 in neurons with 1C2-positive nuclear inclusions. This maldistribution of FUS in cortical neurons suggests a severe disturbance of messenger RNA processing, which may be a common pathogenetic mechanism of FUS-related familial amyotrophic lateral sclerosis.",
+ "publisher": "Human molecular genetics",
+ "issn": "1460-2083",
+ "date": "2015-01-08",
+ "abstract": "The CAG repeat expansion in the Huntington's disease gene HTT extends a polyglutamine tract in mutant huntingtin that enhances its ability to facilitate polycomb repressive complex 2 (PRC2). To gain insight into this dominant gain of function, we mapped histone modifications genome-wide across an isogenic panel of mouse embryonic stem cell (ESC) and neuronal progenitor cell (NPC) lines, comparing the effects of Htt null and different size Htt CAG mutations. We found that Htt is required in ESC for the proper deposition of histone H3K27me3 at a subset of 'bivalent' loci but in NPC it is needed at 'bivalent' loci for both the proper maintenance and the appropriate removal of this mark. In contrast, Htt CAG size, though changing histone H3K27me3, is prominently associated with altered histone H3K4me3 at 'active' loci. The sets of ESC and NPC genes with altered histone marks delineated by the lack of huntingtin or the presence of mutant huntingtin, though distinct, are enriched in similar pathways with apoptosis specifically highlighted for the CAG mutation. Thus, the manner by which huntingtin function facilitates PRC2 may afford mutant huntingtin with multiple opportunities to impinge upon the broader machinery that orchestrates developmentally appropriate chromatin status.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31599037"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25574027"
},
{
- "id": "pmid:31586340",
+ "id": "pmid:25464109",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/31586340",
- "title": "Tracking Expansions of Stable and Threshold Length Trinucleotide Repeat Tracts In Vivo and In Vitro Using Saccharomyces cerevisiae.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25464109",
+ "title": "A new mutation for Huntington disease following maternal transmission of an intermediate allele.",
"type": "article-journal",
- "doi": "10.1007/978-1-4939-9784-8_3",
+ "doi": "10.1016/j.ejmg.2014.11.005",
"authors": [
- ["Gregory M", "Williams"],
- ["Athena K", "Petrides"],
- ["Lata", "Balakrishnan"],
- ["Jennifer A", "Surtees"]
+ ["Alicia", "Semaka"],
+ ["Chris", "Kay"],
+ ["Ren\u00e9 D M", "Belfroid"],
+ ["Emilia K", "Bijlsma"],
+ ["Monique", "Losekoot"],
+ ["Irene M", "van Langen"],
+ ["Merel C", "van Maarle"],
+ ["Mayke", "Oosterloo"],
+ ["Michael R", "Hayden"],
+ ["Martine J", "van Belzen"]
],
- "publisher": "Methods in molecular biology (Clifton, N.J.)",
- "issn": "1940-6029",
- "date": "2020-01-01",
- "abstract": "Trinucleotide repeat (TNR) tracts are inherently unstable during DNA replication, leading to repeat expansions and/or contractions. Expanded tracts are the cause of over 40 neurodegenerative and neuromuscular diseases. In this chapter, we focus on the (CAG)",
+ "publisher": "European journal of medical genetics",
+ "issn": "1878-0849",
+ "date": "2014-11-20",
+ "abstract": "New mutations for Huntington disease (HD) originate from CAG repeat expansion of intermediate alleles (27-35 CAG). Expansions of such alleles into the pathological range (\u2265 36 CAG) have been exclusively observed in paternal transmission. We report the occurrence of a new mutation that defies the paternal expansion bias normally observed in HD. A maternal intermediate allele with 33 CAG repeats expanded in transmission to 48 CAG repeats causing a de novo case of HD in the family. Retrospectively, the mother presented with cognitive decline, but HD was never considered in the differential diagnosis. She was diagnosed with dementia and testing for HD was only performed after her daughter had been diagnosed. This observation of an intermediate allele expanding into the full penetrance HD range after maternal transmission has important implications for genetic counselling of females with intermediate repeats.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31586340"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25464109"
},
{
- "id": "pmid:31403680",
+ "id": "pmid:25453459",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/31403680",
- "title": "Association of CAG Repeats With Long-term Progression in Huntington Disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25453459",
+ "title": "Prediction of manifest Huntington's disease with clinical and imaging measures: a prospective observational study.",
"type": "article-journal",
- "doi": "10.1001/jamaneurol.2019.2368",
+ "doi": "10.1016/s1474-4422(14)70238-8",
"authors": [
- ["Douglas R", "Langbehn"],
- ["Julie C", "Stout"],
- ["Sarah", "Gregory"],
- ["James A", "Mills"],
- ["Alexandra", "Durr"],
- ["Blair R", "Leavitt"],
- ["Raymund A C", "Roos"],
+ ["Jane S", "Paulsen"],
["Jeffrey D", "Long"],
- ["Gail", "Owen"],
+ ["Christopher A", "Ross"],
+ ["Deborah L", "Harrington"],
+ ["Cheryl J", "Erwin"],
+ ["Janet K", "Williams"],
+ ["Holly James", "Westervelt"],
["Hans J", "Johnson"],
- ["Beth", "Borowsky"],
- ["David", "Craufurd"],
- ["Ralf", "Reilmann"],
- ["G Bernhard", "Landwehrmeyer"],
- ["Rachael I", "Scahill"],
- ["Sarah J", "Tabrizi"]
+ ["Elizabeth H", "Aylward"],
+ ["Ying", "Zhang"],
+ ["H Jeremy", "Bockholt"],
+ ["Roger A", "Barker"]
],
- "publisher": "JAMA neurology",
- "issn": "2168-6157",
- "date": "2019-11-01",
- "abstract": "In Huntington disease (HD), mutation severity is defined by the length of the CAG trinucleotide sequence, a well-known predictor of clinical onset age. The association with disease trajectory is less well characterized. Quantifiable summary measures of trajectory applicable over decades of early disease progression are lacking. An accurate model of the age-CAG association with early progression is critical to clinical trial design, informing both sample size and intervention timing.",
+ "publisher": "The Lancet. Neurology",
+ "issn": "1474-4465",
+ "date": "2014-11-03",
+ "abstract": "Although the association between cytosine-adenine-guanine (CAG) repeat length and age at onset of Huntington's disease is well known, improved prediction of onset would be advantageous for clinical trial design and prognostic counselling. We compared various measures for tracking progression and predicting conversion to manifest Huntington's disease.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31403680"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25453459"
},
{
- "id": "pmid:31379510",
+ "id": "pmid:25385587",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/31379510",
- "title": "The Onset and Progression of Hippocampal Synaptic Plasticity Deficits in the Q175FDN Mouse Model of Huntington Disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25385587",
+ "title": "Potential function for the Huntingtin protein as a scaffold for selective autophagy.",
"type": "article-journal",
- "doi": "10.3389/fncel.2019.00326",
+ "doi": "10.1073/pnas.1420103111",
"authors": [
- ["Jade G", "Quirion"],
- ["Matthew P", "Parsons"]
+ ["Joseph", "Ochaba"],
+ ["Tam\u00e1s", "Lukacsovich"],
+ ["George", "Csikos"],
+ ["Shuqiu", "Zheng"],
+ ["Julia", "Margulis"],
+ ["Lisa", "Salazar"],
+ ["Kai", "Mao"],
+ ["Alice L", "Lau"],
+ ["Sylvia Y", "Yeung"],
+ ["Sandrine", "Humbert"],
+ ["Fr\u00e9d\u00e9ric", "Saudou"],
+ ["Daniel J", "Klionsky"],
+ ["Steven", "Finkbeiner"],
+ ["Scott O", "Zeitlin"],
+ ["J Lawrence", "Marsh"],
+ ["David E", "Housman"],
+ ["Leslie M", "Thompson"],
+ ["Joan S", "Steffan"]
],
- "publisher": "Frontiers in cellular neuroscience",
- "issn": "1662-5102",
- "date": "2019-07-17",
- "abstract": "Huntington disease (HD) is an inherited neurodegenerative disease characterized by a clinical triad of motor, psychiatric and cognitive symptoms. HD is caused by a CAG repeat expansion in the gene encoding the huntingtin protein. Homozygosity for the HD-causing mutation is extremely rare; thus, the majority of HD patients express the mutant huntingtin protein in addition to reduced levels of the non-pathogenic huntingtin protein. Deficits in synaptic plasticity, including hippocampal long-term potentiation (LTP), have been identified in various mouse models of HD and are thought to contribute to the debilitating cognitive symptoms associated with the disease. However, the bulk of these studies used N-terminal fragment or homozygous knock-in mouse models of HD at symptomatic ages, and our understanding of the onset and progression of synaptic plasticity deficits in the HD brain is lacking. To better understand the time-course of synaptic plasticity deficits in HD, as well as the impact of heterozygous and homozygous huntingtin mutations, we quantified basal synaptic connectivity, presynaptic release probability, presynaptically mediated post-tetanic potentiation (PTP) and postsynaptically mediated LTP at presymptomatic, early symptomatic and late symptomatic ages in heterozygous and homozygous Q175FDN knock-in HD mice. Our results demonstrate clear age-dependent effects of the HD-causing mutation on both short and long-term plasticity that generally emerge earlier in homozygous mice. Interestingly, deficits in presynaptic short-term plasticity were more closely linked to disease progression than deficits in postsynaptic LTP, and heterozygous mice were more susceptible to an LTP deficit when induced by high frequency stimulation compared to theta burst stimulation. To the best of our knowledge, the present study represents the most thorough characterization to date of the onset and progression of hippocampal synaptic plasticity deficits in a mouse model of HD, and should prove valuable to future studies exploring cellular mechanisms underlying the debilitating cognitive decline in HD.",
+ "publisher": "Proceedings of the National Academy of Sciences of the United States of America",
+ "issn": "1091-6490",
+ "date": "2014-11-10",
+ "abstract": "Although dominant gain-of-function triplet repeat expansions in the Huntingtin (HTT) gene are the underlying cause of Huntington disease (HD), understanding the normal functions of nonmutant HTT protein has remained a challenge. We report here findings that suggest that HTT plays a significant role in selective autophagy. Loss of HTT function in Drosophila disrupts starvation-induced autophagy in larvae and conditional knockout of HTT in the mouse CNS causes characteristic cellular hallmarks of disrupted autophagy, including an accumulation of striatal p62/SQSTM1 over time. We observe that specific domains of HTT have structural similarities to yeast Atg proteins that function in selective autophagy, and in particular that the C-terminal domain of HTT shares structural similarity to yeast Atg11, an autophagic scaffold protein. To explore possible functional similarity between HTT and Atg11, we investigated whether the C-terminal domain of HTT interacts with mammalian counterparts of yeast Atg11-interacting proteins. Strikingly, this domain of HTT coimmunoprecipitates with several key Atg11 interactors, including the Atg1/Unc-51-like autophagy activating kinase 1 kinase complex, autophagic receptor proteins, and mammalian Atg8 homologs. Mutation of a phylogenetically conserved WXXL domain in a C-terminal HTT fragment reduces coprecipitation with mammalian Atg8 homolog GABARAPL1, suggesting a direct interaction. Collectively, these data support a possible central role for HTT as an Atg11-like scaffold protein. These findings have relevance to both mechanisms of disease pathogenesis and to therapeutic intervention strategies that reduce levels of both mutant and normal HTT.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31379510"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25385587"
},
{
- "id": "pmid:31108174",
+ "id": "pmid:25322077",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/31108174",
- "title": "Pridopidine protects neurons from mutant-huntingtin toxicity via the sigma-1 receptor.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25322077",
+ "title": "The phosphodiesterase 10 positron emission tomography tracer, [18F]MNI-659, as a novel biomarker for early Huntington disease.",
"type": "article-journal",
- "doi": "10.1016/j.nbd.2019.05.009",
+ "doi": "10.1001/jamaneurol.2014.1954",
"authors": [
- ["Chelsy R", "Eddings"],
- ["Nicolas", "Arbez"],
- ["Sergey", "Akimov"],
- ["Michal", "Geva"],
- ["Michael R", "Hayden"],
- ["Christopher A", "Ross"]
- ],
- "publisher": "Neurobiology of disease",
- "issn": "1095-953X",
- "date": "2019-05-17",
- "abstract": "Huntington's disease (HD) is a neurodegenerative disease caused by a CAG repeat expansion in the Huntingtin gene (HTT), translated into a Huntingtin protein with a polyglutamine expansion. There is preferential loss of medium spiny neurons within the striatum and cortical pyramidal neurons. Pridopidine is a small molecule showing therapeutic potential in HD preclinical and clinical studies. Pridopidine has nanomolar affinity to the sigma-1 receptor (sigma-1R), which is located predominantly at the endoplasmic reticulum (ER) and mitochondrial associated ER membrane, and activates neuroprotective pathways. Here we evaluate the neuroprotective effects of pridopidine against mutant Huntingtin toxicity in mouse and human derived in vitro cell models. We also investigate the involvement of the sigma-1 receptor in the mechanism of pridopidine. Pridopidine protects mutant Huntingtin transfected mouse primary striatal and cortical neurons, with an EC50 in the mid nanomolar range, as well as HD patient-derived induced pluripotent stem cells (iPSCs). This protection by pridopidine is blocked by NE-100, a purported sigma-1 receptor antagonist, and not blocked by ANA-12, a reported TrkB receptor antagonist. 3PPP, a documented sigma-1 receptor agonist, shows similar neuroprotective effects. Genetic knock out of the sigma-1 receptor dramatically decreases protection from pridopidine and 3PPP, but not protection via brain derived neurotrophic factor (BDNF). The neuroprotection afforded by pridopidine in our HD cell models is robust and sigma-1 receptor dependent. These studies support the further development of pridopidine, and other sigma-1 receptor agonists as neuroprotective agents for HD and perhaps for other disorders.",
+ ["David S", "Russell"],
+ ["Olivier", "Barret"],
+ ["Danna L", "Jennings"],
+ ["Joseph H", "Friedman"],
+ ["Gilles D", "Tamagnan"],
+ ["David", "Thomae"],
+ ["David", "Alagille"],
+ ["Thomas J", "Morley"],
+ ["Caroline", "Papin"],
+ ["Spyridon", "Papapetropoulos"],
+ ["Rikki N", "Waterhouse"],
+ ["John P", "Seibyl"],
+ ["Kenneth L", "Marek"]
+ ],
+ "publisher": "JAMA neurology",
+ "issn": "2168-6157",
+ "date": "2014-12-01",
+ "abstract": "In Huntington disease (HD) striatal neuron loss precedes and predicts motor signs or symptoms. Current imaging biomarkers lack adequate sensitivity for assessing the early stages of HD. Developing an imaging biomarker for HD spanning the time of onset of motor signs remains a major unmet research need. Intracellular proteins whose expression is altered by the mutant huntingtin protein may be superior markers for early HD stages.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31108174"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25322077"
},
{
- "id": "pmid:31103960",
+ "id": "pmid:25316307",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/31103960",
- "title": "Clinical phenotype in carriers of intermediate alleles in the huntingtin gene.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25316307",
+ "title": "Sexually dimorphic dopaminergic dysfunction in a transgenic mouse model of Huntington's disease.",
"type": "article-journal",
- "doi": "10.1016/j.jns.2019.05.010",
+ "doi": "10.1016/j.pbb.2014.10.004",
"authors": [
- ["Daniel", "Savitt"],
- ["Joseph", "Jankovic"]
+ ["Thibault", "Renoir"],
+ ["Andrew", "Argyropoulos"],
+ ["Caroline", "Chevarin"],
+ ["Laurence", "Lanfumey"],
+ ["Anthony J", "Hannan"]
],
- "publisher": "Journal of the neurological sciences",
- "issn": "1878-5883",
- "date": "2019-05-13",
- "abstract": "To describe the phenotype of individuals with intermediate allele (IA) CAG repeat length in the huntingtin (HTT) gene evaluated at the Parkinson's Disease Center and Movement Disorders Clinic (PDCMDC) at Baylor College of Medicine (BCM).",
+ "publisher": "Pharmacology, biochemistry, and behavior",
+ "issn": "1873-5177",
+ "date": "2014-10-12",
+ "abstract": "Using the R6/1 transgenic mouse model of Huntington's disease (HD), we have recently shown that acute administration with the dopamine-norepinephrine reuptake inhibitor bupropion was able to rescue depressive-like behaviours in female HD mice at 12weeks of age.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31103960"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25316307"
},
{
- "id": "pmid:30961637",
+ "id": "pmid:25300330",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/30961637",
- "title": "Modulation of mTOR and CREB pathways following mGluR5 blockade contribute to improved Huntington's pathology in zQ175 mice.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25300330",
+ "title": "Huntingtin Supplies a csaA-Independent Function Essential for EDTA-Resistant Homotypic Cell Adhesion in Dictyostelium discoideum.",
"type": "article-journal",
- "doi": "10.1186/s13041-019-0456-1",
+ "doi": "10.3233/jhd-140112",
"authors": [
- ["Khaled S", "Abd-Elrahman"],
- ["Stephen S G", "Ferguson"]
+ ["Morgan N", "Thompson"],
+ ["Marcy E", "MacDonald"],
+ ["James F", "Gusella"],
+ ["Michael A", "Myre"]
],
- "publisher": "Molecular brain",
- "issn": "1756-6606",
- "date": "2019-04-08",
- "abstract": "Huntington's disease (HD) is a neurodegenerative disorder caused by a genetic abnormality in the huntingtin gene that leads to a polyglutamine repeat expansion of the huntingtin protein. The cleaved polyglutamine expansion of mutant huntingtin (mHTT) protein can form aggregates strongly correlated with HD progression. We have previously shown that the inhibition of mGluR5 using CTEP, a selective negative allosteric mGluR5 modulator, can delay disease progression and reduce in mHTT aggregates in the zQ175 mouse model of HD. This was paralleled by enhanced catalytic activity of Unc-51-like kinase 1 (ULK1), a kinase modulated by mammalian target of rapamycin (mTOR) and key regulator of autophagy initiation. In the present study, we show that CTEP can correct aberrant phosphoinositide 3-kinase (PI3K)/Akt/mTOR signaling detected in zQ175 mice that may underlie the enhanced ULK1 activity and activation of autophagy. We also show that CTEP can facilitate cAMP response element-binding protein (CREB)-mediated expression of brain-derived neurotrophic factor (BDNF) to foster neuronal survival and reduce apoptosis. Taken together, our findings provide the molecular evidence for how targeting mGluR5 using a well-tolerated selective NAM can mitigate two critical mechanisms of neurodegeneration, autophagy and apoptosis.",
+ "publisher": "Journal of Huntington's disease",
+ "issn": "1879-6400",
+ "date": "2014-01-01",
+ "abstract": "The CAG triplet repeat expansion mutation in the HTT locus, which results in neurodegeneration in Huntington's disease, elongates a polyglutamine tract in huntingtin, a HEAT/HEAT-like protein that has been highly structurally conserved through evolution. In several organisms, huntingtin is necessary for proper cell-cell adhesion and normal development.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30961637"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25300330"
},
{
- "id": "pmid:30867264",
+ "id": "pmid:25136821",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/30867264",
- "title": "Clinical manifestations of homozygote allele carriers in Huntington disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25136821",
+ "title": "Instability of trinucleotidic repeats during chromatin remodeling in spermatids.",
"type": "article-journal",
- "doi": "10.1212/wnl.0000000000007147",
+ "doi": "10.1002/humu.22637",
"authors": [
- ["Esther", "Cubo"],
- ["Saul-Indra", "Martinez-Horta"],
- ["Frederic Sampedro", "Santalo"],
- ["Asunci\u00f3n Mart\u00ednez", "Descalls"],
- ["Sara", "Calvo"],
- ["Cecilia", "Gil-Polo"],
- ["Ignacio", "Mu\u00f1oz"],
- ["Katia", "Llano"],
- ["Natividad", "Mariscal"],
- ["Dolores", "Diaz"],
- ["Aranzazu", "Gutierrez"],
- ["Laura", "Aguado"],
- ["Mar\u00eda A", "Ramos-Arroyo"]
+ ["Olivier", "Simard"],
+ ["Marie-Chantal", "Gr\u00e9goire"],
+ ["M\u00e9lina", "Arguin"],
+ ["Marc-Andr\u00e9", "Brazeau"],
+ ["Fr\u00e9d\u00e9ric", "Leduc"],
+ ["Isabelle", "Marois"],
+ ["Martin V", "Richter"],
+ ["Guylain", "Boissonneault"]
],
- "publisher": "Neurology",
- "issn": "1526-632X",
- "date": "2019-03-13",
- "abstract": "Because patients homozygous for Huntington disease (HD) receive the gain-of-function mutation in a double dose, one would expect a more toxic effect in homozygotes than in heterozygotes. Our aim was to investigate the phenotypic differences between homozygotes with both alleles \u226536 CAG repeats and heterozygotes with 1 allele \u226536 CAG repeats.",
+ "publisher": "Human mutation",
+ "issn": "1098-1004",
+ "date": "2014-09-17",
+ "abstract": "Transient DNA breaks and evidence of DNA damage response have recently been reported during the chromatin remodeling process in haploid spermatids, creating a potential window of enhanced genetic instability. We used flow cytometry to achieve separation of differentiating spermatids into four highly purified populations using transgenic mice harboring 160 CAG repeats within exon 1 of the human Huntington disease gene (HTT). Trinucleotic repeat expansion was found to occur immediately following the chromatin remodeling steps, confirming the genetic instability of the process and pointing to the origin of paternal anticipation observed in some trinucleotidic repeats diseases.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30867264"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25136821"
},
{
- "id": "pmid:30726572",
+ "id": "pmid:25101541",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/30726572",
- "title": "Enhanced striatopallidal gamma-aminobutyric acid (GABA)",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25101541",
+ "title": "Ethological endophenotypes are altered by elevated stress hormone levels in both Huntington's disease and wildtype mice.",
"type": "article-journal",
- "doi": "10.1002/mds.27622",
+ "doi": "10.1016/j.bbr.2014.07.044",
"authors": [
- ["Tamara", "Perez-Rosello"],
- ["Simon", "Gelman"],
- ["Geoffrey", "Tombaugh"],
- ["Roger", "Cachope"],
- ["Vahri", "Beaumont"],
- ["D James", "Surmeier"]
+ ["Christina", "Mo"],
+ ["Thibault", "Renoir"],
+ ["Anthony J", "Hannan"]
],
- "publisher": "Movement disorders : official journal of the Movement Disorder Society",
- "issn": "1531-8257",
- "date": "2019-02-06",
- "abstract": "Huntington's disease (HD) is caused by a CAG repeat expansion in the huntingtin gene. This mutation leads to progressive dysfunction that is largely attributable to dysfunction of the striatum. The earliest signs of striatal pathology in HD are found in indirect pathway gamma-Aminobutyric acid (GABA)-ergic spiny projection neurons that innervate the external segment of the globus pallidus (GPe). What is less clear is whether the synaptic coupling of spiny projection neurons with GPe neurons changes in HD.",
+ "publisher": "Behavioural brain research",
+ "issn": "1872-7549",
+ "date": "2014-08-04",
+ "abstract": "Huntington's disease (HD) is an autosomal dominant, neurodegenerative disorder with cognitive, psychiatric, motor, neuroendocrine and peripheral dysfunctions. Symptom onset and progression can be closely modeled in HD transgenic mice, which facilitate the search for therapeutics and environmental modulators. In the first investigation of chronic stress in HD, we have previously shown that administering a moderate dose of the stress hormone, corticosterone (CORT) had no effect on short-term memory in wildtype (WT) mice but accelerated the onset of the impairment in male R6/1 HD mice. We now extend this investigation to ethological dysfunctions in HD, which we hypothesized to be more susceptible to CORT treatment compared to the same functions in WT littermates. Both genotypes consumed similar doses of CORT dissolved in drinking water across 6-14 weeks of age and were assessed for olfactory sensitivity, nest-building, saccharin preference as well as vocal responses to sociosexual stimuli. In female HD and WT mice, olfactory sensitivity and saccharin preference were reduced by 2 and 4 weeks of CORT, respectively. In males, there was no effect of CORT on saccharin preference, however the number of vocalizations to a female mouse was transiently increased by CORT-drinking, regardless of genotype. Nest-building was severely impaired in HD mice at an early age, but was unaffected by CORT. Our results suggest that the presence of the HD mutation had no bearing on CORT-induced effects at this dose, suggesting that even moderately elevated stress hormone levels can impair ethological behaviors in both the HD and healthy brain.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30726572"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25101541"
},
{
- "id": "pmid:30682531",
+ "id": "pmid:25088714",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/30682531",
- "title": "Emerging differences between Huntington's disease-like 2 and Huntington's disease: A comparison using MRI brain volumetry.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25088714",
+ "title": "Effects of chronic stress on the onset and progression of Huntington's disease in transgenic mice.",
"type": "article-journal",
- "doi": "10.1016/j.nicl.2019.101666",
+ "doi": "10.1016/j.nbd.2014.07.008",
"authors": [
- ["David G", "Anderson"],
- ["Mark", "Haagensen"],
- ["Aline", "Ferreira-Correia"],
- ["Ronald", "Pierson"],
- ["Jonathan", "Carr"],
- ["Amanda", "Krause"],
- ["Russell L", "Margolis"]
+ ["Christina", "Mo"],
+ ["Thibault", "Renoir"],
+ ["Anthony J", "Hannan"]
],
- "publisher": "NeuroImage. Clinical",
- "issn": "2213-1582",
- "date": "2019-01-07",
- "abstract": "Huntington's Disease-Like 2 (HDL2), caused by a CTG/CAG expansion in JPH3 on chromosome 16q24, is the most common Huntington's Disease (HD) phenocopy in populations with African ancestry. Qualitatively, brain MRIs of HDL2 patients have been indistinguishable from HD. To determine brain regions most affected in HDL2 a cross-sectional study using MRI brain volumetry was undertaken to compare the brains of nine HDL2, 11 HD and nine age matched control participants. Participants were ascertained from the region in South Africa with the world's highest HDL2 incidence. The HDL2 and HD patient groups showed no significant differences with respect to mean age at MRI, disease duration, abnormal triplet repeat length, or age at disease onset. Overall, intracerebral volumes were smaller in both affected groups compared to the control group. Comparing the HDL2 and HD groups across multiple covariates, cortical and subcortical volumes were similar with the exception that the HDL2 thalamic volumes were smaller. Consistent with other similarities between the two diseases, these results indicate a pattern of neurodegeneration in HDL2 that is remarkably similar to HD. However smaller thalamic volumes in HDL2 raises intriguing questions into the pathogenesis of both disorders, and how these volumetric differences relate to their respective phenotypes.",
+ "publisher": "Neurobiology of disease",
+ "issn": "1095-953X",
+ "date": "2014-08-01",
+ "abstract": "Huntington's disease (HD) is a neurodegenerative disease caused by a tandem repeat mutation encoding an expanded polyglutamine tract. Our previous work showed that memory deficits in HD transgenic mice could be accelerated by increased levels of stress hormone, while memory in WT mice remained unaffected. HD patients experience higher levels of stress compared to the general population and symptoms of HD also include motor, cognitive, psychiatric, sexual and olfactory abnormalities, and an associated decline in activities of daily living. Therefore we investigated the impact of a robust stressor (i.e. restraint) on the onset and progression of a range of behavioral phenotypes in R6/1 transgenic HD mice. Restraint was administered for 1h daily from 6weeks of age and continued until R6/1 mice were clearly motor symptomatic at 14weeks of age. Serum corticosterone levels in both R6/1 and WT littermates were elevated immediately after the last restraint session and weight gain was suppressed in restrained animals throughout the treatment period. Motor coordination and locomotor activity were enhanced by chronic restraint in males, regardless of genotype. However, there was no effect of restraint on motor performances in female animals. At 8weeks of age, olfactory sensitivity was impaired by restraint in R6/1 HD female mice, but not in WT mice. In male R6/1 mice, the olfactory deficit was exacerbated by restraint and olfaction was also impaired in male WT mice. The development of deficits in saccharin preference, Y-maze memory, nest-building and sexually-motivated vocalizations was unaffected by chronic restraint in R6/1 and had little impact on such behavioral performances in WT animals. We provide evidence that chronic stress can negatively modulate specific endophenotypes in HD mice, while the same functions were affected to a lesser extent in WT mice. This vulnerability in HD animals seems to be sex-specific depending on the stress paradigm used. It is hoped that our work will stimulate clinical investigations into the effects of stress on both pre-symptomatic and symptomatic gene-positive members of HD families, and inform the development of new therapeutic approaches.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30682531"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25088714"
},
{
- "id": "pmid:30618191",
+ "id": "pmid:25035419",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/30618191",
- "title": "Dynamic functional network connectivity in Huntington's disease and its associations with motor and cognitive measures.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25035419",
+ "title": "Phosphorodiamidate morpholino oligomers suppress mutant huntingtin expression and attenuate neurotoxicity.",
"type": "article-journal",
- "doi": "10.1002/hbm.24504",
+ "doi": "10.1093/hmg/ddu349",
"authors": [
- ["Flor A", "Espinoza"],
- ["Jingyu", "Liu"],
- ["Jennifer", "Ciarochi"],
- ["Jessica A", "Turner"],
- ["Victor M", "Vergara"],
- ["Arvind", "Caprihan"],
- ["Maria", "Misiura"],
- ["Hans J", "Johnson"],
- ["Jeffrey D", "Long"],
- ["Jeremy H", "Bockholt"],
- ["Jane S", "Paulsen"],
- ["Vince D", "Calhoun"]
+ ["Xin", "Sun"],
+ ["Leonard O", "Marque"],
+ ["Zachary", "Cordner"],
+ ["Jennifer L", "Pruitt"],
+ ["Manik", "Bhat"],
+ ["Pan P", "Li"],
+ ["Geetha", "Kannan"],
+ ["Ellen E", "Ladenheim"],
+ ["Timothy H", "Moran"],
+ ["Russell L", "Margolis"],
+ ["Dobrila D", "Rudnicki"]
],
- "publisher": "Human brain mapping",
- "issn": "1097-0193",
- "date": "2019-01-07",
- "abstract": "Dynamic functional network connectivity (dFNC) is an expansion of traditional, static FNC that measures connectivity variation among brain networks throughout scan duration. We used a large resting-state fMRI (rs-fMRI) sample from the PREDICT-HD study (N\u2009=\u2009183 Huntington disease gene mutation carriers [HDgmc] and N\u2009=\u200978 healthy control [HC] participants) to examine whole-brain dFNC and its associations with CAG repeat length as well as the product of scaled CAG length and age, a variable representing disease burden. We also tested for relationships between functional connectivity and motor and cognitive measurements. Group independent component analysis was applied to rs-fMRI data to obtain whole-brain resting state networks. FNC was defined as the correlation between RSN time-courses. Dynamic FNC behavior was captured using a sliding time window approach, and FNC results from each window were assigned to four clusters representing FNC states, using a k-means clustering algorithm. HDgmc individuals spent significantly more time in State-1 (the state with the weakest FNC pattern) compared to HC. However, overall HC individuals showed more FNC dynamism than HDgmc. Significant associations between FNC states and genetic and clinical variables were also identified. In FNC State-4 (the one that most resembled static FNC), HDgmc exhibited significantly decreased connectivity between the putamen and medial prefrontal cortex compared to HC, and this was significantly associated with cognitive performance. In FNC State-1, disease burden in HDgmc participants was significantly associated with connectivity between the postcentral gyrus and posterior cingulate cortex, as well as between the inferior occipital gyrus and posterior parietal cortex.",
+ "publisher": "Human molecular genetics",
+ "issn": "1460-2083",
+ "date": "2014-07-04",
+ "abstract": "Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin (HTT) gene. Disease pathogenesis derives, at least in part, from the long polyglutamine tract encoded by mutant HTT. Therefore, considerable effort has been dedicated to the development of therapeutic strategies that significantly reduce the expression of the mutant HTT protein. Antisense oligonucleotides (ASOs) targeted to the CAG repeat region of HTT transcripts have been of particular interest due to their potential capacity to discriminate between normal and mutant HTT transcripts. Here, we focus on phosphorodiamidate morpholino oligomers (PMOs), ASOs that are especially stable, highly soluble and non-toxic. We designed three PMOs to selectively target expanded CAG repeat tracts (CTG22, CTG25 and CTG28), and two PMOs to selectively target sequences flanking the HTT CAG repeat (HTTex1a and HTTex1b). In HD patient-derived fibroblasts with expanded alleles containing 44, 77 or 109 CAG repeats, HTTex1a and HTTex1b were effective in suppressing the expression of mutant and non-mutant transcripts. CTGn PMOs also suppressed HTT expression, with the extent of suppression and the specificity for mutant transcripts dependent on the length of the targeted CAG repeat and on the CTG repeat length and concentration of the PMO. PMO CTG25 reduced HTT-induced cytotoxicity in vitro and suppressed mutant HTT expression in vivo in the N171-82Q transgenic mouse model. Finally, CTG28 reduced mutant HTT expression and improved the phenotype of Hdh(Q7/Q150) knock-in HD mice. These data demonstrate the potential of PMOs as an approach to suppressing the expression of mutant HTT.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30618191"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25035419"
},
{
- "id": "pmid:30550751",
+ "id": "pmid:25026978",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/30550751",
- "title": "Drp1/Fis1-mediated mitochondrial fragmentation leads to lysosomal dysfunction in cardiac models of Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25026978",
+ "title": "A clinical classification acknowledging neuropsychiatric and cognitive impairment in Huntington's disease.",
"type": "article-journal",
- "doi": "10.1016/j.yjmcc.2018.12.004",
+ "doi": "10.1186/s13023-014-0114-8",
"authors": [
- ["A U", "Joshi"],
- ["A E", "Ebert"],
- ["B", "Haileselassie"],
- ["D", "Mochly-Rosen"]
+ ["Tua", "Vinther-Jensen"],
+ ["Ida U", "Larsen"],
+ ["Lena E", "Hjermind"],
+ ["Esben", "Budtz-J\u00f8rgensen"],
+ ["Troels T", "Nielsen"],
+ ["Anne", "N\u00f8rrem\u00f8lle"],
+ ["J\u00f8rgen E", "Nielsen"],
+ ["Asmus", "Vogel"]
],
- "publisher": "Journal of molecular and cellular cardiology",
- "issn": "1095-8584",
- "date": "2018-12-11",
- "abstract": "Huntington's disease (HD) is a fatal hereditary neurodegenerative disorder, best known for its clinical triad of progressive motor impairment, cognitive deficits and psychiatric disturbances, is caused by CAG-repeat expansion in exon 1 of Huntingtin (HTT). However, in addition to the neurological disease, mutant HTT (mHTT), which is ubiquitously expressed in all tissues, impairs other organ systems. Not surprisingly, cardiovascular dysautonomia as well as the deterioration of circadian rhythms are among the earliest detectable pathophysiological changes in individuals with HD. Mitochondrial dysfunction in the brain and skeletal muscle in HD has been well documented, as the disease progresses. However, not much is known about mitochondrial abnormalities in the heart. In this study, we describe a role for Drp1/Fis1-mediated excessive mitochondrial fission and dysfunction, associated with lysosomal dysfunction in H9C2 expressing long polyglutamine repeat (Q73) and in human iPSC-derived cardiomyocytes transfected with Q77. Expression of long polyglutamine repeat led to reduced ATP production and mitochondrial fragmentation. We observed an increased accumulation of damaged mitochondria in the lysosome that was coupled with lysosomal dysfunction. Importantly, reducing Drp1/Fis1-mediated mitochondrial damage significantly improved mitochondrial function and cell survival. Finally, reducing Fis1-mediated Drp1 recruitment to the mitochondria, using the selective inhibitor of this interaction, P110, improved mitochondrial structure in the cardiac tissue of R6/2 mice. We suggest that drugs focusing on the central nervous system will not address mitochondrial function across all organs, and therefore will not be a sufficient strategy to treat or slow down HD disease progression.",
+ "publisher": "Orphanet journal of rare diseases",
+ "issn": "1750-1172",
+ "date": "2014-07-17",
+ "abstract": "Involuntary movements, neuropsychiatric symptoms, and cognitive impairment are all part of the symptom triad in Huntington's disease (HD). Despite the fact that neuropsychiatric symptoms and cognitive decline may be early manifestations of HD, the clinical diagnosis is conventionally based on the presence of involuntary movements and a positive genetic test for the HD CAG repeat expansion. After investigating the frequencies of the triad manifestations in a large outpatient clinical cohort of HD gene-expansion carriers, we propose a new clinical classification.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30550751"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25026978"
},
{
- "id": "pmid:30354976",
+ "id": "pmid:24938402",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/30354976",
- "title": "Integration of Computed Tomographic Angiography Spot Sign and Noncontrast Computed Tomographic Hypodensities to Predict Hematoma Expansion.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/24938402",
+ "title": "Impaired brain energy metabolism in the BACHD mouse model of Huntington's disease: critical role of astrocyte-neuron interactions.",
"type": "article-journal",
- "doi": "10.1161/strokeaha.118.022010",
+ "doi": "10.1038/jcbfm.2014.110",
"authors": [
- ["Andrea", "Morotti"],
- ["Gregoire", "Boulouis"],
- ["Andreas", "Charidimou"],
- ["Kristin", "Schwab"],
- ["Christina", "Kourkoulis"],
- ["Christopher D", "Anderson"],
- ["M Edip", "Gurol"],
- ["Anand", "Viswanathan"],
- ["Javier M", "Romero"],
- ["Steven M", "Greenberg"],
- ["Jonathan", "Rosand"],
- ["Joshua N", "Goldstein"]
+ ["Lydie", "Boussicault"],
+ ["Anne-Sophie", "H\u00e9rard"],
+ ["Noel", "Calingasan"],
+ ["Fanny", "Petit"],
+ ["Carole", "Malgorn"],
+ ["Nicolas", "Merienne"],
+ ["Caroline", "Jan"],
+ ["Marie-Claude", "Gaillard"],
+ ["Rodrigo", "Lerchundi"],
+ ["Luis F", "Barros"],
+ ["Carole", "Escartin"],
+ ["Thierry", "Delzescaux"],
+ ["Jean", "Mariani"],
+ ["Philippe", "Hantraye"],
+ ["M Flint", "Beal"],
+ ["Emmanuel", "Brouillet"],
+ ["C\u00e9line", "V\u00e9ga"],
+ ["Gilles", "Bonvento"]
],
- "publisher": "Stroke",
- "issn": "1524-4628",
- "date": "2018-09-01",
- "abstract": "Background and Purpose- Noncontrast computed tomographic (CT) hypodensities represent an alternative to the CT angiography spot sign (SS) to predict intracerebral hemorrhage (ICH) expansion. However, previous studies suggested that these markers predicted hematoma expansion independently from each other. We investigated whether the integration of SS and hypodensity (HD) improved the stratification of ICH expansion risk. Methods- A single-center cohort of consecutive patients with ICH was retrospectively analyzed. Patients with available CT angiography, baseline, and follow-up noncontrast CT images available were included. Trained readers reviewed all the images for SS and HD presence, and the study population was classified into 4 groups: SS and HD negative (SS-HD-), SS positive only (SS+HD-), HD positive only (SS-HD+), and SS and HD positive (SS+HD+). ICH expansion was defined as hematoma growth >33% or >6 mL. The association between SS and HD presence and ICH expansion was investigated with multivariable logistic regression. Results- A total of 745 subjects qualified for the analysis (median age, 73 years; 54.1% men). The rates of ICH expansion were 9.3% in SS-HD-, 25.8% in SS+HD-, 27.4% in SS-HD+, and 55.6% in SS+HD+ patients ( P<0.001). After adjustment for potential confounders and keeping SS-HD- subjects as reference, the risk of ICH expansion was increased in SS+HD- and SS-HD+ patients (odds ratio, 2.93, P=0.002 and odds ratio, 3.02, P<0.001, respectively). SS+HD+ subjects had the highest risk of hematoma growth (odds ratio, 9.50; P<0.001). Conclusions- Integration of SS and HD improves the stratification of hematoma growth risk and may help the selection of patients with ICH for antiexpansion treatment in clinical trials.",
+ "publisher": "Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism",
+ "issn": "1559-7016",
+ "date": "2014-06-18",
+ "abstract": "Huntington's disease (HD) is caused by cytosine-adenine-guanine (CAG) repeat expansions in the huntingtin (Htt) gene. Although early energy metabolic alterations in HD are likely to contribute to later neurodegenerative processes, the cellular and molecular mechanisms responsible for these metabolic alterations are not well characterized. Using the BACHD mice that express the full-length mutant huntingtin (mHtt) protein with 97 glutamine repeats, we first demonstrated localized in vivo changes in brain glucose use reminiscent of what is observed in premanifest HD carriers. Using biochemical, molecular, and functional analyses on different primary cell culture models from BACHD mice, we observed that mHtt does not directly affect metabolic activity in a cell autonomous manner. However, coculture of neurons with astrocytes from wild-type or BACHD mice identified mutant astrocytes as a source of adverse non-cell autonomous effects on neuron energy metabolism possibly by increasing oxidative stress. These results suggest that astrocyte-to-neuron signaling is involved in early energy metabolic alterations in HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30354976"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24938402"
},
{
- "id": "pmid:30256717",
+ "id": "pmid:24841383",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/30256717",
- "title": "A patient-derived cellular model for Huntington's disease reveals phenotypes at clinically relevant CAG lengths.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/24841383",
+ "title": "Activation of IGF-1 and insulin signaling pathways ameliorate mitochondrial function and energy metabolism in Huntington's Disease human lymphoblasts.",
"type": "article-journal",
- "doi": "10.1091/mbc.e18-09-0590",
+ "doi": "10.1007/s12035-014-8735-4",
"authors": [
- ["Claudia Lin-Kar", "Hung"],
- ["Tamara", "Maiuri"],
- ["Laura Erin", "Bowie"],
- ["Ryan", "Gotesman"],
- ["Susie", "Son"],
- ["Mina", "Falcone"],
- ["James Victor", "Giordano"],
- ["Tammy", "Gillis"],
- ["Virginia", "Mattis"],
- ["Trevor", "Lau"],
- ["Vickie", "Kwan"],
- ["Vanessa", "Wheeler"],
- ["Jonathan", "Schertzer"],
- ["Karun", "Singh"],
- ["Ray", "Truant"]
+ ["Luana", "Naia"],
+ ["I Lu\u00edsa", "Ferreira"],
+ ["Teresa", "Cunha-Oliveira"],
+ ["Ana I", "Duarte"],
+ ["M\u00e1rcio", "Ribeiro"],
+ ["Tatiana R", "Rosenstock"],
+ ["M\u00e1rio N", "La\u00e7o"],
+ ["Maria J", "Ribeiro"],
+ ["Catarina R", "Oliveira"],
+ ["Fr\u00e9d\u00e9ric", "Saudou"],
+ ["Sandrine", "Humbert"],
+ ["A Cristina", "Rego"]
],
- "publisher": "Molecular biology of the cell",
- "issn": "1939-4586",
- "date": "2018-09-26",
- "abstract": "The huntingtin protein participates in several cellular processes that are disrupted when the polyglutamine tract is expanded beyond a threshold of 37 CAG DNA repeats in Huntington's disease (HD). Cellular biology approaches to understand these functional disruptions in HD have primarily focused on cell lines with synthetically long CAG length alleles that clinically represent outliers in this disease and a more severe form of HD that lacks age onset. Patient-derived fibroblasts are limited to a finite number of passages before succumbing to cellular senescence. We used human telomerase reverse transcriptase (hTERT) to immortalize fibroblasts taken from individuals of varying age, sex, disease onset, and CAG repeat length, which we have termed TruHD cells. TruHD cells display classic HD phenotypes of altered morphology, size and growth rate, increased sensitivity to oxidative stress, aberrant adenosine diphosphate/adenosine triphosphate (ADP/ATP) ratios, and hypophosphorylated huntingtin protein. We additionally observed dysregulated reactive oxygen species (ROS)-dependent huntingtin localization to nuclear speckles in HD cells. We report the generation and characterization of a human, clinically relevant cellular model for investigating disease mechanisms in HD at the single-cell level, which, unlike transformed cell lines, maintains functions critical for huntingtin transcriptional regulation and genomic integrity.",
+ "publisher": "Molecular neurobiology",
+ "issn": "1559-1182",
+ "date": "2014-05-20",
+ "abstract": "Huntington's disease (HD) is an inherited neurodegenerative disease caused by a polyglutamine repeat expansion in the huntingtin protein. Mitochondrial dysfunction associated with energy failure plays an important role in this untreated pathology. In the present work, we used lymphoblasts obtained from HD patients or unaffected parentally related individuals to study the protective role of insulin-like growth factor 1 (IGF-1) versus insulin (at low nM) on signaling and metabolic and mitochondrial functions. Deregulation of intracellular signaling pathways linked to activation of insulin and IGF-1 receptors (IR,IGF-1R), Akt, and ERK was largely restored by IGF-1 and, at a less extent, by insulin in HD human lymphoblasts. Importantly, both neurotrophic factors stimulated huntingtin phosphorylation at Ser421 in HD cells. IGF-1 and insulin also rescued energy levels in HD peripheral cells, as evaluated by increased ATP and phosphocreatine, and decreased lactate levels. Moreover, IGF-1 effectively ameliorated O2 consumption and mitochondrial membrane potential (\u0394\u03c8m) in HD lymphoblasts, which occurred concomitantly with increased levels of cytochrome c. Indeed, constitutive phosphorylation of huntingtin was able to restore the \u0394\u03c8m in lymphoblasts expressing an abnormal expansion of polyglutamines. HD lymphoblasts further exhibited increased intracellular Ca(2+) levels before and after exposure to hydrogen peroxide (H2O2), and decreased mitochondrial Ca(2+) accumulation, being the later recovered by IGF-1 and insulin in HD lymphoblasts pre-exposed to H2O2. In summary, the data support an important role for IR/IGF-1R mediated activation of signaling pathways and improved mitochondrial and metabolic function in HD human lymphoblasts.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30256717"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24841383"
},
{
- "id": "pmid:30171891",
+ "id": "pmid:24825316",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/30171891",
- "title": "Mutational analysis implicates the amyloid fibril as the toxic entity in Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/24825316",
+ "title": "High stress hormone levels accelerate the onset of memory deficits in male Huntington's disease mice.",
"type": "article-journal",
- "doi": "10.1016/j.nbd.2018.08.019",
+ "doi": "10.1016/j.nbd.2014.05.004",
"authors": [
- ["Kenneth W", "Drombosky"],
- ["Sascha", "Rode"],
- ["Ravi", "Kodali"],
- ["Tija C", "Jacob"],
- ["Michael J", "Palladino"],
- ["Ronald", "Wetzel"]
+ ["Christina", "Mo"],
+ ["Terence Y", "Pang"],
+ ["Mark I", "Ransome"],
+ ["Rachel A", "Hill"],
+ ["Thibault", "Renoir"],
+ ["Anthony J", "Hannan"]
],
"publisher": "Neurobiology of disease",
"issn": "1095-953X",
- "date": "2018-08-30",
- "abstract": "In Huntington disease (HD), an expanded polyglutamine (polyQ\u202f>\u202f37) sequence within huntingtin (htt) exon1 leads to enhanced disease risk. It has proved difficult, however, to determine whether the toxic form generated by polyQ expansion is a misfolded or avid-binding monomer, an \u03b1-helix-rich oligomer, or a \u03b2-sheet-rich amyloid fibril. Here we describe an engineered htt exon1 analog featuring a short polyQ sequence that nonetheless quickly forms amyloid fibrils and causes HD-like toxicity in rat neurons and Drosophila. Additional modifications within the polyQ segment produce htt exon1 analogs that populate only spherical oligomers and are non-toxic in cells and flies. Furthermore, in mixture with expanded-polyQ htt exon1, the latter analogs in vitro suppress amyloid formation and promote oligomer formation, and in vivo rescue neurons and flies expressing mhtt exon1 from dysfunction and death. Thus, in our experiments, while htt exon1 toxicity tracks with aggregation propensity, it does so in spite of the toxic construct's possessing polyQ tracts well below those normally considered to be disease-associated. That is, aggregation propensity proves to be a more accurate surrogate for toxicity than is polyQ repeat length itself, strongly supporting a major toxic role for htt exon1 aggregation in HD. In addition, the results suggest that the aggregates that are most toxic in these model systems are amyloid-related. These engineered analogs are novel tools for mapping properties of polyQ self-assembly intermediates and products that should similarly be useful in the analysis of other expanded polyQ diseases. Small molecules with similar amyloid inhibitory properties might be developed into effective therapeutic agents.",
- "language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30171891"
-},
-{
- "id": "pmid:30138645",
- "manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/30138645",
- "title": "Genetic association analyses and meta-analysis of Dynorphin-Kappa Opioid system potential functional variants with heroin dependence.",
- "type": "article-journal",
- "doi": "10.1016/j.neulet.2018.08.023",
- "authors": [
- ["Ji", "Yuanyuan"],
- ["Su", "Rui"],
- ["Tang", "Hua"],
- ["Cui", "Jingjing"],
- ["Deji", "Cuola"],
- ["Shi", "Yuhui"],
- ["Wei", "Shuguang"]
- ],
- "publisher": "Neuroscience letters",
- "issn": "1872-7972",
- "date": "2018-08-20",
- "abstract": "Prodynorphin (PDYN) binds to k-opioid receptors (KOPr; encoded by OPRK1) and is known to regulate dopaminergic tone, making this system important for drugs addiction. Dynorphin (Dyn)/KORr system are powerful effectors of stress-induced alterations in reward processing and dysphoric states. Thus, We identified 11 potential functional SNPs and one variable number of tandem repeat (VNTR) in this system, performed a case-control association analysis, investigated particular disease phenotypes, assessed the joint effect of variants in two genes, carried out a meta-analysis to analyze the association between this VNTR and Heroin dependence (HD) risk. Eleven single-nucleotide polymorphisms (SNPs) were genotyped using SNaPshot SNP technology. Participants included 566 healthy controls and 541 patients with HD. We found that PDYN polymorphisms modulate the susceptibility to HD. An increased risk of HD was significantly associated with H alleles of PDYN VNTR (\u03c7",
+ "date": "2014-05-10",
+ "abstract": "Huntington's disease (HD) is a neurodegenerative disorder caused by a tandem repeat mutation in the huntingtin gene. Lifestyle factors, such as lack of activity may contribute to the variability in the age of disease onset. Therefore, better understanding of environmental modifiers may uncover potential therapeutic approaches to delay disease onset and progression. Recent data suggest that HD patients and transgenic mouse models show a dysregulated stress response. In this present study, we elevated stress hormone levels through oral corticosterone (CORT) treatment and assessed its impact on the development of motor impairment and cognitive deficits using the R6/1 transgenic mouse model of HD. We found that CORT consumption did not alter rotarod performance of R6/1 HD or wild-type (WT) littermates. However, the onset of hippocampal-dependent Y-maze deficits was accelerated in male R6/1 mice by 5days of CORT treatment, whereas short term memory of WT and female R6/1 mice was unaffected. We then further investigated the male HD susceptibility to CORT by measuring TrkB activation, BDNF and glucocorticoid receptor expression as well as the level of cell proliferation in the hippocampus. CORT treatment increased the levels of phosphorylated TrkB in male R6/1 mice only. There were no effects of CORT on hippocampal BDNF protein or mRNA levels; nor on expression of the glucocorticoid receptors in any group. Hippocampal cell proliferation was decreased in male R6/1 mice and this was further reduced in CORT-drinking male R6/1 mice. Female mice (WT and R6/1) appeared to be protected from the impacts of CORT treatment in all our hippocampal measures. Overall, our data demonstrate that treatment with corticosterone is able to modulate the onset of HD symptomatology. We present the first evidence of a male-specific vulnerability to stress impacting on the development of short-term memory deficits in HD. More generally, we found that female mice were protected from the detrimental effects of CORT treatment on a variety of hippocampus-based measures. Hippocampal plasticity and memory in HD may be more susceptible to the impacts of stress in a sex-dependent manner. We propose clinical investigations of stress as a key environmental modifier of HD symptom onset.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30138645"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24825316"
},
{
- "id": "pmid:30103338",
+ "id": "pmid:24784230",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/30103338",
- "title": "Reduced Cancer Incidence in Huntington's Disease: Analysis in the Registry Study.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/24784230",
+ "title": "Neuronal targets for reducing mutant huntingtin expression to ameliorate disease in a mouse model of Huntington's disease.",
"type": "article-journal",
- "doi": "10.3233/jhd-170263",
+ "doi": "10.1038/nm.3514",
"authors": [
- ["Paul", "McNulty"],
- ["Richard", "Pilcher"],
- ["Raviram", "Ramesh"],
- ["Renata", "Necuiniate"],
- ["Alis", "Hughes"],
- ["Daniel", "Farewell"],
- ["Peter", "Holmans"],
- ["Lesley", "Jones"]
+ ["Nan", "Wang"],
+ ["Michelle", "Gray"],
+ ["Xiao-Hong", "Lu"],
+ ["Jeffrey P", "Cantle"],
+ ["Sandra M", "Holley"],
+ ["Erin", "Greiner"],
+ ["Xiaofeng", "Gu"],
+ ["Dyna", "Shirasaki"],
+ ["Carlos", "Cepeda"],
+ ["Yuqing", "Li"],
+ ["Hongwei", "Dong"],
+ ["Michael S", "Levine"],
+ ["X William", "Yang"]
],
- "publisher": "Journal of Huntington's disease",
- "issn": "1879-6400",
- "date": "2018-01-01",
- "abstract": "People with Huntington's disease (HD) have been observed to have lower rates of cancers.",
+ "publisher": "Nature medicine",
+ "issn": "1546-170X",
+ "date": "2014-04-28",
+ "abstract": "Huntington's disease (HD) is a fatal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion leading to an elongated polyglutamine stretch in huntingtin. Mutant huntingtin (mHTT) is ubiquitously expressed in all cells but elicits selective cortical and striatal neurodegeneration in HD. The mechanistic basis for such selective neuronal vulnerability remains unclear. A necessary step toward resolving this enigma is to define the cell types in which mHTT expression is causally linked to the disease pathogenesis. Using a conditional transgenic mouse model of HD, in which the mice express full-length human mHTT from a bacterial artificial chromosome transgene (BACHD), we genetically reduced mHTT expression in neuronal populations in the striatum, cortex or both. We show that reduction of cortical mHTT expression in BACHD mice partially improves motor and psychiatric-like behavioral deficits but does not improve neurodegeneration, whereas reduction of mHTT expression in both neuronal populations consistently ameliorates all behavioral deficits and selective brain atrophy in this HD model. Furthermore, whereas reduction of mHTT expression in cortical or striatal neurons partially ameliorates corticostriatal synaptic deficits, further restoration of striatal synaptic function can be achieved by reduction of mHTT expression in both neuronal cell types. Our study demonstrates distinct but interacting roles of cortical and striatal mHTT in HD pathogenesis and suggests that optimal HD therapeutics may require targeting mHTT in both cortical and striatal neurons.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30103338"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24784230"
},
{
- "id": "pmid:30007561",
+ "id": "pmid:24706734",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/30007561",
- "title": "AAV5-miHTT Gene Therapy Demonstrates Broad Distribution and Strong Human Mutant Huntingtin Lowering in a Huntington's Disease Minipig Model.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/24706734",
+ "title": "The Corticospinal Tract in Huntington's Disease.",
"type": "article-journal",
- "doi": "10.1016/j.ymthe.2018.06.021",
+ "doi": "10.1093/cercor/bhu065",
"authors": [
- ["Melvin M", "Evers"],
- ["Jana", "Miniarikova"],
- ["Stefan", "Juhas"],
- ["Astrid", "Vall\u00e8s"],
- ["Bozena", "Bohuslavova"],
- ["Jana", "Juhasova"],
- ["Helena Kupcova", "Skalnikova"],
- ["Petr", "Vodicka"],
- ["Ivona", "Valekova"],
- ["Cynthia", "Brouwers"],
- ["Bas", "Blits"],
- ["Jacek", "Lubelski"],
- ["Hana", "Kovarova"],
- ["Zdenka", "Ellederova"],
- ["Sander J", "van Deventer"],
- ["Harald", "Petry"],
- ["Jan", "Motlik"],
- ["Pavlina", "Konstantinova"]
+ ["O", "Phillips"],
+ ["F", "Squitieri"],
+ ["C", "Sanchez-Castaneda"],
+ ["F", "Elifani"],
+ ["A", "Griguoli"],
+ ["V", "Maglione"],
+ ["C", "Caltagirone"],
+ ["U", "Sabatini"],
+ ["M", "Di Paola"]
],
- "publisher": "Molecular therapy : the journal of the American Society of Gene Therapy",
- "issn": "1525-0024",
- "date": "2018-06-25",
- "abstract": "Huntington's disease (HD) is a fatal neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin gene. Previously, we showed strong huntingtin reduction and prevention of neuronal dysfunction in HD rodents using an engineered microRNA targeting human huntingtin, delivered via adeno-associated virus (AAV) serotype 5 vector with a transgene encoding an engineered miRNA against HTT mRNA (AAV5-miHTT). One of the challenges of rodents as a model of neurodegenerative diseases is their relatively small brain, making successful translation to the HD patient difficult. This is particularly relevant for gene therapy approaches, where distribution achieved upon local administration into the parenchyma is likely dependent on brain size and structure. Here, we aimed to demonstrate the translation of huntingtin-lowering gene therapy to a large-animal brain. We investigated the feasibility, efficacy, and tolerability of one-time intracranial administration of AAV5-miHTT in the transgenic HD (tgHD) minipig model. We detected widespread dose-dependent distribution of AAV5-miHTT throughout the tgHD minipig brain that correlated with the engineered microRNA expression. Both human mutant huntingtin mRNA and protein were significantly reduced in all brain regions transduced by AAV5-miHTT. The combination of widespread vector distribution and extensive huntingtin lowering observed with AAV5-miHTT supports the translation of a huntingtin-lowering gene therapy for HD from preclinical studies into the clinic.",
+ "publisher": "Cerebral cortex (New York, N.Y. : 1991)",
+ "issn": "1460-2199",
+ "date": "2014-04-04",
+ "abstract": "Huntington's disease (HD) is characterized by progressive motor impairment. Therefore, the connectivity of the corticospinal tract (CST), which is the main white matter (WM) pathway that conducts motor impulses from the primary motor cortex to the spinal cord, merits particular attention. WM abnormalities have already been shown in presymptomatic (Pre-HD) and symptomatic HD subjects using magnetic resonance imaging (MRI). In the present study, we examined CST microstructure using diffusion tensor imaging (DTI)-based tractography in 30-direction DTI data collected from 100 subjects: Pre-HD subjects (n = 25), HD patients (n = 25) and control subjects (n = 50), and T2*-weighted (iron sensitive) imaging. Results show decreased fractional anisotropy (FA) and increased axial (AD), and radial diffusivity (RD) in the bilateral CST of HD patients. Pre-HD subjects had elevated iron in the left CST, regionally localized between the brainstem and thalamus. CAG repeat length in conjunction with age, as well as motor (UHDRS) assessment were correlated with CST FA, AD, and RD both in Pre-HD and HD. In the presymptomatic phase, increased iron in the inferior portion supports the \"dying back\" hypothesis that axonal damage advances in a retrograde fashion. Furthermore, early iron alteration may cause a high level of toxicity, which may contribute to further damage.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30007561"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24706734"
},
{
- "id": "pmid:29902468",
+ "id": "pmid:24633813",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/29902468",
- "title": "Intravenous immunoglobulin ameliorates motor and cognitive deficits and neuropathology in R6/2 mouse model of Huntington's disease by decreasing mutant huntingtin protein level and normalizing NF-\u03baB signaling pathway.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/24633813",
+ "title": "Mitochondrial membrane fluidity is consistently increased in different models of Huntington disease: restorative effects of olesoxime.",
"type": "article-journal",
- "doi": "10.1016/j.brainres.2018.06.009",
+ "doi": "10.1007/s12035-014-8663-3",
"authors": [
- ["Shu-Ying", "Liu"],
- ["Xiao-Lin", "Yu"],
- ["Jie", "Zhu"],
- ["Xiang-Meng", "Liu"],
- ["Yue", "Zhang"],
- ["Quan-Xiu", "Dong"],
- ["Shan", "Ma"],
- ["Rui-Tian", "Liu"]
+ ["Janett", "Eckmann"],
+ ["Laura E", "Clemens"],
+ ["Schamim H", "Eckert"],
+ ["Stephanie", "Hagl"],
+ ["Libo", "Yu-Taeger"],
+ ["Thierry", "Bordet"],
+ ["Rebecca M", "Pruss"],
+ ["Walter E", "Muller"],
+ ["Kristina", "Leuner"],
+ ["Huu P", "Nguyen"],
+ ["Gunter P", "Eckert"]
],
- "publisher": "Brain research",
- "issn": "1872-6240",
- "date": "2018-06-11",
- "abstract": "Huntington's disease (HD) is a fatal neurodegenerative disorder characterized by progressive movement disorders and cognitive deficits, which is caused by a CAG-repeat expansion encoding an extended polyglutamine (polyQ) tract in the huntingtin protein (HTT). Reduction of mutant HTT levels and inhibition of neuroinflammation has been proposed as a major therapeutic strategy in treating HD. Intravenous immunoglobulin (IVIg) therapy has been firmly established for the treatment of several autoimmune or inflammatory neurological diseases, either as adjunctive treatment or as first-line therapy. However, whether IVIg has therapeutic potential on HD remains unclear. Here we for the first time demonstrated that IVIg treatment remarkably rescued motor and cognitive deficits, prevented synaptic degeneration, attenuated neuroinflammation and oxidative stress in R6/2 mouse model. Further investigation showed that the beneficial effects of IVIg resulted from the reduced levels of mutant HTT and inhibition of NF-\u03baB signalling pathway. These findings suggest that IVIg is a promising therapeutic potential for HD.",
+ "publisher": "Molecular neurobiology",
+ "issn": "1559-1182",
+ "date": "2014-03-18",
+ "abstract": "Huntington disease (HD) is a fatal neurodegenerative disorder caused by a CAG repeat expansion in exon 1 of the huntingtin gene (HTT). One prominent target of the mutant huntingtin protein (mhtt) is the mitochondrion, affecting its morphology, distribution, and function. Thus, mitochondria have been suggested as potential therapeutic targets for the treatment of HD. Olesoxime, a cholesterol-like compound, promotes motor neuron survival and neurite outgrowth in vitro, and its effects are presumed to occur via a direct interaction with mitochondrial membranes (MMs). We examined the properties of MMs isolated from cell and animal models of HD as well as the effects of olesoxime on MM fluidity and cholesterol levels. MMs isolated from brains of aged Hdh Q111/Q111 knock-in mice showed a significant decrease in 1,6-diphenyl-hexatriene (DPH) anisotropy, which is inversely correlated with membrane fluidity. Similar increases in MM fluidity were observed in striatal STHdh Q111/Q111 cells as well as in MMs isolated from brains of BACHD transgenic rats. Treatment of STHdh cells with olesoxime decreased the fluidity of isolated MMs. Decreased membrane fluidity was also measured in olesoxime-treated MMs isolated from brains of HD knock-in mice. In both models, treatment with olesoxime restored HD-specific changes in MMs. Accordingly, olesoxime significantly counteracted the mhtt-induced increase in MM fluidity of MMs isolated from brains of BACHD rats after 12 months of treatment in vivo, possibly by enhancing MM cholesterol levels. Thus, olesoxime may represent a novel pharmacological tool to treat mitochondrial dysfunction in HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29902468"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24633813"
},
{
- "id": "pmid:29813067",
+ "id": "pmid:24465260",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/29813067",
- "title": "Spontaneous gain of susceptibility suggests a novel mechanism of resistance to hybrid dysgenesis in Drosophila virilis.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/24465260",
+ "title": "CAG-Expansion Haplotype Analysis in a Population with a Low Prevalence of Huntington's Disease.",
"type": "article-journal",
- "doi": "10.1371/journal.pgen.1007400",
+ "doi": "10.3988/jcn.2014.10.1.32",
"authors": [
- ["Sergei Y", "Funikov"],
- ["Dina A", "Kulikova"],
- ["George S", "Krasnov"],
- ["Alexander P", "Rezvykh"],
- ["Lubov N", "Chuvakova"],
- ["Natalia G", "Shostak"],
- ["Elena S", "Zelentsova"],
- ["Justin P", "Blumenstiel"],
- ["Michael B", "Evgen'ev"]
+ ["Teeratorn", "Pulkes"],
+ ["Chutima", "Papsing"],
+ ["Sukanya", "Wattanapokayakit"],
+ ["Surakameth", "Mahasirimongkol"]
],
- "publisher": "PLoS genetics",
- "issn": "1553-7404",
- "date": "2018-05-29",
- "abstract": "Syndromes of hybrid dysgenesis (HD) have been critical for our understanding of the transgenerational maintenance of genome stability by piRNA. HD in D. virilis represents a special case of HD since it includes simultaneous mobilization of a set of TEs that belong to different classes. The standard explanation for HD is that eggs of the responder strains lack an abundant pool of piRNAs corresponding to the asymmetric TE families transmitted solely by sperm. However, there are several strains of D. virilis that lack asymmetric TEs, but exhibit a \"neutral\" cytotype that confers resistance to HD. To characterize the mechanism of resistance to HD, we performed a comparative analysis of the landscape of ovarian small RNAs in strains that vary in their resistance to HD mediated sterility. We demonstrate that resistance to HD cannot be solely explained by a maternal piRNA pool that matches the assemblage of TEs that likely cause HD. In support of this, we have witnessed a cytotype shift from neutral (N) to susceptible (M) in a strain devoid of all major TEs implicated in HD. This shift occurred in the absence of significant change in TE copy number and expression of piRNAs homologous to asymmetric TEs. Instead, this shift is associated with a change in the chromatin profile of repeat sequences unlikely to be causative of paternal induction. Overall, our data suggest that resistance to TE-mediated sterility during HD may be achieved by mechanisms that are distinct from the canonical syndromes of HD.",
+ "publisher": "Journal of clinical neurology (Seoul, Korea)",
+ "issn": "1738-6586",
+ "date": "2014-01-06",
+ "abstract": "The prevalence of Huntington's disease (HD) among East Asians is less than one-tenth of that among Caucasians. Such a low prevalence may be attributable to a lack of carriers of specific predisposing haplogroups associated with the high instability of the Huntingtin gene (HTT). The aim of this study was to evaluate the association between specific HTT haplogroups and the occurrence of HD in a Thai population.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29813067"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24465260"
},
{
- "id": "pmid:29685790",
+ "id": "pmid:24459107",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/29685790",
- "title": "Effect of Trinucleotide Repeats in the Huntington's Gene on Intelligence.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/24459107",
+ "title": "HTT-lowering reverses Huntington's disease immune dysfunction caused by NF\u03baB pathway dysregulation.",
"type": "article-journal",
- "doi": "10.1016/j.ebiom.2018.03.031",
+ "doi": "10.1093/brain/awt355",
"authors": [
- ["Jessica K", "Lee"],
- ["Amy", "Conrad"],
- ["Eric", "Epping"],
- ["Kathy", "Mathews"],
- ["Vincent", "Magnotta"],
- ["Jeffrey D", "Dawson"],
- ["Peg", "Nopoulos"]
+ ["Ulrike", "Tr\u00e4ger"],
+ ["Ralph", "Andre"],
+ ["Nayana", "Lahiri"],
+ ["Anna", "Magnusson-Lind"],
+ ["Andreas", "Weiss"],
+ ["Stephan", "Grueninger"],
+ ["Chris", "McKinnon"],
+ ["Eva", "Sirinathsinghji"],
+ ["Shira", "Kahlon"],
+ ["Edith L", "Pfister"],
+ ["Roger", "Moser"],
+ ["Holger", "Hummerich"],
+ ["Michael", "Antoniou"],
+ ["Gillian P", "Bates"],
+ ["Ruth", "Luthi-Carter"],
+ ["Mark W", "Lowdell"],
+ ["Maria", "Bj\u00f6rkqvist"],
+ ["Gary R", "Ostroff"],
+ ["Neil", "Aronin"],
+ ["Sarah J", "Tabrizi"]
],
- "publisher": "EBioMedicine",
- "issn": "2352-3964",
- "date": "2018-03-30",
- "abstract": "Huntington's Disease (HD) is caused by an abnormality in the HTT gene. This gene includes trinucleotide repeats ranging from 10 to 35, and when expanded beyond 39, causes HD. We previously reported that CAG repeats in the normal range had a direct and beneficial effect on brain development with higher repeats being associated with higher cognitive function. The current study now expands this line of inquiry to evaluate the effects of CAG repeat throughout the entire spectrum of repeats from 15 to 58.",
+ "publisher": "Brain : a journal of neurology",
+ "issn": "1460-2156",
+ "date": "2014-01-22",
+ "abstract": "Huntington's disease is an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. The peripheral innate immune system contributes to Huntington's disease pathogenesis and has been targeted successfully to modulate disease progression, but mechanistic understanding relating this to mutant huntingtin expression in immune cells has been lacking. Here we demonstrate that human Huntington's disease myeloid cells produce excessive inflammatory cytokines as a result of the cell-intrinsic effects of mutant huntingtin expression. A direct effect of mutant huntingtin on the NF\u03baB pathway, whereby it interacts with IKK\u03b3, leads to increased degradation of I\u03baB and subsequent nuclear translocation of RelA. Transcriptional alterations in intracellular immune signalling pathways are also observed. Using a novel method of small interfering RNA delivery to lower huntingtin expression, we show reversal of disease-associated alterations in cellular function-the first time this has been demonstrated in primary human cells. Glucan-encapsulated small interfering RNA particles were used to lower huntingtin levels in human Huntington's disease monocytes/macrophages, resulting in a reversal of huntingtin-induced elevated cytokine production and transcriptional changes. These findings improve our understanding of the role of innate immunity in neurodegeneration, introduce glucan-encapsulated small interfering RNA particles as tool for studying cellular pathogenesis ex vivo in human cells and raise the prospect of immune cell-directed HTT-lowering as a therapeutic in Huntington's disease.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29685790"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24459107"
},
{
- "id": "pmid:29670796",
+ "id": "pmid:24452335",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/29670796",
- "title": "Huntington's Disease in a Patient Misdiagnosed as Conversion Disorder.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/24452335",
+ "title": "Copy-number variation of the neuronal glucose transporter gene SLC2A3 and age of onset in Huntington's disease.",
"type": "article-journal",
- "doi": "10.1155/2018/3915657",
+ "doi": "10.1093/hmg/ddu022",
"authors": [
- ["Jo\u00e3o Machado", "Nogueira"],
- ["Ana Margarida", "Franco"],
- ["Susana", "Mendes"],
- ["Anabela", "Valadas"],
- ["Cristina", "Semedo"],
- ["Gustavo", "Jesus"]
+ ["Angelica", "Vittori"],
+ ["Carlo", "Breda"],
+ ["Mariaelena", "Repici"],
+ ["Michael", "Orth"],
+ ["Raymund A C", "Roos"],
+ ["Tiago F", "Outeiro"],
+ ["Flaviano", "Giorgini"],
+ ["Edward J", "Hollox"]
],
- "publisher": "Case reports in psychiatry",
- "issn": "2090-682X",
- "date": "2018-02-18",
- "abstract": "Huntington's disease (HD) is an inherited, progressive, and neurodegenerative neuropsychiatric disorder caused by the expansion of cytosine-adenine-guanine (CAG) trinucleotide in Interested Transcript (IT) 15 gene on chromosome 4. This pathology typically presents in individuals aged between 30 and 50 years and the age of onset is inversely correlated with the length of the CAG repeat expansion. It is characterized by chorea, cognitive deficits, and psychiatric symptoms. Usually the psychiatric disorders precede motor and cognitive impairment, Major Depressive Disorder and anxiety disorders being the most common presentations. We present a clinical case of a 65-year-old woman admitted to our Psychiatric Acute Unit. During the 6 years preceding the admission, the patient had clinical assessments made several times by different specialties that focused only on isolated symptoms, disregarding the syndrome as a whole. In the course of her last admission, the patient was referred to our Neuropsychiatric Team, which made the provisional diagnosis of late-onset Huntington's disease, later confirmed by genetic testing. This clinical vignette highlights the importance of a multidisciplinary approach to atypical clinical presentations and raises awareness for the relevance of investigating carefully motor symptoms in psychiatric patients.",
+ "publisher": "Human molecular genetics",
+ "issn": "1460-2083",
+ "date": "2014-01-22",
+ "abstract": "Huntington's disease (HD) is a devastating neurodegenerative disorder which is inherited in an autosomal dominant manner. HD is caused by a trinucleotide CAG repeat expansion that encodes a polyglutamine stretch in the huntingtin (HTT) protein. Mutant HTT expression leads to a myriad of cellular dysfunctions culminating in neuronal loss and consequent motor, cognitive and psychiatric disturbances in HD patients. The length of the CAG repeat is inversely correlated with age of onset (AO) in HD patients, while environmental and genetic factors can further modulate this parameter. Here, we explored whether the recently described copy-number variation (CNV) of the gene SLC2A3-which encodes the neuronal glucose transporter GLUT3-could modulate AO in HD. Strikingly, we found that increased dosage of SLC2A3 delayed AO in an HD cohort of 987 individuals, and that this correlated with increased levels of GLUT3 in HD patient cells. To our knowledge this is the first time that CNV of a candidate gene has been found to modulate HD pathogenesis. Furthermore, we found that increasing dosage of Glut1-the Drosophila melanogaster homologue of this glucose transporter-ameliorated HD-relevant phenotypes in fruit flies, including neurodegeneration and life expectancy. As alterations in glucose metabolism have been implicated in HD pathogenesis, this study may have important therapeutic relevance for HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29670796"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24452335"
},
{
- "id": "pmid:29535594",
+ "id": "pmid:24390280",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/29535594",
- "title": "Precise Excision of the CAG Tract from the Huntingtin Gene by Cas9 Nickases.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/24390280",
+ "title": "Intrajugular vein delivery of AAV9-RNAi prevents neuropathological changes and weight loss in Huntington's disease mice.",
"type": "article-journal",
- "doi": "10.3389/fnins.2018.00075",
+ "doi": "10.1038/mt.2013.289",
"authors": [
- ["Magdalena", "Dabrowska"],
- ["Wojciech", "Juzwa"],
- ["Wlodzimierz J", "Krzyzosiak"],
- ["Marta", "Olejniczak"]
+ ["Brett D", "Dufour"],
+ ["Catherine A", "Smith"],
+ ["Randall L", "Clark"],
+ ["Timothy R", "Walker"],
+ ["Jodi L", "McBride"]
],
- "publisher": "Frontiers in neuroscience",
- "issn": "1662-4548",
- "date": "2018-02-26",
- "abstract": "Huntington's disease (HD) is a progressive autosomal dominant neurodegenerative disorder caused by the expansion of CAG repeats in the first exon of the huntingtin gene (",
+ "publisher": "Molecular therapy : the journal of the American Society of Gene Therapy",
+ "issn": "1525-0024",
+ "date": "2014-01-06",
+ "abstract": "Huntington's disease (HD) is a fatal neurological disorder caused by a CAG repeat expansion in the HTT gene, which encodes a mutant huntingtin protein (mHTT). The mutation confers a toxic gain of function on huntingtin, leading to widespread neurodegeneration and inclusion formation in many brain regions. Although the hallmark symptom of HD is hyperkinesia stemming from striatal degeneration, several other brain regions are affected which cause psychiatric, cognitive, and metabolic symptoms. Additionally, mHTT expression in peripheral tissue is associated with skeletal muscle atrophy, cardiac failure, weight loss, and diabetes. We, and others, have demonstrated a prevention of motor symptoms in HD mice following direct striatal injection of adeno-associated viral vector (AAV) serotype 1 encoding an RNA interference (RNAi) construct targeting mutant HTT mRNA (mHTT). Here, we expand these efforts and demonstrate that an intrajugular vein injection of AAV serotype 9 (AAV9) expressing a mutant HTT-specific RNAi construct significantly reduced mHTT expression in multiple brain regions and peripheral tissues affected in HD. Correspondingly, this approach prevented atrophy and inclusion formation in key brain regions as well as the severe weight loss germane to HD transgenic mice. These results demonstrate that systemic delivery of AAV9-RNAi may provide more widespread clinical benefit for patients suffering from HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29535594"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24390280"
},
{
- "id": "pmid:29494703",
+ "id": "pmid:24359926",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/29494703",
- "title": "Premanifest Huntington's disease: Examination of oculomotor abnormalities in clinical practice.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/24359926",
+ "title": "Nucleotide excision repair and the 26S proteasome function together to promote trinucleotide repeat expansions.",
"type": "article-journal",
- "doi": "10.1371/journal.pone.0193866",
+ "doi": "10.1016/j.dnarep.2013.11.004",
"authors": [
- ["Jessica Y", "Winder"],
- ["Raymund A C", "Roos"]
+ ["Claire", "Concannon"],
+ ["Robert S", "Lahue"]
],
- "publisher": "PloS one",
- "issn": "1932-6203",
- "date": "2018-03-01",
- "abstract": "Different oculomotor abnormalities have been reported to occur in premanifest Huntington's disease. The aim of this study is to investigate which oculomotor items of the Unified Huntington's Disease Rating Scale (UHDRS) are affected in premanifest individuals compared to healthy controls, and if CAG repeat length and age are correlated with oculomotor abnormalities in premanifest Huntington's disease gene carriers.",
+ "publisher": "DNA repair",
+ "issn": "1568-7856",
+ "date": "2013-12-17",
+ "abstract": "Trinucleotide repeat (TNR) expansion underpins a number of inheritable neurological human disorders. Multiple mechanisms are thought to contribute to the expansion process. The incorrect processing of the repeat tract by DNA repair proteins can drive this mutation process forward, as expansions are suppressed following ablation of certain repair factors in mouse models and cell models of disease. Nucleotide excision repair (NER) is one repair pathway implicated in TNR instability, although most previous work focussed on TNR contractions, not expansions. Here we investigated the role of NER in modulating expansions of threshold-length (CTG\u00b7CAG) repeats in yeast. We show that both the global genome and transcription-coupled repair subpathways promote expansions of threshold-length TNRs. Furthermore, NER works with the 26S proteasome to drive expansions, based on analysis of double mutants defective in both pathways, and of Rad23, a protein involved in both NER and the shuttling of ubiquitinated proteins to the proteasome. This work provides the first evidence that both subpathways of NER can promote threshold-length TNR expansions and that NER interacts with the proteasome to drive expansions.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29494703"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24359926"
},
{
- "id": "pmid:29480204",
+ "id": "pmid:24314096",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/29480204",
- "title": "Early Neurodegeneration in R6/2 Mice Carrying the Huntington's Disease Mutation with a Super-Expanded CAG Repeat, Despite Normal Lifespan.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/24314096",
+ "title": "Clinical and genetic features of Huntington disease in Sri Lanka.",
"type": "article-journal",
- "doi": "10.3233/jhd-170265",
+ "doi": "10.1186/1471-2377-13-191",
"authors": [
- ["Catherine", "Kielar"],
- ["A Jennifer", "Morton"]
+ ["Dulika S", "Sumathipala"],
+ ["Rohan W", "Jayasekara"],
+ ["Vajira H W", "Dissanayake"]
],
- "publisher": "Journal of Huntington's disease",
- "issn": "1879-6400",
- "date": "2018-01-01",
- "abstract": "The threshold of CAG repeat expansion in the HTT gene that causes HD is 36 CAG repeats, although 'superlong' expansions are found in individual neurons in postmortem brains. Previously, we showed that, compared to mice with <250 CAG repeats, onset of disease in R6/2 mice carrying superlong (>440) CAG repeat expansions was delayed, and disease progression was slower. Inclusion pathology also differed from 250 CAG repeat mice, being dominated by a novel kind of extranuclear neuronal inclusion (nENNI) that resembles a class of aggregate seen in patients with the adult onset form of HD. Here, we characterised neuropathology in R6/2 mice with >400 CAG repeats using light and electron microscopy. nENNIs were found with increased frequency and wider distribution with age. Some nENNIs appear to 'mature' as the disease develops, developing a multi-layered cored structure. Mice with superlong CAG repeats do not develop clinical signs until they are around 30-40 weeks of age, and they attain a normal life span (>2 years). Nevertheless, they show brain atrophy and unequivocal neuron loss from the striatum and cortex by 22 weeks of age, an age at which similar pathology is seen in 250 CAG repeat mice. Since this time-point is 'end stage' for a 250 CAG mouse, but very far (at least 18 months) from end stage for a\u200a> \u200a440 CAG repeat mouse, our data confirm that the appearance of clinical signs, the formation of inclusions, and neurodegeneration are processes that progress independently. A better understanding of the relationship between CAG repeat length, neurodegenerative pathways, and clinical behavioural signs is essential, if we are to find strategies to delay or reverse the course of this disease.",
+ "publisher": "BMC neurology",
+ "issn": "1471-2377",
+ "date": "2013-12-05",
+ "abstract": "Huntington disease was one of the first neurological hereditary diseases for which genetic testing was made possible as early as 1993. The study describes the clinical and genetic characteristics of patients with Huntington disease in Sri Lanka.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29480204"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24314096"
},
{
- "id": "pmid:29462355",
+ "id": "pmid:24286237",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/29462355",
- "title": "Small molecule modulator of protein disulfide isomerase attenuates mutant huntingtin toxicity and inhibits endoplasmic reticulum stress in a mouse model of Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/24286237",
+ "title": "Genetic variation in the monoamine oxidase A and serotonin transporter genes in sudden infant death syndrome.",
"type": "article-journal",
- "doi": "10.1093/hmg/ddy061",
+ "doi": "10.1111/apa.12526",
"authors": [
- ["Xiao", "Zhou"],
- ["Gang", "Li"],
- ["Anna", "Kaplan"],
- ["Michael M", "Gaschler"],
- ["Xiaoyan", "Zhang"],
- ["Zhipeng", "Hou"],
- ["Mali", "Jiang"],
- ["Roseann", "Zott"],
- ["Serge", "Cremers"],
- ["Brent R", "Stockwell"],
- ["Wenzhen", "Duan"]
+ ["Siri H", "Opdal"],
+ ["\u00c5shild", "Vege"],
+ ["Torleiv O", "Rognum"]
],
- "publisher": "Human molecular genetics",
- "issn": "1460-2083",
- "date": "2018-05-01",
- "abstract": "Huntington's disease (HD) is caused by a cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the huntingtin (HTT) gene encoding an elongated polyglutamine tract within the N-terminal of the huntingtin protein (Htt) and leads to Htt misfolding, aberrant protein aggregation, and progressive appearance of disease symptoms. Chronic activation of endoplasmic reticulum (ER) stress by mutant Htt (mHtt) results in cellular dysfunction and ultimately cell death. Protein disulfide isomerase (PDI) is a chaperone protein located in the ER. Our previous studies demonstrated that mHtt caused PDI to accumulate at mitochondria-associated ER membranes and triggered cell death, and that modulating PDI activity using small molecules protected cells again mHtt toxicity in cell and brain slice models of HD. In this study, we demonstrated that PDI is upregulated in the HD human brain, in cell and mouse models. Chronic administration of a reversible, brain penetrable small molecule PDI modulator, LOC14 (20 mg/kg/day), significantly improved motor function, attenuated brain atrophy and extended survival in the N171-82Q HD mice. Moreover, LOC14 preserved medium spiny neuronal marker dopamine- and cyclic-AMP-regulated phosphoprotein of molecular weight 32\u00a0000 (DARPP32) levels in the striatum of HD mice. Mechanistic study revealed that LOC14 suppressed mHtt-induced ER stress, indicated by repressing the abnormally upregulated ER stress proteins in HD models. These findings suggest that LOC14 is promising to be further optimized for clinical trials of HD, and modulation of signaling pathways coping with ER stress may constitute an attractive approach to reduce mHtt toxicity and identify new therapeutic targets for treatment of HD.",
+ "publisher": "Acta paediatrica (Oslo, Norway : 1992)",
+ "issn": "1651-2227",
+ "date": "2013-12-27",
+ "abstract": "The purpose of this study was to investigate common polymorphisms in the genes encoding monoamine oxidase A (MAOA) and serotonin transporter (5-HTT) in Norwegian cases of sudden infant death syndrome (SIDS). This was done to further elucidate the role of genetic variation in these genes and SIDS.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29462355"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24286237"
},
{
- "id": "pmid:29378824",
+ "id": "pmid:24047873",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/29378824",
- "title": "Chromosomal instability during neurogenesis in Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/24047873",
+ "title": "Modelling and inference reveal nonlinear length-dependent suppression of somatic instability for small disease associated alleles in myotonic dystrophy type 1 and Huntington disease.",
"type": "article-journal",
- "doi": "10.1242/dev.156844",
+ "doi": "10.1098/rsif.2013.0605",
"authors": [
- ["Albert", "Ruzo"],
- ["Gist F", "Croft"],
- ["Jakob J", "Metzger"],
- ["Szilvia", "Galgoczi"],
- ["Lauren J", "Gerber"],
- ["Cecilia", "Pellegrini"],
- ["Hanbin", "Wang"],
- ["Maria", "Fenner"],
- ["Stephanie", "Tse"],
- ["Adam", "Marks"],
- ["Corbyn", "Nchako"],
- ["Ali H", "Brivanlou"]
+ ["Catherine F", "Higham"],
+ ["Darren G", "Monckton"]
],
- "publisher": "Development (Cambridge, England)",
- "issn": "1477-9129",
- "date": "2018-01-29",
- "abstract": "Huntington's disease (HD) is a fatal neurodegenerative disease caused by expansion of CAG repeats in the Huntingtin gene (",
+ "publisher": "Journal of the Royal Society, Interface",
+ "issn": "1742-5662",
+ "date": "2013-09-18",
+ "abstract": "More than 20 human genetic diseases are associated with inheriting an unstable expanded DNA simple sequence tandem repeat, for example, CTG (cytosine-thymine-guanine) repeats in myotonic dystrophy type 1 (DM1) and CAG (cytosine-adenine-guanine) repeats in Huntington disease (HD). These sequences mutate by changing the number of repeats not just between generations, but also during the lifetime of affected individuals. Levels of somatic instability contribute to disease onset and progression but as changes are tissue-specific, age- and repeat length-dependent, interpretation of the level of somatic instability in an individual is confounded by these considerations. Mathematical models, fitted to CTG repeat length distributions derived from blood DNA, from a large cohort of DM1-affected or at risk individuals, have recently been used to quantify inherited repeat lengths and mutation rates. Taking into account age, the estimated mutation rates are lower than predicted among individuals with small alleles (inherited repeat lengths less than 100 CTGs), suggesting that these rates may be suppressed at the lower end of the disease-causing range. In this study, we propose that a length-specific effect operates within this range and tested this hypothesis using a model comparison approach. To calibrate the extended model, we used data derived from blood DNA from DM1 individuals and, for the first time, buccal DNA from HD individuals. In a novel application of this extended model, we identified individuals whose effective repeat length, with regards to somatic instability, is less than their actual repeat length. A plausible explanation for this distinction is that the expanded repeat tract is compromised by interruptions or other unusual features. We quantified effective length for a large cohort of DM1 individuals and showed that effective length better predicts age of onset than inherited repeat length, thus improving the genotype-phenotype correlation. Under the extended model, we removed some of the bias in mutation rates making them less length-dependent. Consequently, rates adjusted in this way will be better suited as quantitative traits to investigate cis- or trans-acting modifiers of somatic mosaicism, disease onset and progression.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29378824"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24047873"
},
{
- "id": "pmid:29367444",
+ "id": "pmid:24041806",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/29367444",
- "title": "Neurofilament light protein in blood predicts regional atrophy in Huntington disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/24041806",
+ "title": "Oxidative stress causes DNA triplet expansion in Huntington's disease mouse embryonic stem cells.",
"type": "article-journal",
- "doi": "10.1212/wnl.0000000000005005",
+ "doi": "10.1016/j.scr.2013.08.010",
"authors": [
- ["Eileanoir B", "Johnson"],
- ["Lauren M", "Byrne"],
- ["Sarah", "Gregory"],
- ["Filipe B", "Rodrigues"],
- ["Kaj", "Blennow"],
- ["Alexandra", "Durr"],
- ["Blair R", "Leavitt"],
- ["Raymund A", "Roos"],
- ["Henrik", "Zetterberg"],
- ["Sarah J", "Tabrizi"],
- ["Rachael I", "Scahill"],
- ["Edward J", "Wild"]
+ ["Ida", "Jonson"],
+ ["Rune", "Ougland"],
+ ["Arne", "Klungland"],
+ ["Elisabeth", "Larsen"]
],
- "publisher": "Neurology",
- "issn": "1526-632X",
- "date": "2018-01-24",
- "abstract": "Neurofilament light (NfL) protein in blood plasma has been proposed as a prognostic biomarker of neurodegeneration in a number of conditions, including Huntington disease (HD). This study investigates the regional distribution of NfL-associated neural pathology in HD gene expansion carriers.",
+ "publisher": "Stem cell research",
+ "issn": "1876-7753",
+ "date": "2013-08-27",
+ "abstract": "Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded trinucleotide CAG repeat in the Huntingtin (Htt) gene. The molecular basis for the development and progression of HD is currently poorly understood. However, different DNA repair pathways have been implicated in both somatic expansion and disease progression. Embryonic stem cells provide a remarkable in vitro system to study HD and could have implications for understanding disease development and for therapeutic treatment. Here, we derive pluripotent stem cells from the mouse R6/1 HD model and demonstrate that repeated exposure to genotoxic agents inducing oxidative DNA damage gave a significant and dose dependent increase in somatic triplet expansion. Further investigation into specific steps of DNA repair revealed impaired double stranded break repair in exposed R6/1 cells, accompanied by the induction of apoptosis. We also found that differentiation status, and consequently DNA repair efficiency influenced somatic expansion. Our data underscore the importance of DNA damage and repair for the stability of the HD triplet in pluripotent stem cells.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29367444"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24041806"
},
{
- "id": "pmid:29253686",
+ "id": "pmid:24027120",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/29253686",
- "title": "Suicidal ideation and suicidal behavior according to the C-SSRS in a European cohort of Huntington's disease gene expansion carriers.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/24027120",
+ "title": "Nonparametric modeling and analysis of association between Huntington's disease onset and CAG repeats.",
"type": "article-journal",
- "doi": "10.1016/j.jad.2017.11.074",
+ "doi": "10.1002/sim.5971",
"authors": [
- ["Erik", "van Duijn"],
- ["Eslie M", "Vrijmoeth"],
- ["Erik J", "Giltay"],
- ["G", "Bernhard Landwehrmeyer"]
+ ["Yanyuan", "Ma"],
+ ["Yuanjia", "Wang"]
],
- "publisher": "Journal of affective disorders",
- "issn": "1573-2517",
- "date": "2017-11-15",
- "abstract": "Huntington's disease (HD) gene expansion carriers are at an increased risk of suicide, but so far, no studies have investigated the full spectrum of suicidality, including suicidal ideation, suicidal behavior and self-injurious behavior.",
+ "publisher": "Statistics in medicine",
+ "issn": "1097-0258",
+ "date": "2013-09-12",
+ "abstract": "Huntington's disease (HD) is a neurodegenerative disorder with a dominant genetic mode of inheritance caused by an expansion of CAG repeats on chromosome 4. Typically, a longer sequence of CAG repeat length is associated with increased risk of experiencing earlier onset of HD. Previous studies of the association between HD onset age and CAG length have favored a logistic model, where the CAG repeat length enters the mean and variance components of the logistic model in a complex exponential-linear form. To relax the parametric assumption of the exponential-linear association to the true HD onset distribution, we propose to leave both mean and variance functions of the CAG repeat length unspecified and perform semiparametric estimation in this context through a local kernel and backfitting procedure. Motivated by including family history of HD information available in the family members of participants in the Cooperative Huntington's Observational Research Trial (COHORT), we develop the methodology in the context of mixture data, where some subjects have a positive probability of being risk free. We also allow censoring on the age at onset of disease and accommodate covariates other than the CAG length. We study the theoretical properties of the proposed estimator and derive its asymptotic distribution. Finally, we apply the proposed methods to the COHORT data to estimate the HD onset distribution using a group of study participants and the disease family history information available on their family members.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29253686"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24027120"
},
{
- "id": "pmid:29229845",
+ "id": "pmid:24000094",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/29229845",
- "title": "Brain urea increase is an early Huntington's disease pathogenic event observed in a prodromal transgenic sheep model and HD cases.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/24000094",
+ "title": "Relationship of Mediterranean diet and caloric intake to phenoconversion in Huntington disease.",
"type": "article-journal",
- "doi": "10.1073/pnas.1711243115",
+ "doi": "10.1001/jamaneurol.2013.3487",
"authors": [
- ["Renee R", "Handley"],
- ["Suzanne J", "Reid"],
- ["Rudiger", "Brauning"],
- ["Paul", "Maclean"],
- ["Emily R", "Mears"],
- ["Imche", "Fourie"],
- ["Stefano", "Patassini"],
- ["Garth J S", "Cooper"],
- ["Skye R", "Rudiger"],
- ["Clive J", "McLaughlan"],
- ["Paul J", "Verma"],
- ["James F", "Gusella"],
- ["Marcy E", "MacDonald"],
- ["Henry J", "Waldvogel"],
- ["C Simon", "Bawden"],
- ["Richard L M", "Faull"],
- ["Russell G", "Snell"]
+ ["Karen", "Marder"],
+ ["Yian", "Gu"],
+ ["Shirley", "Eberly"],
+ ["Caroline M", "Tanner"],
+ ["Nikolaos", "Scarmeas"],
+ ["David", "Oakes"],
+ ["Ira", "Shoulson"]
],
- "publisher": "Proceedings of the National Academy of Sciences of the United States of America",
- "issn": "1091-6490",
- "date": "2017-12-11",
- "abstract": "The neurodegenerative disorder Huntington's disease (HD) is typically characterized by extensive loss of striatal neurons and the midlife onset of debilitating and progressive chorea, dementia, and psychological disturbance. HD is caused by a CAG repeat expansion in the",
+ "publisher": "JAMA neurology",
+ "issn": "2168-6157",
+ "date": "2013-11-01",
+ "abstract": "Adherence to Mediterranean-type diet (MeDi) may delay onset of Alzheimer and Parkinson diseases. Whether adherence to MeDi affects time to phenoconversion in Huntington disease (HD), a highly penetrant, single-gene disorder, is unknown.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29229845"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24000094"
},
{
- "id": "pmid:29043641",
+ "id": "pmid:23974869",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/29043641",
- "title": "Measuring Dynamic Behavior of Trinucleotide Repeat Tracts In Vivo in Saccharomyces cerevisiae.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23974869",
+ "title": "Glutathione peroxidase activity is neuroprotective in models of Huntington's disease.",
"type": "article-journal",
- "doi": "10.1007/978-1-4939-7306-4_30",
+ "doi": "10.1038/ng.2732",
"authors": [
- ["Gregory M", "Williams"],
- ["Jennifer A", "Surtees"]
+ ["Robert P", "Mason"],
+ ["Massimiliano", "Casu"],
+ ["Nicola", "Butler"],
+ ["Carlo", "Breda"],
+ ["Susanna", "Campesan"],
+ ["Jannine", "Clapp"],
+ ["Edward W", "Green"],
+ ["Devyani", "Dhulkhed"],
+ ["Charalambos P", "Kyriacou"],
+ ["Flaviano", "Giorgini"]
],
- "publisher": "Methods in molecular biology (Clifton, N.J.)",
- "issn": "1940-6029",
- "date": "2018-01-01",
- "abstract": "Trinucleotide repeat (TNR) tracts are inherently unstable during DNA replication, leading to repeat expansions and/or contractions. Expanded tracts are the cause of over 40 neurodegenerative and neuromuscular diseases. In this chapter, we focus on the (CNG)",
+ "publisher": "Nature genetics",
+ "issn": "1546-1718",
+ "date": "2013-08-25",
+ "abstract": "Huntington's disease is a fatal neurodegenerative disorder caused by a CAG repeat expansion encoding a polyglutamine tract in the huntingtin (Htt) protein. Here we report a genome-wide overexpression suppressor screen in which we identified 317 ORFs that ameliorate the toxicity of a mutant Htt fragment in yeast and that have roles in diverse cellular processes, including mitochondrial import and copper metabolism. Two of these suppressors encode glutathione peroxidases (GPxs), which are conserved antioxidant enzymes that catalyze the reduction of hydrogen peroxide and lipid hydroperoxides. Using genetic and pharmacological approaches in yeast, mammalian cells and Drosophila, we found that GPx activity robustly ameliorates Huntington's disease-relevant metrics and is more protective than other antioxidant approaches tested here. Notably, we found that GPx activity, unlike many antioxidant treatments, does not inhibit autophagy, which is an important mechanism for clearing mutant Htt. Because previous clinical trials have indicated that GPx mimetics are well tolerated in humans, this study may have important implications for treating Huntington's disease.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29043641"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23974869"
},
{
- "id": "pmid:28986324",
+ "id": "pmid:23946314",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/28986324",
- "title": "The ubiquitin conjugating enzyme Ube2W regulates solubility of the Huntington's disease protein, huntingtin.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23946314",
+ "title": "De novo Huntington disease caused by 26-44 CAG repeat expansion on a low-risk haplotype.",
"type": "article-journal",
- "doi": "10.1016/j.nbd.2017.10.002",
+ "doi": "10.1212/wnl.0b013e3182a4a4af",
"authors": [
- ["Bo", "Wang"],
- ["Li", "Zeng"],
- ["Sean A", "Merillat"],
- ["Svetlana", "Fischer"],
- ["Joseph", "Ochaba"],
- ["Leslie M", "Thompson"],
- ["Sami J", "Barmada"],
- ["Kenneth M", "Scaglione"],
- ["Henry L", "Paulson"]
+ ["Gunnar", "Houge"],
+ ["Ove", "Bruland"],
+ ["Inga", "Bj\u00f8rnevoll"],
+ ["Michael R", "Hayden"],
+ ["Alicia", "Semaka"]
],
- "publisher": "Neurobiology of disease",
- "issn": "1095-953X",
- "date": "2017-10-03",
- "abstract": "Huntington's disease (HD) is caused by a CAG repeat expansion that encodes a polyglutamine (polyQ) expansion in the HD disease protein, huntingtin (HTT). PolyQ expansion promotes misfolding and aggregation of mutant HTT (mHTT) within neurons. The cellular pathways, including ubiquitin-dependent processes, by which mHTT is regulated remain incompletely understood. Ube2W is the only ubiquitin conjugating enzyme (E2) known to ubiquitinate substrates at their amino (N)-termini, likely favoring substrates with disordered N-termini. By virtue of its N-terminal polyQ domain, HTT has an intrinsically disordered amino terminus. In studies employing immortalized cells, primary neurons and a knock-in (KI) mouse model of HD, we tested the effect of Ube2W deficiency on mHTT levels, aggregation and neurotoxicity. In cultured cells, deficiency of Ube2W activity markedly decreases mHTT aggregate formation and increases the level of soluble monomers, while reducing mHTT-induced cytotoxicity. Consistent with this result, the absence of Ube2W in HdhQ200 KI mice significantly increases levels of soluble monomeric mHTT while reducing insoluble oligomeric species. This study sheds light on the potential function of the non-canonical ubiquitin-conjugating enzyme, Ube2W, in this polyQ neurodegenerative disease.",
+ "publisher": "Neurology",
+ "issn": "1526-632X",
+ "date": "2013-08-14",
+ "abstract": "Huntington disease (HD, OMIM #143100) is a dominantly inherited neurodegenerative disorder due to a CAG repeat expansion in the",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28986324"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23946314"
},
{
- "id": "pmid:28729730",
+ "id": "pmid:23894380",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/28729730",
- "title": "A selective inhibitor of histone deacetylase 3 prevents cognitive deficits and suppresses striatal CAG repeat expansions in Huntington's disease mice.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23894380",
+ "title": "The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients.",
"type": "article-journal",
- "doi": "10.1038/s41598-017-05125-2",
+ "doi": "10.1371/journal.pone.0068951",
"authors": [
- ["Nuria", "Suelves"],
- ["Lucy", "Kirkham-McCarthy"],
- ["Robert S", "Lahue"],
- ["Silvia", "Gin\u00e9s"]
+ ["Silke", "Metzger"],
+ ["Carolin", "Walter"],
+ ["Olaf", "Riess"],
+ ["Raymund A C", "Roos"],
+ ["J\u00f8rgen E", "Nielsen"],
+ ["David", "Craufurd"],
+ ["Huu Phuc", "Nguyen"]
],
- "publisher": "Scientific reports",
- "issn": "2045-2322",
- "date": "2017-07-20",
- "abstract": "Huntington's disease (HD) is a neurodegenerative disorder whose major symptoms include progressive motor and cognitive dysfunction. Cognitive decline is a critical quality of life concern for HD patients and families. The enzyme histone deacetylase 3 (HDAC3) appears to be important in HD pathology by negatively regulating genes involved in cognitive functions. Furthermore, HDAC3 has been implicated in the aberrant transcriptional patterns that help cause disease symptoms in HD mice. HDAC3 also helps fuel CAG repeat expansions in human cells, suggesting that HDAC3 may power striatal expansions in the HTT gene thought to drive disease progression. This multifaceted role suggests that early HDAC3 inhibition offers an attractive mechanism to prevent HD cognitive decline and to suppress striatal expansions. This hypothesis was investigated by treating Hdh",
+ "publisher": "PloS one",
+ "issn": "1932-6203",
+ "date": "2013-07-22",
+ "abstract": "The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the \"REGISTRY\" cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28729730"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23894380"
},
{
- "id": "pmid:28698602",
+ "id": "pmid:23847583",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/28698602",
- "title": "Polyglutamine expansion affects huntingtin conformation in multiple Huntington's disease models.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23847583",
+ "title": "A Tale of Two Maladies? Pathogenesis of Depression with and without the Huntington's Disease Gene Mutation.",
"type": "article-journal",
- "doi": "10.1038/s41598-017-05336-7",
+ "doi": "10.3389/fneur.2013.00081",
"authors": [
- ["Manuel", "Daldin"],
- ["Valentina", "Fodale"],
- ["Cristina", "Cariulo"],
- ["Lucia", "Azzollini"],
- ["Margherita", "Verani"],
- ["Paola", "Martufi"],
- ["Maria Carolina", "Spiezia"],
- ["Sean M", "Deguire"],
- ["Marta", "Cherubini"],
- ["Douglas", "Macdonald"],
- ["Andreas", "Weiss"],
- ["Alberto", "Bresciani"],
- ["Jean-Paul Gerard", "Vonsattel"],
- ["Lara", "Petricca"],
- ["J Lawrence", "Marsh"],
- ["Silvia", "Gines"],
- ["Iolanda", "Santimone"],
- ["Massimo", "Marano"],
- ["Hilal A", "Lashuel"],
- ["Ferdinando", "Squitieri"],
- ["Andrea", "Caricasole"]
+ ["Xin", "Du"],
+ ["Terence Y C", "Pang"],
+ ["Anthony J", "Hannan"]
],
- "publisher": "Scientific reports",
- "issn": "2045-2322",
- "date": "2017-07-11",
- "abstract": "Conformational changes in disease-associated or mutant proteins represent a key pathological aspect of Huntington's disease (HD) and other protein misfolding diseases. Using immunoassays and biophysical approaches, we and others have recently reported that polyglutamine expansion in purified or recombinantly expressed huntingtin (HTT) proteins affects their conformational properties in a manner dependent on both polyglutamine repeat length and temperature but independent of HTT protein fragment length. These findings are consistent with the HD mutation affecting structural aspects of the amino-terminal region of the protein, and support the concept that modulating mutant HTT conformation might provide novel therapeutic and diagnostic opportunities. We now report that the same conformational TR-FRET based immunoassay detects polyglutamine- and temperature-dependent changes on the endogenously expressed HTT protein in peripheral tissues and post-mortem HD brain tissue, as well as in tissues from HD animal models. We also find that these temperature- and polyglutamine-dependent conformational changes are sensitive to bona-fide phosphorylation on S13 and S16 within the N17 domain of HTT. These findings provide key clinical and preclinical relevance to the conformational immunoassay, and provide supportive evidence for its application in the development of therapeutics aimed at correcting the conformation of polyglutamine-expanded proteins as well as the pharmacodynamics readouts to monitor their efficacy in preclinical models and in HD patients.",
+ "publisher": "Frontiers in neurology",
+ "issn": "1664-2295",
+ "date": "2013-07-09",
+ "abstract": "Huntington's disease (HD) is an autosomal dominant disorder caused by a tandem repeat expansion encoding an expanded tract of glutamines in the huntingtin protein. HD is progressive and manifests as psychiatric symptoms (including depression), cognitive deficits (culminating in dementia), and motor abnormalities (including chorea). Having reached the twentieth anniversary of the discovery of the \"genetic stutter\" which causes HD, we still lack sophisticated insight into why so many HD patients exhibit affective disorders such as depression at very early stages, prior to overt appearance of motor deficits. In this review, we will focus on depression as the major psychiatric manifestation of HD, discuss potential mechanisms of pathogenesis identified from animal models, and compare depression in HD patients with that of the wider gene-negative population. The discovery of depressive-like behaviors as well as cellular and molecular correlates of depression in transgenic HD mice has added strong support to the hypothesis that the HD mutation adds significantly to the genetic load for depression. A key question is whether HD-associated depression differs from that in the general population. Whilst preclinical studies, clinical data, and treatment responses suggest striking similarities, there are also some apparent differences. We discuss various molecular and cellular mechanisms which may contribute to depression in HD, and whether they may generalize to other depressive disorders. The autosomal dominant nature of HD and the existence of models with excellent construct validity provide a unique opportunity to understand the pathogenesis of depression and associated gene-environment interactions. Thus, understanding the pathogenesis of depression in HD may not only facilitate tailored therapeutic approaches for HD sufferers, but may also translate to the clinical depression which devastates the lives of so many people.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28698602"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23847583"
},
{
- "id": "pmid:28642124",
+ "id": "pmid:23765727",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/28642124",
- "title": "Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23765727",
+ "title": "Allele-specific expression of the serotonin transporter and its transcription factors following lamotrigine treatment in vitro.",
"type": "article-journal",
- "doi": "10.1016/s1474-4422(17)30161-8",
+ "doi": "10.1002/ajmg.b.32178",
"authors": [
- ["Davina J Hensman", "Moss"],
- ["Antonio F", "Pardi\u00f1as"],
- ["Douglas", "Langbehn"],
- ["Kitty", "Lo"],
- ["Blair R", "Leavitt"],
- ["Raymund", "Roos"],
- ["Alexandra", "Durr"],
- ["Simon", "Mead"],
- ["Peter", "Holmans"],
- ["Lesley", "Jones"],
- ["Sarah J", "Tabrizi"]
+ ["Ursula M", "D'Souza"],
+ ["Georgia", "Powell-Smith"],
+ ["Kate", "Haddley"],
+ ["Timothy R", "Powell"],
+ ["Vivien J", "Bubb"],
+ ["Tom", "Price"],
+ ["Peter", "McGuffin"],
+ ["John P", "Quinn"],
+ ["Anne E", "Farmer"]
],
- "publisher": "The Lancet. Neurology",
- "issn": "1474-4465",
- "date": "2017-06-20",
- "abstract": "Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure.",
+ "publisher": "American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics",
+ "issn": "1552-485X",
+ "date": "2013-06-14",
+ "abstract": "Lamotrigine, a mood stabilizer used clinically in the treatment of bipolar disorder, is thought to exert actions on the serotonin system. However lamotrigine's exact mechanism of action remains unclear. The current study investigated whether lamotrigine might exert its effects through altering the expression of the serotonin transporter (5-HTT) gene and its regulatory transcription factors Y box binding protein 1 (YB-1) and CCCTC-binding factor (CTCF). We further considered whether functional variable number tandem repeat (VNTR) polymorphisms in the promoter region of 5-HTT, (5-HTTLPR) and within intron 2 (Stin2) of the gene, moderated any putative gene expression changes. The study employed an in vitro design carried out in human lymphoblastoid cell lines (LCLs) to investigate the effects of lamotrigine treatment at 0.04, 0.2, and 0.4\u2009mM doses for 24\u2009hr on the mRNA expression of 5-HTT, YB-1, and CTCF. LCLs were selected based on combinations of haplotypes of the two VNTRs in the serotonin transporter gene; creating low-expressing and high-expressing LCL groups. Ubiquitin C (UBC) and topoisomerase I (TOP1) genes were found to be the most stably expressed housekeeping genes in drug-treated LCLs. Subsequently, quantitative PCR revealed that higher doses of lamotrigine significantly lowered 5-HTT expression and increased CTCF expression. Haplotype-specific differences in CTCF expression were found in response to lamotrigine, with strongest expression changes observed in the high-expressing LCLs. These data provide an allele-specific in vitro model for examining the molecular targets of lamotrigine, and support the important role of the serotonin transporter gene in its clinical mechanism of action.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28642124"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23765727"
},
{
- "id": "pmid:28582868",
+ "id": "pmid:23644918",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/28582868",
- "title": "Dynamic Prediction of Motor Diagnosis in\u00a0Huntington's Disease Using a Joint Modeling Approach.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23644918",
+ "title": "Candidate glutamatergic and dopaminergic pathway gene variants do not influence Huntington's disease motor onset.",
"type": "article-journal",
- "doi": "10.3233/jhd-170236",
+ "doi": "10.1007/s10048-013-0364-y",
"authors": [
- ["Kan", "Li"],
- ["Erin", "Furr-Stimming"],
- ["Jane S", "Paulsen"],
- ["Sheng", "Luo"]
+ ["Eliana Marisa", "Ramos"],
+ ["Jeanne C", "Latourelle"],
+ ["Tammy", "Gillis"],
+ ["Jayalakshmi S", "Mysore"],
+ ["Ferdinando", "Squitieri"],
+ ["Alba", "Di Pardo"],
+ ["Stefano", "Di Donato"],
+ ["Cinzia", "Gellera"],
+ ["Michael R", "Hayden"],
+ ["Patrick J", "Morrison"],
+ ["Martha", "Nance"],
+ ["Christopher A", "Ross"],
+ ["Russell L", "Margolis"],
+ ["Estrella", "Gomez-Tortosa"],
+ ["Carmen", "Ayuso"],
+ ["Oksana", "Suchowersky"],
+ ["Ronald J", "Trent"],
+ ["Elizabeth", "McCusker"],
+ ["Andrea", "Novelletto"],
+ ["Marina", "Frontali"],
+ ["Randi", "Jones"],
+ ["Tetsuo", "Ashizawa"],
+ ["Samuel", "Frank"],
+ ["Marie-Helene", "Saint-Hilaire"],
+ ["Steven M", "Hersch"],
+ ["Herminia D", "Rosas"],
+ ["Diane", "Lucente"],
+ ["Madaline B", "Harrison"],
+ ["Andrea", "Zanko"],
+ ["Ruth K", "Abramson"],
+ ["Karen", "Marder"],
+ ["James F", "Gusella"],
+ ["Jong-Min", "Lee"],
+ ["Isabel", "Alonso"],
+ ["Jorge", "Sequeiros"],
+ ["Richard H", "Myers"],
+ ["Marcy E", "Macdonald"]
],
- "publisher": "Journal of Huntington's disease",
- "issn": "1879-6400",
- "date": "2017-01-01",
- "abstract": "Prediction of motor diagnosis in Huntington's disease (HD) can be improved by incorporating other phenotypic and biological clinical measures in addition to cytosine-adenine-guanine (CAG) repeat length and age.",
+ "publisher": "Neurogenetics",
+ "issn": "1364-6753",
+ "date": "2013-05-04",
+ "abstract": "Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and behavioral disturbances. It is caused by the expansion of the HTT CAG repeat, which is the major determinant of age at onset (AO) of motor symptoms. Aberrant function of N-methyl-D-aspartate receptors and/or overexposure to dopamine has been suggested to cause significant neurotoxicity, contributing to HD pathogenesis. We used genetic association analysis in 1,628 HD patients to evaluate candidate polymorphisms in N-methyl-D-aspartate receptor subtype genes (GRIN2A rs4998386 and rs2650427, and GRIN2B rs1806201) and functional polymorphisms in genes in the dopamine pathway (DAT1 3' UTR 40-bp variable number tandem repeat (VNTR), DRD4 exon 3 48-bp VNTR, DRD2 rs1800497, and COMT rs4608) as potential modifiers of the disease process. None of the seven polymorphisms tested was found to be associated with significant modification of motor AO, either in a dominant or additive model, after adjusting for ancestry. The results of this candidate-genetic study therefore do not provide strong evidence to support a modulatory role for these variations within glutamatergic and dopaminergic genes in the AO of HD motor manifestations.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28582868"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23644918"
},
{
- "id": "pmid:28406926",
+ "id": "pmid:23624566",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/28406926",
- "title": "High-resolution respirometry of fine-needle muscle biopsies in pre-manifest Huntington's disease expansion mutation carriers shows normal mitochondrial respiratory function.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23624566",
+ "title": "Characterization of the Huntington intermediate CAG repeat expansion phenotype in PHAROS.",
"type": "article-journal",
- "doi": "10.1371/journal.pone.0175248",
+ "doi": "10.1212/wnl.0b013e318294b304",
"authors": [
- ["Eva", "Buck"],
- ["Martina", "Z\u00fcgel"],
- ["Uwe", "Schumann"],
- ["Tamara", "Merz"],
- ["Anja M", "Gumpp"],
- ["Anke", "Witting"],
- ["J\u00fcrgen M", "Steinacker"],
- ["G Bernhard", "Landwehrmeyer"],
- ["Patrick", "Weydt"],
- ["Enrico", "Calzia"],
- ["Katrin S", "Lindenberg"]
+ ["Annie", "Killoran"],
+ ["Kevin M", "Biglan"],
+ ["Joseph", "Jankovic"],
+ ["Shirley", "Eberly"],
+ ["Elise", "Kayson"],
+ ["David", "Oakes"],
+ ["Anne B", "Young"],
+ ["Ira", "Shoulson"]
],
- "publisher": "PloS one",
- "issn": "1932-6203",
- "date": "2017-04-13",
- "abstract": "Alterations in mitochondrial respiration are an important hallmark of Huntington's disease (HD), one of the most common monogenetic causes of neurodegeneration. The ubiquitous expression of the disease causing mutant huntingtin gene raises the prospect that mitochondrial respiratory deficits can be detected in skeletal muscle. While this tissue is readily accessible in humans, transgenic animal models offer the opportunity to cross-validate findings and allow for comparisons across organs, including the brain. The integrated respiratory chain function of the human vastus lateralis muscle was measured by high-resolution respirometry (HRR) in freshly taken fine-needle biopsies from seven pre-manifest HD expansion mutation carriers and nine controls. The respiratory parameters were unaffected. For comparison skeletal muscle isolated from HD knock-in mice (HdhQ111) as well as a broader spectrum of tissues including cortex, liver and heart muscle were examined by HRR. Significant changes of mitochondrial respiration in the HdhQ knock-in mouse model were restricted to the liver and the cortex. Mitochondrial mass as quantified by mitochondrial DNA copy number and citrate synthase activity was stable in murine HD-model tissue compared to control. mRNA levels of key enzymes were determined to characterize mitochondrial metabolic pathways in HdhQ mice. We demonstrated the feasibility to perform high-resolution respirometry measurements from small human HD muscle biopsies. Furthermore, we conclude that alterations in respiratory parameters of pre-manifest human muscle biopsies are rather limited and mirrored by a similar absence of marked alterations in HdhQ skeletal muscle. In contrast, the HdhQ111 murine cortex and liver did show respiratory alterations highlighting the tissue specific nature of mutant huntingtin effects on respiration.",
+ "publisher": "Neurology",
+ "issn": "1526-632X",
+ "date": "2013-04-26",
+ "abstract": "We aimed to describe the clinical phenotype conferred by the intermediate-length huntingtin allele CAG repeat expansion in a population-based study.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28406926"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23624566"
},
{
- "id": "pmid:28359739",
+ "id": "pmid:23595883",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/28359739",
- "title": "2,4 DNP improves motor function, preserves medium spiny neuronal identity, and reduces oxidative stress in a mouse model of Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23595883",
+ "title": "Dominant effects of the Huntington's disease HTT CAG repeat length are captured in gene-expression data sets by a continuous analysis mathematical modeling strategy.",
"type": "article-journal",
- "doi": "10.1016/j.expneurol.2017.03.020",
+ "doi": "10.1093/hmg/ddt176",
"authors": [
- ["Bin", "Wu"],
- ["Mali", "Jiang"],
- ["Qi", "Peng"],
- ["Gang", "Li"],
- ["Zhipeng", "Hou"],
- ["Ginger L", "Milne"],
- ["Susumu", "Mori"],
- ["Robert", "Alonso"],
- ["John G", "Geisler"],
- ["Wenzhen", "Duan"]
+ ["Jong-Min", "Lee"],
+ ["Ekaterina I", "Galkina"],
+ ["Rachel M", "Levantovsky"],
+ ["Elisa", "Fossale"],
+ ["Mary", "Anne Anderson"],
+ ["Tammy", "Gillis"],
+ ["Jayalakshmi", "Srinidhi Mysore"],
+ ["Kathryn R", "Coser"],
+ ["Toshi", "Shioda"],
+ ["Bin", "Zhang"],
+ ["Matthew D", "Furia"],
+ ["Jonathan", "Derry"],
+ ["Isaac S", "Kohane"],
+ ["Ihn Sik", "Seong"],
+ ["Vanessa C", "Wheeler"],
+ ["James F", "Gusella"],
+ ["Marcy E", "MacDonald"]
],
- "publisher": "Experimental neurology",
- "issn": "1090-2430",
- "date": "2017-03-28",
- "abstract": "Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in the first exon of the gene huntingtin. There is no treatment to prevent or delay the disease course of HD currently. Oxidative stress and mitochondrial dysfunction have emerged as key determinants of the disease progression in HD. Therefore, counteracting mutant huntingtin (mHtt)-induced oxidative stress and mitochondrial dysfunction appears as a new approach to treat this devastating disease. Interestingly, mild mitochondrial uncoupling improves neuronal resistance to stress and facilitates neuronal survival. Mild mitochondrial uncoupling can be induced by the proper dose of 2,4-dinitrophenol (DNP), a proton ionophore that was previously used for weight loss. In this study, we evaluated the effects of chronic administration of DNP at three doses (0.5, 1, 5mg/kg/day) on mHtt-induced behavioral deficits and cellular abnormalities in the N171-82Q HD mouse model. DNP at a low dose (1mg/kg/day) significantly improved motor function and preserved medium spiny neuronal marker DARPP32 and postsynaptic protein PSD95 in the striatum of HD mice. Further mechanistic study suggests that DNP at this dose reduced oxidative stress in HD mice, which was indicated by reduced levels of F2-isoprostanes in the brain of HD mice treated with DNP. Our data indicated that DNP provided behavioral benefit and neuroprotective effect at a weight neutral dose in HD mice, suggesting that the potential value of repositioning DNP to HD treatment is warranted in well-controlled clinical trials in HD.",
+ "publisher": "Human molecular genetics",
+ "issn": "1460-2083",
+ "date": "2013-04-16",
+ "abstract": "In Huntington's disease (HD), the size of the expanded HTT CAG repeat mutation is the primary driver of the processes that determine age at onset of motor symptoms. However, correlation of cellular biochemical parameters also extends across the normal repeat range, supporting the view that the CAG repeat represents a functional polymorphism with dominant effects determined by the longer allele. A central challenge to defining the functional consequences of this single polymorphism is the difficulty of distinguishing its subtle effects from the multitude of other sources of biological variation. We demonstrate that an analytical approach based upon continuous correlation with CAG size was able to capture the modest (\u223c21%) contribution of the repeat to the variation in genome-wide gene expression in 107 lymphoblastoid cell lines, with alleles ranging from 15 to 92 CAGs. Furthermore, a mathematical model from an iterative strategy yielded predicted CAG repeat lengths that were significantly positively correlated with true CAG allele size and negatively correlated with age at onset of motor symptoms. Genes negatively correlated with repeat size were also enriched in a set of genes whose expression were CAG-correlated in human HD cerebellum. These findings both reveal the relatively small, but detectable impact of variation in the CAG allele in global data in these peripheral cells and provide a strategy for building multi-dimensional data-driven models of the biological network that drives the HD disease process by continuous analysis across allelic panels of neuronal cells vulnerable to the dominant effects of the HTT CAG repeat.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28359739"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23595883"
},
{
- "id": "pmid:28205498",
+ "id": "pmid:23576953",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/28205498",
- "title": "Cognitive Control, Learning, and Clinical Motor Ratings Are Most Highly Associated with Basal Ganglia Brain Volumes in the Premanifest Huntington's Disease Phenotype.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23576953",
+ "title": "Characterization of forebrain neurons derived from late-onset Huntington's disease human embryonic stem cell lines.",
"type": "article-journal",
- "doi": "10.1017/s1355617716001132",
+ "doi": "10.3389/fncel.2013.00037",
"authors": [
- ["Maria B", "Misiura"],
- ["Spencer", "Lourens"],
- ["Vince D", "Calhoun"],
- ["Jeffrey", "Long"],
- ["Jeremy", "Bockholt"],
- ["Hans", "Johnson"],
- ["Ying", "Zhang"],
- ["Jane S", "Paulsen"],
- ["Jessica A", "Turner"],
- ["Jingyu", "Liu"],
- ["Betul", "Kara"],
- ["Elizabeth", "Fall"]
+ ["Jonathan C", "Niclis"],
+ ["Anita", "Pinar"],
+ ["John M", "Haynes"],
+ ["Walaa", "Alsanie"],
+ ["Robert", "Jenny"],
+ ["Mirella", "Dottori"],
+ ["David S", "Cram"]
],
- "publisher": "Journal of the International Neuropsychological Society : JINS",
- "issn": "1469-7661",
- "date": "2017-02-01",
- "abstract": "Huntington's disease (HD) is a debilitating genetic disorder characterized by motor, cognitive and psychiatric abnormalities associated with neuropathological decline. HD pathology is the result of an extended chain of CAG (cytosine, adenine, guanine) trinucleotide repetitions in the HTT gene. Clinical diagnosis of HD requires the presence of an otherwise unexplained extrapyramidal movement disorder in a participant at risk for HD. Over the past 15 years, evidence has shown that cognitive, psychiatric, and subtle motor dysfunction is evident decades before traditional motor diagnosis. This study examines the relationships among subcortical brain volumes and measures of emerging disease phenotype in prodromal HD, before clinical diagnosis.",
+ "publisher": "Frontiers in cellular neuroscience",
+ "issn": "1662-5102",
+ "date": "2013-04-05",
+ "abstract": "Huntington's disease (HD) is an incurable neurodegenerative disorder caused by a CAG repeat expansion in exon 1 of the Huntingtin (HTT) gene. Recently, induced pluripotent stem cell (iPSC) lines carrying atypical and aggressive (CAG60+) HD variants have been generated and exhibit disparate molecular pathologies. Here we investigate two human embryonic stem cell (hESC) lines carrying CAG37 and CAG51 typical late-onset repeat expansions in comparison to wildtype control lines during undifferentiated states and throughout forebrain neuronal differentiation. Pluripotent HD lines demonstrate growth, viability, pluripotent gene expression, mitochondrial activity and forebrain specification that is indistinguishable from control lines. Expression profiles of crucial genes known to be dysregulated in HD remain unperturbed in the presence of mutant protein and throughout differentiation; however, elevated glutamate-evoked responses were observed in HD CAG51 neurons. These findings suggest typical late-onset HD mutations do not alter pluripotent parameters or the capacity to generate forebrain neurons, but that such progeny may recapitulate hallmarks observed in established HD model systems. Such HD models will help further our understanding of the cascade of pathological events leading to disease onset and progression, while simultaneously facilitating the identification of candidate HD therapeutics.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28205498"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23576953"
},
{
- "id": "pmid:28202696",
+ "id": "pmid:23480802",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/28202696",
- "title": "Low cancer prevalence in polyglutamine expansion diseases.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23480802",
+ "title": "Biomarkers for Huntington's disease: an update.",
"type": "article-journal",
- "doi": "10.1212/wnl.0000000000003725",
+ "doi": "10.1517/17530059.2012.701205",
"authors": [
- ["Giulia", "Coarelli"],
- ["Alhassane", "Diallo"],
- ["Morgane Sonia", "Thion"],
- ["Daisy", "Rinaldi"],
- ["Fabienne", "Calvas"],
- ["Ouahid Lagha", "Boukbiza"],
- ["Alina", "Tataru"],
- ["Perrine", "Charles"],
- ["Christine", "Tranchant"],
- ["Cecilia", "Marelli"],
- ["Claire", "Ewenczyk"],
- ["Maya", "Tchikviladz\u00e9"],
- ["Marie-Lorraine", "Monin"],
- ["Bertrand", "Carlander"],
- ["Mathieu", "Anheim"],
- ["Alexis", "Brice"],
- ["Fanny", "Mochel"],
- ["Sophie", "Tezenas du Montcel"],
- ["Sandrine", "Humbert"],
- ["Alexandra", "Durr"]
+ ["Rachael I", "Scahill"],
+ ["Ed J", "Wild"],
+ ["Sarah J", "Tabrizi"]
],
- "publisher": "Neurology",
- "issn": "1526-632X",
- "date": "2017-02-15",
- "abstract": "Polyglutamine (PolyQ) diseases are dominantly transmitted neurologic disorders, caused by coding and expanded CAG trinucleotide repeats. Cancer was reported retrospectively to be rare in patients with PolyQ diseases and we aimed to investigate its prevalence in France.",
+ "publisher": "Expert opinion on medical diagnostics",
+ "issn": "1753-0067",
+ "date": "2012-06-24",
+ "abstract": "Huntington's disease (HD) is a devastating autosomal-dominant neurodegenerative condition caused by a CAG repeat expansion in the gene encoding huntingtin which is characterised by progressive motor impairment, cognitive decline and neuropsychiatric disturbances. There are currently no disease-modifying treatments available to patients, but a number of therapeutic strategies are currently being investigated, chief among them are nucleotide-based 'gene silencing' approaches, modulation of huntingtin post-translation modification and enhancing clearance of the mutant protein. In 2008, the authors' review highlighted the need to develop and validate biomarkers and provided a systematic head-to-head comparison of such measures. They searched the PubMed database for publications, which covered each of the subheadings mentioned below. They identified from these list studies which had relevance to biomarker development, as defined in their previous review. Building on a tradition of collaborative research in HD, great advances have been made in the field since that time and a range of outcome measures are now being recommended in order to assess efficacy in future therapeutic trials.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28202696"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23480802"
},
{
- "id": "pmid:28153533",
+ "id": "pmid:23443539",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/28153533",
- "title": "Dysregulation of gene expression in the striatum of BACHD rats expressing full-length mutant huntingtin and associated abnormalities on molecular and protein levels.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23443539",
+ "title": "Translation of HTT mRNA with expanded CAG repeats is regulated by the MID1-PP2A protein complex.",
"type": "article-journal",
- "doi": "10.1016/j.neuropharm.2017.01.029",
+ "doi": "10.1038/ncomms2514",
"authors": [
- ["Libo", "Yu-Taeger"],
- ["Michael", "Bonin"],
- ["Janice", "Stricker-Shaver"],
- ["Olaf", "Riess"],
- ["Hoa Huu Phuc", "Nguyen"]
+ ["Sybille", "Krauss"],
+ ["Nadine", "Griesche"],
+ ["Ewa", "Jastrzebska"],
+ ["Changwei", "Chen"],
+ ["D\u00e9siree", "Rutschow"],
+ ["Clemens", "Achm\u00fcller"],
+ ["Stephanie", "Dorn"],
+ ["Sylvia M", "Boesch"],
+ ["Maciej", "Lalowski"],
+ ["Erich", "Wanker"],
+ ["Rainer", "Schneider"],
+ ["Susann", "Schweiger"]
],
- "publisher": "Neuropharmacology",
- "issn": "1873-7064",
- "date": "2017-01-30",
- "abstract": "Huntington disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the gene coding for the huntingtin protein (HTT). Mutant HTT (mHTT) has been proposed to cause neuronal dysfunction and neuronal loss through multiple mechanisms. Transcriptional changes may be a core pathogenic feature of HD. Utilizing the Affymetrix platform we performed a genome-wide RNA expression analysis in two BACHD transgenic rat lines (TG5 and TG9) at 12 months of age, both of which carry full-length human mHTT but with different expression levels. By defining the threshold of significance at p\u00a0<\u00a00.01, we found 1608 genes and 871 genes differentially expressed in both TG5 and TG9 rats when compared to the wild type littermates, respectively. We only chose the highly up-/down-regulated genes for further analysis by setting an additional threshold of 1.5 fold change. Comparing gene expression profiles of human HD brains and BACHD rats revealed a high concordance in both functional and IPA (Ingenuity Pathway Analysis) canonical pathways relevant to HD. In addition, we investigated the causes leading to gene expression changes at molecular and protein levels in BACHD rats including the involvement of polyQ-containing transcription factors TATA box-binding protein (TBP), Sp1 and CBP as well as the chromatin structure. We demonstrate that the BACHD rat model recapitulates the gene expression changes of the human disease supporting its role as a preclinical research animal model. We also show for the first time that TFIID complex formation is reduced, while soluble TBP is increased in an HD model. This finding suggests that mHTT is a competitor instead of a recruiter of polyQ-containing transcription factors in the transcription process in HD.",
+ "publisher": "Nature communications",
+ "issn": "2041-1723",
+ "date": "2013-01-01",
+ "abstract": "Expansion of CAG repeats is a common feature of various neurodegenerative disorders, including Huntington's disease. Here we show that expanded CAG repeats bind to a translation regulatory protein complex containing MID1, protein phosphatase 2A and 40S ribosomal S6 kinase. Binding of the MID1-protein phosphatase 2A protein complex increases with CAG repeat size and stimulates translation of the CAG repeat expansion containing messenger RNA in a MID1-, protein phosphatase 2A- and mammalian target of rapamycin-dependent manner. Our data indicate that pathological CAG repeat expansions upregulate protein translation leading to an overproduction of aberrant protein and suggest that the MID1-complex may serve as a therapeutic target for the treatment of CAG repeat expansion disorders.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28153533"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23443539"
},
{
- "id": "pmid:28000697",
+ "id": "pmid:23440000",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/28000697",
- "title": "The targetable A1 Huntington disease haplotype has distinct Amerindian and European origins in Latin America.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23440000",
+ "title": "Intermediate CAG Repeats in Huntington's Disease: Analysis of COHORT.",
"type": "article-journal",
- "doi": "10.1038/ejhg.2016.169",
+ "doi": "10.7916/d8ff3r2p",
"authors": [
- ["Chris", "Kay"],
- ["Indira", "Tirado-Hurtado"],
- ["Mario", "Cornejo-Olivas"],
- ["Jennifer A", "Collins"],
- ["Galen", "Wright"],
- ["Miguel", "Inca-Martinez"],
- ["Diego", "Veliz-Otani"],
- ["Maria E", "Ketelaar"],
- ["Ramy A", "Slama"],
- ["Colin J", "Ross"],
- ["Pilar", "Mazzetti"],
- ["Michael R", "Hayden"]
- ],
- "publisher": "European journal of human genetics : EJHG",
- "issn": "1476-5438",
- "date": "2016-12-21",
- "abstract": "Huntington disease (HD) is a dominant neurodegenerative disorder caused by a CAG repeat expansion in the Huntingtin (HTT) gene. HD occurs worldwide, but the causative mutation is found on different HTT haplotypes in distinct ethnic groups. In Latin America, HD is thought to have European origins, but indigenous Amerindian ancestry has not been investigated. Here, we report dense HTT haplotypes in 62 mestizo Peruvian HD families, 17 HD families from across Latin America, and 42 controls of defined Peruvian Amerindian ethnicity to determine the origin of HD in populations of admixed Amerindian and European descent. HD in Peru occurs most frequently on the A1 HTT haplotype (73%), as in Europe, but on an unexpected indigenous variant also found in Amerindian controls. This Amerindian A1 HTT haplotype predominates over the European A1 variant among geographically disparate Latin American controls and in HD families from across Latin America, supporting an indigenous origin of the HD mutation in mestizo American populations. We also show that a proportion of HD mutations in Peru occur on a C1 HTT haplotype of putative Amerindian origin (14%). The majority of HD mutations in Latin America may therefore occur on haplotypes of Amerindian ancestry rather than on haplotypes resulting from European admixture. Despite the distinct ethnic ancestry of Amerindian and European A1 HTT, alleles on the parent A1 HTT haplotype allow for development of identical antisense molecules to selectively silence the HD mutation in the greatest proportion of patients in both Latin American and European populations.",
+ ["Ainhi D", "Ha"],
+ ["Christopher A", "Beck"],
+ ["Joseph", "Jankovic"]
+ ],
+ "publisher": "Tremor and other hyperkinetic movements (New York, N.Y.)",
+ "issn": "2160-8288",
+ "date": "2012-02-02",
+ "abstract": "There is emerging evidence that clinical and neuro-pathological manifestations of Huntington's disease (HD) may occur in individuals with intermediate length cytosine-adenine-guanine (CAG) repeats (27-35 CAG repeats) in the Huntingtin (HTT) gene. We aim to further define the clinical characteristics of individuals who possess CAG repeat lengths in this range.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28000697"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23440000"
},
{
- "id": "pmid:27983559",
+ "id": "pmid:23398026",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/27983559",
- "title": "Phenotype Characterization of HD Intermediate Alleles in PREDICT-HD.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23398026",
+ "title": "Clinical features of Chinese patients with Huntington's disease carrying CAG repeats beyond 60 within HTT gene.",
"type": "article-journal",
- "doi": "10.3233/jhd-160185",
+ "doi": "10.1111/cge.12120",
"authors": [
- ["Nancy R", "Downing"],
- ["Spencer", "Lourens"],
- ["Isabella", "De Soriano"],
- ["Jeffrey D", "Long"],
- ["Jane S", "Paulsen"]
+ ["Z-J", "Liu"],
+ ["Y-M", "Sun"],
+ ["W", "Ni"],
+ ["Y", "Dong"],
+ ["S-S", "Shi"],
+ ["Z-Y", "Wu"]
],
- "publisher": "Journal of Huntington's disease",
- "issn": "1879-6400",
- "date": "2016-12-15",
- "abstract": "Huntington disease (HD) is a neurodegenerative disease caused by a CAG repeat expansion on chromosome 4. Pathology is associated with CAG repeat length. Prior studies examining people in the intermediate allele (IA) range found subtle differences in motor, cognitive, and behavioral domains compared to controls.",
+ "publisher": "Clinical genetics",
+ "issn": "1399-0004",
+ "date": "2013-03-11",
+ "abstract": "Patients with Huntington's disease (HD) carrying CAG repeats beyond 60 are less frequently seen and clinical features of them have been rarely reported. We identified four unrelated patients carrying CAG repeats beyond 60 (84.0 \u00b1 13.76, ranging from 74 to 104) from 119 Chinese HD patients via direct sequencing. These four were all early onset with a mean age at presenting symptom of 9.8 \u00b1 1.71 years. Paternal transmission was found in three of them and the fourth was apparently sporadic. In addition, they had atypical onset symptoms including epilepsy, intellectual decline, tics and walking instability, which might lead the clinicians to make the wrong diagnosis in the early stage of disease. Our work explores clinical features of Chinese HD patients with an expanded CAG repeat over 60 and may help the clinicians make a correct diagnosis in the early stage of disease.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27983559"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23398026"
},
{
- "id": "pmid:27870408",
+ "id": "pmid:23372043",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/27870408",
- "title": "Sex-specific effects of the Huntington gene on normal neurodevelopment.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23372043",
+ "title": "A critical role of astrocyte-mediated nuclear factor-\u03baB-dependent inflammation in Huntington's disease.",
"type": "article-journal",
- "doi": "10.1002/jnr.23980",
+ "doi": "10.1093/hmg/ddt036",
"authors": [
- ["Jessica K", "Lee"],
- ["Yue", "Ding"],
- ["Amy L", "Conrad"],
- ["Elena", "Cattaneo"],
- ["Eric", "Epping"],
- ["Kathy", "Mathews"],
- ["Pedro", "Gonzalez-Alegre"],
- ["Larry", "Cahill"],
- ["Vincent", "Magnotta"],
- ["Bradley L", "Schlaggar"],
- ["Joel S", "Perlmutter"],
- ["Regina E Y", "Kim"],
- ["Jeffrey D", "Dawson"],
- ["Peg", "Nopoulos"]
+ ["Han-Yun", "Hsiao"],
+ ["Yu-Chen", "Chen"],
+ ["Hui-Mei", "Chen"],
+ ["Pang-Hsien", "Tu"],
+ ["Yijuang", "Chern"]
],
- "publisher": "Journal of neuroscience research",
- "issn": "1097-4547",
- "date": "2017-01-02",
- "abstract": "Huntington disease is a neurodegenerative disorder caused by a gene (HTT) with a unique feature of trinucleotide repeats ranging from 10 to 35 in healthy people; when expanded beyond 39 repeats, Huntington disease develops. Animal models demonstrate that HTT is vital to brain development; however, this has not been studied in humans. Moreover, evidence suggests that triplet repeat genes may have been vital in evolution of the human brain. Here we evaluate brain structure using magnetic resonance imaging and brain function using cognitive tests in a sample of school-aged children ages 6 to 18 years old. DNA samples were processed to quantify the number of CAG repeats within HTT. We find that the number of repeats in HTT, below disease threshold, confers advantageous changes in brain structure and general intelligence (IQ): the higher the number of repeats, the greater the change in brain structure, and the higher the IQ. The pattern of structural brain changes associated with HTT is strikingly different between males and females. HTT may confer an advantage or a disadvantage depending on the repeat length, playing a key role in either the evolution of a superior human brain or development of a uniquely human brain disease. \u00a9 2016 Wiley Periodicals, Inc.",
+ "publisher": "Human molecular genetics",
+ "issn": "1460-2083",
+ "date": "2013-01-30",
+ "abstract": "Huntington's disease (HD) is an autosomal disease caused by a CAG repeat expansion in the huntingtin (HTT) gene. The resultant mutant HTT protein (mHTT) forms aggregates in various types of cells, including neurons and glial cells and preferentially affects brain function. We found that two HD mouse models (Hdh(150Q) and R6/2) were more susceptible than wild-type (WT) mice to lipopolysaccharide-evoked systemic inflammation and produced more proinflammatory cytokines in the brain. Such an enhanced inflammatory response in the brain was not observed in N171- 82Q mice that express mHTT only in neurons, but not in glial cells. Thus, HD glia might play an important role in chronic inflammation that accelerates disease progression in HD mice. Intriguingly, enhanced activation of nuclear factor (NF)-\u03baB-p65 (p65), a transcriptional mediator of inflammatory responses, was observed in astrocytes of patients and mice with HD. Results obtained using primary R6/2 astrocytes suggest that these cells exhibited higher I\u03baB kinase (IKK) activity that caused prolongation of NF-\u03baB activation, thus upregulating proinflammatory factors during inflammation. R6/2 astrocytes also produced a more-damaging effect on primary R6/2 neurons than did WT astrocytes during inflammation. Blockage of IKK reduced the neuronal toxicity caused by R6/2 astrocytes and ameliorated several HD symptoms of R6/2 mice (e.g. decreased neuronal density, impaired motor coordination and poor cognitive function). Collectively, our results indicate that enhancement of the p65-mediated inflammatory response in astrocytes contributes to HD pathogenesis. Therapeutic interventions aimed at preventing neuronal inflammation may be an important strategy for treating HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27870408"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23372043"
},
{
- "id": "pmid:27681197",
+ "id": "pmid:23346156",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/27681197",
- "title": "Mycobacterium tuberculosis multi-drug-resistant strain M induces IL-17",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23346156",
+ "title": "Decreased Metabolism in the Cerebral Cortex in Early-Stage Huntington's Disease: A Possible Biomarker of Disease Progression?",
"type": "article-journal",
- "doi": "10.1111/cei.12873",
+ "doi": "10.3988/jcn.2013.9.1.21",
"authors": [
- ["J I", "Basile"],
- ["D", "Kviatcovsky"],
- ["M M", "Romero"],
- ["L", "Balboa"],
- ["J", "Monteserin"],
- ["V", "Ritacco"],
- ["B", "Lopez"],
- ["C", "Sabio y Garc\u00eda"],
- ["A", "Garc\u00eda"],
- ["M", "Vescovo"],
- ["P G", "Montaner"],
- ["D", "Palmero"],
- ["M", "Del Carmen Sasiain"],
- ["S", "de la Barrera"]
+ ["Hyeeun", "Shin"],
+ ["Man Ho", "Kim"],
+ ["Su Jin", "Lee"],
+ ["Kyung-Han", "Lee"],
+ ["Mi-Jung", "Kim"],
+ ["Ji Sun", "Kim"],
+ ["Jin Whan", "Cho"]
],
- "publisher": "Clinical and experimental immunology",
- "issn": "1365-2249",
- "date": "2016-11-02",
- "abstract": "We have reported previously that T cells from patients with multi-drug-resistant tuberculosis (MDR-TB) express high levels of interleukin (IL)-17 in response to the MDR strain M (Haarlem family) of Mycobacterium tuberculosis (M. tuberculosis). Herein, we explore the pathways involved in the induction of Th17 cells in MDR-TB patients and healthy tuberculin reactors [purified protein derivative healthy donors (PPD",
+ "publisher": "Journal of clinical neurology (Seoul, Korea)",
+ "issn": "1738-6586",
+ "date": "2013-01-03",
+ "abstract": "Huntington's disease (HD) is an autosomal-dominant inherited neurodegenerative disorder. Genetic analysis of abnormal CAG expansion in the IT15 gene allows disease confirmation even in the preclinical stage. However, because there is no treatment to cure or delay the progression of this disease, monitoring of biological markers that predict progression is warranted.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27681197"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23346156"
},
{
- "id": "pmid:27740685",
+ "id": "pmid:23277128",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/27740685",
- "title": "Factors related to genetic testing in adults at risk for Huntington disease: the prospective Huntington at-risk observational study (PHAROS).",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23277128",
+ "title": "Study of the association of serotonin transporter triallelic 5-HTTLPR and STin2 VNTR polymorphisms with lithium prophylaxis response in bipolar disorder.",
"type": "article-journal",
- "doi": "10.1111/cge.12893",
+ "doi": "10.1097/ypg.0b013e32835d6fad",
"authors": [
- ["K A", "Quaid"],
- ["S W", "Eberly"],
- ["E", "Kayson-Rubin"],
- ["D", "Oakes"],
- ["I", "Shoulson"]
+ ["Hema", "Tharoor"],
+ ["Ananthapadmanabha", "Kotambail"],
+ ["Sanjeev", "Jain"],
+ ["Podila Satya Venkata Narasimha", "Sharma"],
+ ["Kapaettu", "Satyamoorthy"]
],
- "publisher": "Clinical genetics",
- "issn": "1399-0004",
- "date": "2016-11-24",
- "abstract": "Huntington disease (HD) is a late onset ultimately fatal neurodegenerative disorder caused by a cytosine-adenine-guanine ( CAG) triplet repeat expansion in the Huntingtin gene which was discovered in 1993. The PHAROS study is a unique observational study of 1001 individuals at risk for HD who had not been previously tested for HD and who had no plans to do so. In this cohort, 104 (10%) individuals changed their minds and chose to be tested during the course of the study but outside of the study protocol. Baseline behavioral scores, especially apathy, were more strongly associated with later genetic testing than motor and chorea scores, particularly among subjects with expanded CAG repeat length. In the CAG expanded group, those choosing to be tested were older and had more chorea and higher scores on the behavioral section of the unified Huntington's disease rating scale at baseline than those not choosing to be tested. Following genetic testing, 56% of subjects with CAG < 37 had less depression when compared to prior to testing, but depression generally stayed the same or increased for 64% of subjects in the expanded group. This finding suggests that approaches to testing must continue to be cautious, with appropriate medical, psychological and social support.",
+ "publisher": "Psychiatric genetics",
+ "issn": "1473-5873",
+ "date": "2013-04-01",
+ "abstract": "The 5-hydroxy tryptamine transporter (5-HTT) gene has been previously implicated in lithium response, but the roles of the triallelic 5-HTT linked promoter region (5-HTTLPR) and variable number tandem repeats in the second intron [serotonin transporter intron 2 (STin2)] have not been reported. We examined these polymorphisms in 122 patients with bipolar I disorder, among which 49 patients were classified as good responders, 49 as nonresponders, and 24 as partial responders to lithium prophylaxis. We observed significant variation in the genotype frequencies of STin2 polymorphism among the response groups (P=0.02). There was also a significant association of haplotype consisting of the S allele of 5-HTTLPR and 10 repeat allele of STin2 with lithium response (P=0.01) and no such relationship was found with 5-HTTLPR variants. Our data support preliminary information of a possible association of STin2 and its combined effect with 5-HTTLPR variants with lithium response and also suggest that lithium is likely to be more effective for patients carrying 5-HTT polymorphisms associated with reduced transcriptional activity.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27740685"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23277128"
},
{
- "id": "pmid:27689620",
+ "id": "pmid:25063431",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/27689620",
- "title": "Cellular Analysis of Silencing the\u00a0Huntington's Disease Gene Using AAV9\u00a0Mediated Delivery of Artificial Micro\u00a0RNA into the Striatum of\u00a0Q140/Q140\u00a0Mice.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25063431",
+ "title": "Preliminary analysis of Huntington's Disease in South Korea.",
"type": "article-journal",
- "doi": "10.3233/jhd-160215",
+ "doi": "10.3233/jhd-120040",
"authors": [
- ["Allison M", "Keeler"],
- ["Ellen", "Sapp"],
- ["Kathryn", "Chase"],
- ["Emily", "Sottosanti"],
- ["Eric", "Danielson"],
- ["Edith", "Pfister"],
- ["Lorelei", "Stoica"],
- ["Marian", "DiFiglia"],
- ["Neil", "Aronin"],
- ["Miguel", "Sena-Esteves"]
+ ["Chae Won", "Shin"],
+ ["Yoon Jae", "Choi"],
+ ["Manho", "Kim"],
+ ["Beom Seok", "Jeon"]
],
"publisher": "Journal of Huntington's disease",
- "issn": "1879-6400",
- "date": "2016-10-01",
- "abstract": "The genetic mutation in Huntington's disease (HD) is a\u00a0CAG repeat expansion in the coding region of the huntingtin (Htt) gene. RNAi strategies have proven effective in substantially down-regulating Htt mRNA in the striatum through delivery of siRNAs or viral vectors based on whole tissue assays, but the extent of htt mRNA lowering in individual neurons is unknown.",
+ "issn": "1879-6397",
+ "date": "2013-01-01",
+ "abstract": "There have been epidemiological studies of Huntington's disease (HD) in various populations and nations. Only a few studies describing clinical characteristics have been reported in Asia.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27689620"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25063431"
},
{
- "id": "pmid:27658206",
+ "id": "pmid:23157165",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/27658206",
- "title": "Polyglutamine Tract Expansion Increases S-Nitrosylation of Huntingtin and Ataxin-1.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23157165",
+ "title": "CAG/CTG repeats alter the affinity for the histone core and the positioning of DNA in the nucleosome.",
"type": "article-journal",
- "doi": "10.1371/journal.pone.0163359",
+ "doi": "10.1021/bi301416v",
"authors": [
- ["Chun-Lun", "Ni"],
- ["Divya", "Seth"],
- ["Fabio Vasconcelos", "Fonseca"],
- ["Liwen", "Wang"],
- ["Tsan Sam", "Xiao"],
- ["Phillip", "Gruber"],
- ["Man-Sun", "Sy"],
- ["Jonathan S", "Stamler"],
- ["Alan M", "Tartakoff"]
+ ["Catherine B", "Volle"],
+ ["Sarah", "Delaney"]
],
- "publisher": "PloS one",
- "issn": "1932-6203",
- "date": "2016-09-22",
- "abstract": "Expansion of the polyglutamine (polyQ) tract in the huntingtin (Htt) protein causes Huntington's disease (HD), a fatal inherited movement disorder linked to neurodegeneration in the striatum and cortex. S-nitrosylation and S-acylation of cysteine residues regulate many functions of cytosolic proteins. We therefore used a resin-assisted capture approach to identify these modifications in Htt. In contrast to many proteins that have only a single S-nitrosylation or S-acylation site, we identified sites along much of the length of Htt. Moreover, analysis of cells expressing full-length Htt or a large N-terminal fragment of Htt shows that polyQ expansion strongly increases Htt S-nitrosylation. This effect appears to be general since it is also observed in Ataxin-1, which causes spinocerebellar ataxia type 1 (SCA1) when its polyQ tract is expanded. Overexpression of nitric oxide synthase increases the S-nitrosylation of normal Htt and the frequency of conspicuous juxtanuclear inclusions of Htt N-terminal fragments in transfected cells. Taken together with the evidence that S-nitrosylation of Htt is widespread and parallels polyQ expansion, these subcellular changes show that S-nitrosylation affects the biology of this protein in vivo.",
+ "publisher": "Biochemistry",
+ "issn": "1520-4995",
+ "date": "2012-11-27",
+ "abstract": "Trinucleotide repeats (TNRs) occur throughout the genome, and their expansion has been linked to several neurodegenerative disorders, including Huntington's disease. TNRs have been studied using both oligonucleotides and plasmids; however, less is know about how repetitive DNA responds to genomic packaging. Here, we investigate the behavior of CAG/CTG repeats incorporated into nucleosome core particles, the most basic unit of chromatin packaging. To assess the general interaction between CAG/CTG repeats and the histone core, we determined the efficiency with which various TNR-containing DNA substrates form nucleosomes, revealing that even short CAG/CTG tracts are robust incorporators. However, the presence of the Huntington gene flanking sequence (htt) decreases the rate of incorporation. Enzymatic and chemical probing revealed repositioning of the DNA in the nucleosome as the number of CAG/CTG repeats increased, regardless of the flanking sequence. Notably, the periodicity of the repeat tract remained unchanged as a function of length and is consistently 10.7 bp per helical turn. In contrast, the periodicity of the nonrepetitive flanking sequence varies and is smaller than the repeat tract at ~10.0-10.5 bp per turn. Furthermore, while the CAG/CTG repeats remain as a canonical duplex in the nucleosome, nucleosome formation causes kinking in a secondary repeat tract in the htt gene, comprised of CCG/CGG repeats. This work highlights the innate ability of CAG/CTG repeats to incorporate and to position in nucleosomes and how that behavior is modulated by the htt flanking sequence. In addition, it illuminates the differences in packaging of healthy and diseased length repeat tracts within the genome.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27658206"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23157165"
},
{
- "id": "pmid:27639545",
+ "id": "pmid:23008174",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/27639545",
- "title": "In vivo proof-of-concept of removal of the huntingtin caspase cleavage motif-encoding exon 12 approach in the YAC128 mouse model of Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23008174",
+ "title": "Huntington's disease: how intermediate are intermediate repeat lengths?",
"type": "article-journal",
- "doi": "10.1016/j.biopha.2016.09.007",
+ "doi": "10.1002/mds.25172",
"authors": [
- ["Jo\u00e3o", "Casaca-Carreira"],
- ["Lodewijk J A", "Toonen"],
- ["Melvin M", "Evers"],
- ["Ali", "Jahanshahi"],
- ["Willeke M C", "van-Roon-Mom"],
- ["Yasin", "Temel"]
+ ["Ferdinando", "Squitieri"],
+ ["Joseph", "Jankovic"]
],
- "publisher": "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie",
- "issn": "1950-6007",
- "date": "2016-09-16",
- "abstract": "Huntington's disease (HD) is a progressive autosomal dominant disease, caused by a CAG repeat expansion in the HTT gene, resulting in an expanded polyglutamine stretch at the N-terminal of the huntingtin protein. An important event in HD pathogenesis appears to be the proteolysis of the mutant protein, which forms N-terminal huntingtin fragments. These fragments form insoluble aggregates and are found in nuclei and cytoplasm of affected neurons where they interfere with normal cell functioning. Important cleavage sites are encoded by exon 12 of HTT. A novel approach is Htt protein modification through exon skipping, which has recently been proven effective both in vitro and in vivo. Here we report proof-of-concept of AON 12.1 in vivo using the YAC128 mouse model of HD. Our results support and encourage future longitudinal studies exploring the therapeutic effects of sustained infusions in the YAC128 mouse model.",
+ "publisher": "Movement disorders : official journal of the Movement Disorder Society",
+ "issn": "1531-8257",
+ "date": "2012-09-24",
+ "abstract": "Huntington's disease (HD) is a devastating heredoneurodegenerative disorder associated with a wide variety of neurological and psychiatric symptoms caused by an expanded CAG repeat in the HTT gene. The expansion mutation in HTT is dominantly transmitted and codes for a protein named huntingtin (htt).",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27639545"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23008174"
},
{
- "id": "pmid:27540492",
+ "id": "pmid:22993450",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/27540492",
- "title": "Effects of Anthocyanins on CAG Repeat Instability and Behaviour in Huntington's Disease R6/1 Mice.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22993450",
+ "title": "The differential diagnosis of Huntington's disease-like syndromes: 'red flags' for the clinician.",
"type": "article-journal",
- "doi": "10.1371/currents.hd.58d04209ab6d5de0844db7ef5628ff67",
+ "doi": "10.1136/jnnp-2012-302532",
"authors": [
- ["Linda", "M\u00f8llersen"],
- ["Olve", "Moldestad"],
- ["Alexander D", "Rowe"],
- ["Anja", "Bj\u00f8lgerud"],
- ["Ingunn", "Holm"],
- ["Linda", "Tveter\u00e5s"],
- ["Arne", "Klungland"],
- ["Lars", "Retterst\u00f8l"]
+ ["Davide", "Martino"],
+ ["Maria", "Stamelou"],
+ ["Kailash P", "Bhatia"]
],
- "publisher": "PLoS currents",
- "issn": "2157-3999",
- "date": "2016-07-05",
- "abstract": "Huntington's disease (HD) is a progressive neurodegenerative disorder caused by CAG repeat expansions in the HTT gene. Somatic repeat expansion in the R6/1 mouse model of HD depends on mismatch repair and is worsened by base excision repair initiated by the 7,8-dihydroxy-8-oxoguanine-DNA glycosylase (Ogg1) or Nei-like 1 (Neil1). Ogg1 and Neil1 repairs common oxidative lesions.",
+ "publisher": "Journal of neurology, neurosurgery, and psychiatry",
+ "issn": "1468-330X",
+ "date": "2012-09-19",
+ "abstract": "A growing number of progressive heredodegenerative conditions mimic the presentation of Huntington's disease (HD). Differentiating among these HD-like syndromes is necessary when a patient with a combination of movement disorders, cognitive decline, behavioural abnormalities and progressive disease course proves negative to the genetic testing for HD causative mutations, that is, IT15 gene trinucleotide-repeat expansion. The differential diagnosis of HD-like syndromes is complex and may lead to unnecessary and costly investigations. We propose here a guide to this differential diagnosis focusing on a limited number of clinical features ('red flags') that can be identified through accurate clinical examination, collection of historical data and a few routine ancillary investigations. These features include the ethnic background of the patient, the involvement of the facio-bucco-lingual and cervical district by the movement disorder, the co-occurrence of cerebellar features and seizures, the presence of peculiar gait patterns and eye movement abnormalities, and an atypical progression of illness. Additional help may derive from the cognitive-behavioural presentation of the patient, as well as by a restricted number of ancillary investigations, mainly MRI and routine blood tests. These red flags should be constantly updated as the phenotypic characterisation and identification of more reliable diagnostic markers for HD-like syndromes progress over the following years.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27540492"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22993450"
},
{
- "id": "pmid:27477323",
+ "id": "pmid:22985800",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/27477323",
- "title": "Natural variation in sensory-motor white matter organization influences manifestations of Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22985800",
+ "title": "Abnormal apocrine secretory cell mitochondria in a Huntington disease patient.",
"type": "article-journal",
- "doi": "10.1002/hbm.23332",
+ "doi": "10.1016/j.jns.2012.08.034",
"authors": [
- ["Michael", "Orth"],
- ["Sarah", "Gregory"],
- ["Rachael I", "Scahill"],
- ["Isabella Sm", "Mayer"],
- ["Lora", "Minkova"],
- ["Stefan", "Kl\u00f6ppel"],
- ["Kiran K", "Seunarine"],
- ["Lara", "Boyd"],
- ["Beth", "Borowsky"],
- ["Ralf", "Reilmann"],
- ["G", "Bernhard Landwehrmeyer"],
- ["Blair R", "Leavitt"],
- ["Raymund Ac", "Roos"],
- ["Alexandra", "Durr"],
- ["Geraint", "Rees"],
- ["John C", "Rothwell"],
- ["Douglas", "Langbehn"],
- ["Sarah J", "Tabrizi"]
+ ["Christos", "Sidiropoulos"],
+ ["Peter", "LeWitt"],
+ ["Ken", "Hashimoto"]
],
- "publisher": "Human brain mapping",
- "issn": "1097-0193",
- "date": "2016-08-01",
- "abstract": "While the HTT CAG-repeat expansion mutation causing Huntington's disease (HD) is highly correlated with the rate of pathogenesis leading to disease onset, considerable variance in age-at-onset remains unexplained. Therefore, other factors must influence the pathogenic process. We asked whether these factors were related to natural biological variation in the sensory-motor system. In 243 participants (96 premanifest and 35 manifest HD; 112 controls), sensory-motor structural MRI, tractography, resting-state fMRI, electrophysiology (including SEP amplitudes), motor score ratings, and grip force as sensory-motor performance were measured. Following individual modality analyses, we used principal component analysis (PCA) to identify patterns associated with sensory-motor performance, and manifest versus premanifest HD discrimination. We did not detect longitudinal differences over 12 months. PCA showed a pattern of loss of caudate, grey and white matter volume, cortical thickness in premotor and sensory cortex, and disturbed diffusivity in sensory-motor white matter tracts that was connected to CAG repeat length. Two further major principal components appeared in controls and HD individuals indicating that they represent natural biological variation unconnected to the HD mutation. One of these components did not influence HD while the other non-CAG-driven component of axial versus radial diffusivity contrast in white matter tracts were associated with sensory-motor performance and manifest HD. The first component reflects the expected CAG expansion effects on HD pathogenesis. One non-CAG-driven component reveals an independent influence on pathogenesis of biological variation in white matter tracts and merits further investigation to delineate the underlying mechanism and the potential it offers for disease modification. Hum Brain Mapp 37:4615-4628, 2016. \u00a9 2016 Wiley Periodicals, Inc.",
+ "publisher": "Journal of the neurological sciences",
+ "issn": "1878-5883",
+ "date": "2012-09-15",
+ "abstract": "Over two decades, a 42-year old woman experienced the gradual onset of choreic involuntary movements, dystonia, and tics. Decreased caudate nucleus metabolism on 2-deoxyglucose PET scan and a heterozygous 49-CAG repeat expansion within the HTT gene established the diagnosis of HD, although no other family history was known. An axillary skin biopsy revealed a distinctive abnormality of mitochondria limited to the apocrine secretory cells on electron microscopy. All mitochondria were transformed into rounded structures with disrupted cristae and prominent myelin figures; many were enlarged up to 4 times the normal. Cytoplasm of apocrine secretory cells showed an abundance of lipid vacuoles, empty vesicles, and dense bodies. Biopsied skeletal muscle histology (light microscopy) was normal, as was a mitochondrial metabolism study. Biopsies from other HD patients have shown similar mitochondrial changes in cerebral neurons, muscle, fibroblasts, and lymphoblasts, adding to evidence for a systemic disturbance of mitochondria in HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27477323"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22985800"
},
{
- "id": "pmid:27376585",
+ "id": "pmid:22814437",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/27376585",
- "title": "Large-scale phenome analysis defines a behavioral signature for Huntington's disease genotype in mice.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22814437",
+ "title": "Replacement of huntingtin exon 1 by trans-splicing.",
"type": "article-journal",
- "doi": "10.1038/nbt.3587",
+ "doi": "10.1007/s00018-012-1083-5",
"authors": [
- ["Vadim", "Alexandrov"],
- ["Dani", "Brunner"],
- ["Liliana B", "Menalled"],
- ["Andrea", "Kudwa"],
- ["Judy", "Watson-Johnson"],
- ["Matthew", "Mazzella"],
- ["Ian", "Russell"],
- ["Melinda C", "Ruiz"],
- ["Justin", "Torello"],
- ["Emily", "Sabath"],
- ["Ana", "Sanchez"],
- ["Miguel", "Gomez"],
- ["Igor", "Filipov"],
- ["Kimberly", "Cox"],
- ["Mei", "Kwan"],
- ["Afshin", "Ghavami"],
- ["Sylvie", "Ramboz"],
- ["Brenda", "Lager"],
- ["Vanessa C", "Wheeler"],
- ["Jeff", "Aaronson"],
- ["Jim", "Rosinski"],
- ["James F", "Gusella"],
- ["Marcy E", "MacDonald"],
- ["David", "Howland"],
- ["Seung", "Kwak"]
+ ["Hansj\u00f6rg", "Rindt"],
+ ["Pei-Fen", "Yen"],
+ ["Christina N", "Thebeau"],
+ ["Troy S", "Peterson"],
+ ["Gary A", "Weisman"],
+ ["Christian L", "Lorson"]
],
- "publisher": "Nature biotechnology",
- "issn": "1546-1696",
- "date": "2016-07-04",
- "abstract": "Rapid technological advances for the frequent monitoring of health parameters have raised the intriguing possibility that an individual's genotype could be predicted from phenotypic data alone. Here we used a machine learning approach to analyze the phenotypic effects of polymorphic mutations in a mouse model of Huntington's disease that determine disease presentation and age of onset. The resulting model correlated variation across 3,086 behavioral traits with seven different CAG-repeat lengths in the huntingtin gene (Htt). We selected behavioral signatures for age and CAG-repeat length that most robustly distinguished between mouse lines and validated the model by correctly predicting the repeat length of a blinded mouse line. Sufficient discriminatory power to accurately predict genotype required combined analysis of >200 phenotypic features. Our results suggest that autosomal dominant disease-causing mutations could be predicted through the use of subtle behavioral signatures that emerge in large-scale, combinatorial analyses. Our work provides an open data platform that we now share with the research community to aid efforts focused on understanding the pathways that link behavioral consequences to genetic variation in Huntington's disease.",
+ "publisher": "Cellular and molecular life sciences : CMLS",
+ "issn": "1420-9071",
+ "date": "2012-07-20",
+ "abstract": "Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder caused by polyglutamine expansion in the amino-terminus of huntingtin (HTT). HD offers unique opportunities for promising RNA-based therapeutic approaches aimed at reducing mutant HTT expression, since the HD mutation is considered to be a \"gain-of-function\" mutation. Allele-specific strategies that preserve expression from the wild-type allele and reduce the levels of mutant protein would be of particular interest. Here, we have conducted proof-of-concept studies to demonstrate that spliceosome-mediated trans-splicing is a viable molecular strategy to specifically repair the HTT allele. We employed a dual plasmid transfection system consisting of a pre-mRNA trans-splicing module (PTM) containing HTT exon 1 and a HTT minigene to demonstrate that HTT exon 1 can be replaced in trans. We detected the presence of the trans-spliced RNA in which PTM exon 1 was correctly joined to minigene exons 2 and 3. Furthermore, exon 1 from the PTM was trans-spliced to the endogenous HTT pre-mRNA in cultured cells as well as disease-relevant models, including HD patient fibroblasts and primary neurons from a previously described HD mouse model. These results suggest that the repeat expansion of HTT can be repaired successfully not only in the context of synthetic minigenes but also within the context of HD neurons. Therefore, pre-mRNA trans-splicing may be a promising approach for the treatment of HD and other dominant genetic disorders.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27376585"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22814437"
},
{
- "id": "pmid:27335079",
+ "id": "pmid:22803944",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/27335079",
- "title": "Identification of Novel Microsatellite Markers <1 Mb from the HTT CAG Repeat and Development of a Single-Tube Tridecaplex PCR Panel of Highly Polymorphic Markers for Preimplantation Genetic Diagnosis of Huntington Disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22803944",
+ "title": "Initiation of 8-oxoguanine base excision repair within trinucleotide tandem repeats.",
"type": "article-journal",
- "doi": "10.1373/clinchem.2016.255711",
+ "doi": "10.1134/s0006297912030054",
"authors": [
- ["Mingjue", "Zhao"],
- ["Min", "Chen"],
- ["Caroline G", "Lee"],
- ["Samuel S", "Chong"]
+ ["A G", "Derevyanko"],
+ ["A V", "Endutkin"],
+ ["A A", "Ishchenko"],
+ ["M K", "Saparbaev"],
+ ["D O", "Zharkov"]
],
- "publisher": "Clinical chemistry",
- "issn": "1530-8561",
- "date": "2016-06-22",
- "abstract": "Preimplantation genetic diagnosis (PGD) of Huntington disease (HD) generally employs linkage analysis of flanking microsatellite markers to complement direct mutation testing, as well as for exclusion testing. Thus far, only 10 linked markers have been developed for use in HD PGD, with a maximum of 3 markers coamplified successfully. We aimed to develop a single-tube multiplex PCR panel of highly polymorphic markers to simplify HD PGD.",
+ "publisher": "Biochemistry. Biokhimiia",
+ "issn": "1608-3040",
+ "date": "2012-03-01",
+ "abstract": "Trinucleotide repeat expansion provides a molecular basis for several devastating neurodegenerative diseases. In particular, expansion of a CAG run in the human HTT gene causes Huntington's disease. One of the main reasons for triplet repeat expansion in somatic cells is base excision repair (BER), involving damaged base excision and repair DNA synthesis that may be accompanied by expansion of the repaired strand due to formation of noncanonical DNA structures. We have analyzed the kinetics of excision of a ubiquitously found oxidized purine base, 8-oxoguanine (oxoG), by DNA glycosylase OGG1 from the substrates containing a CAG run flanked by AT-rich sequences. The values of k(2) rate constant for the removal of oxoG from triplets in the middle of the run were higher than for oxoG at the flanks of the run. The value of k(3) rate constant dropped starting from the third CAG-triplet in the run and remained stable until the 3'-terminal triplet, where it decreased even more. In nuclear extracts, the profile of oxoG removal rate along the run resembled the profile of k(2) constant, suggesting that the reaction rate in the extracts is limited by base excision. The fully reconstituted BER was efficient with all substrates unless oxoG was near the 3'-flank of the run, interfering with the initiation of the repair. DNA polymerase \u03b2 was able to perform a strand-displacement DNA synthesis, which may be important for CAG run expansion initiated by BER.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27335079"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22803944"
},
{
- "id": "pmid:27271685",
+ "id": "pmid:22786682",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/27271685",
- "title": "Folding Landscape of Mutant Huntingtin Exon1: Diffusible Multimers, Oligomers and Fibrils, and No Detectable Monomer.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22786682",
+ "title": "PGC-1\u03b1 rescues Huntington's disease proteotoxicity by preventing oxidative stress and promoting TFEB function.",
"type": "article-journal",
- "doi": "10.1371/journal.pone.0155747",
+ "doi": "10.1126/scitranslmed.3003799",
"authors": [
- ["Bankanidhi", "Sahoo"],
- ["Irene", "Arduini"],
- ["Kenneth W", "Drombosky"],
- ["Ravindra", "Kodali"],
- ["Laurie H", "Sanders"],
- ["J Timothy", "Greenamyre"],
- ["Ronald", "Wetzel"]
+ ["Taiji", "Tsunemi"],
+ ["Travis D", "Ashe"],
+ ["Bradley E", "Morrison"],
+ ["Kathryn R", "Soriano"],
+ ["Jonathan", "Au"],
+ ["Ruben A V\u00e1zquez", "Roque"],
+ ["Eduardo R", "Lazarowski"],
+ ["Vincent A", "Damian"],
+ ["Eliezer", "Masliah"],
+ ["Albert R", "La Spada"]
],
- "publisher": "PloS one",
- "issn": "1932-6203",
- "date": "2016-06-06",
- "abstract": "Expansion of the polyglutamine (polyQ) track of the Huntingtin (HTT) protein above 36 is associated with a sharply enhanced risk of Huntington's disease (HD). Although there is general agreement that HTT toxicity resides primarily in N-terminal fragments such as the HTT exon1 protein, there is no consensus on the nature of the physical states of HTT exon1 that are induced by polyQ expansion, nor on which of these states might be responsible for toxicity. One hypothesis is that polyQ expansion induces an alternative, toxic conformation in the HTT exon1 monomer. Alternative hypotheses posit that the toxic species is one of several possible aggregated states. Defining the nature of the toxic species is particularly challenging because of facile interconversion between physical states as well as challenges to identifying these states, especially in vivo. Here we describe the use of fluorescence correlation spectroscopy (FCS) to characterize the detailed time and repeat length dependent self-association of HTT exon1-like fragments both with chemically synthesized peptides in vitro and with cell-produced proteins in extracts and in living cells. We find that, in vitro, mutant HTT exon1 peptides engage in polyQ repeat length dependent dimer and tetramer formation, followed by time dependent formation of diffusible spherical and fibrillar oligomers and finally by larger, sedimentable amyloid fibrils. For expanded polyQ HTT exon1 expressed in PC12 cells, monomers are absent, with tetramers being the smallest molecular form detected, followed in the incubation time course by small, diffusible aggregates at 6-9 hours and larger, sedimentable aggregates that begin to build up at 12 hrs. In these cell cultures, significant nuclear DNA damage appears by 6 hours, followed at later times by caspase 3 induction, mitochondrial dysfunction, and cell death. Our data thus defines limits on the sizes and concentrations of different physical states of HTT exon1 along the reaction profile in the context of emerging cellular distress. The data provide some new candidates for the toxic species and some new reservations about more well-established candidates. Compared to other known markers of HTT toxicity, nuclear DNA damage appears to be a relatively early pathological event.",
+ "publisher": "Science translational medicine",
+ "issn": "1946-6242",
+ "date": "2012-07-11",
+ "abstract": "Huntington's disease (HD) is caused by CAG repeat expansions in the huntingtin (htt) gene, yielding proteins containing polyglutamine repeats that become misfolded and resist degradation. Previous studies demonstrated that mutant htt interferes with transcriptional programs coordinated by the peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3) coactivator 1\u03b1 (PGC-1\u03b1), a regulator of mitochondrial biogenesis and oxidative stress. We tested whether restoration of PGC-1\u03b1 could ameliorate the symptoms of HD in a mouse model. We found that PGC-1\u03b1 induction virtually eliminated htt protein aggregation and ameliorated HD neurodegeneration in part by attenuating oxidative stress. PGC-1\u03b1 promoted htt turnover and the elimination of protein aggregates by activating transcription factor EB (TFEB), a master regulator of the autophagy-lysosome pathway. TFEB alone was capable of reducing htt aggregation and neurotoxicity, placing PGC-1\u03b1 upstream of TFEB and identifying these two molecules as important therapeutic targets in HD and potentially other neurodegenerative disorders caused by protein misfolding.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27271685"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22786682"
},
{
- "id": "pmid:27221610",
+ "id": "pmid:22668780",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/27221610",
- "title": "Altered Expression of the Long Noncoding RNA NEAT1 in Huntington's Disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22668780",
+ "title": "Mitigation of augmented extrasynaptic NMDAR signaling and apoptosis in cortico-striatal co-cultures from Huntington's disease mice.",
"type": "article-journal",
- "doi": "10.1007/s12035-016-9928-9",
+ "doi": "10.1016/j.nbd.2012.05.013",
"authors": [
- ["Jun-Sang", "Sunwoo"],
- ["Soon-Tae", "Lee"],
- ["Wooseok", "Im"],
- ["Mijung", "Lee"],
- ["Jung-Ick", "Byun"],
- ["Keun-Hwa", "Jung"],
- ["Kyung-Il", "Park"],
- ["Ki-Young", "Jung"],
- ["Sang Kun", "Lee"],
- ["Kon", "Chu"],
- ["Manho", "Kim"]
+ ["Austen J", "Milnerwood"],
+ ["Alexandra M", "Kaufman"],
+ ["Marja D", "Sepers"],
+ ["Clare M", "Gladding"],
+ ["Lily", "Zhang"],
+ ["Liang", "Wang"],
+ ["Jing", "Fan"],
+ ["Ainsley", "Coquinco"],
+ ["Joy Yi", "Qiao"],
+ ["Hwan", "Lee"],
+ ["Yu Tian", "Wang"],
+ ["Max", "Cynader"],
+ ["Lynn A", "Raymond"]
],
- "publisher": "Molecular neurobiology",
- "issn": "1559-1182",
- "date": "2016-05-25",
- "abstract": "Huntington's disease (HD) is a devastating neurodegenerative disease caused by cytosine-adenine-guanine trinucleotide repeat expansion in the huntingtin gene. Growing evidence supports the regulatory functions of long noncoding RNAs (lncRNAs) in the disease process, but little is known about the association between lncRNAs and neuronal death in HD. Here, we evaluated the altered expression profiles of lncRNA in HD by using microarrays. Among dysregulated lncRNAs, we focused on the upregulation of nuclear paraspeckle assembly transcript 1 (NEAT1). Quantitative PCR analysis validated increased NEAT1 levels in the R6/2 mouse brain as well as the human HD postmortem brain. To determine the biological effects of NEAT1 on neuronal survival, neuro2A cells were transfected with the NEAT1 short isoform vector and were subjected to H",
+ "publisher": "Neurobiology of disease",
+ "issn": "1095-953X",
+ "date": "2012-06-02",
+ "abstract": "We recently reported evidence for disturbed synaptic versus extrasynaptic NMDAR transmission in the early pathogenesis of Huntington's disease (HD), a late-onset neurodegenerative disorder caused by CAG repeat expansion in the gene encoding huntingtin. Studies in glutamatergic cells indicate that synaptic NMDAR transmission increases phosphorylated cyclic-AMP response element binding protein (pCREB) levels and drives neuroprotective gene transcription, whereas extrasynaptic NMDAR activation reduces pCREB and promotes cell death. By generating striatal and cortical neuronal co-cultures to investigate the glutamatergic innervation of striatal neurons, we demonstrate that dichotomous synaptic and extrasynaptic NMDAR signaling also occurs in GABAergic striatal medium-sized spiny neurons (MSNs), which are acutely vulnerable in HD. Further, we show that wild-type (WT) and HD transgenic YAC128 MSNs co-cultured with cortical cells have similar levels of glutamatergic synapses, synaptic NMDAR currents and synaptic GluN2B and GluN2A subunit-containing NMDARs. However, NMDAR whole-cell, and especially extrasynaptic, current is elevated in YAC128 MSNs. Moreover, GluN2B subunit-containing NMDAR surface expression is markedly increased, irrespective of whether or not the co-cultured cortical cells express mutant huntingtin. The data suggest that MSN cell-autonomous increases in extrasynaptic NMDARs are driven by the HD mutation. Consistent with these results, we find that extrasynaptic NMDAR-induced pCREB reductions and apoptosis are also augmented in YAC128 MSNs. Moreover, both NMDAR-mediated apoptosis and CREB-off signaling are blocked by co-application of either memantine or the GluN2B subunit-selective antagonist ifenprodil in YAC128 MSNs. GluN2A-subunit-selective concentrations of the antagonist NVP-AAM077 did not reduce cell death in either genotype. Cortico-striatal co-cultures provide an in vitro model system in which to better investigate striatal neuronal dysfunction in disease than mono-cultured striatal cells. Results from the use of this system, which partially recapitulates the cortico-striatal circuit and is amenable to acute genetic and pharmacological manipulations, suggest that pathophysiological NMDAR signaling is an intrinsic frailty in HD MSNs that can be successfully targeted by pharmacological interventions.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27221610"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22668780"
},
{
- "id": "pmid:27182645",
+ "id": "pmid:22649062",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/27182645",
- "title": "DNA Methylation Leads to DNA Repair Gene Down-Regulation and Trinucleotide Repeat Expansion in Patient-Derived Huntington Disease Cells.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22649062",
+ "title": "Brain metabolite alterations and cognitive dysfunction in early Huntington's disease.",
"type": "article-journal",
- "doi": "10.1016/j.ajpath.2016.03.014",
+ "doi": "10.1002/mds.25010",
"authors": [
- ["Peter A", "Mollica"],
- ["John A", "Reid"],
- ["Roy C", "Ogle"],
- ["Patrick C", "Sachs"],
- ["Robert D", "Bruno"]
+ ["Paul G", "Unschuld"],
+ ["Richard A E", "Edden"],
+ ["Aaron", "Carass"],
+ ["Xinyang", "Liu"],
+ ["Megan", "Shanahan"],
+ ["Xin", "Wang"],
+ ["Kenichi", "Oishi"],
+ ["Jason", "Brandt"],
+ ["Susan S", "Bassett"],
+ ["Graham W", "Redgrave"],
+ ["Russell L", "Margolis"],
+ ["Peter C M", "van Zijl"],
+ ["Peter B", "Barker"],
+ ["Christopher A", "Ross"]
],
- "publisher": "The American journal of pathology",
- "issn": "1525-2191",
- "date": "2016-05-13",
- "abstract": "Huntington disease (HD) is an autosomal dominantly inherited disease that exhibits genetic anticipation of affected progeny due to expansions of a trinucleotide repeat (TNR) region within the HTT gene. DNA repair machinery is a known effector of TNR instability; however, the specific defects in HD cells that lead to TNR expansion are unknown. We hypothesized that HD cells would be deficient in DNA repair gene expression. To test this hypothesis, we analyzed expression of select DNA repair genes involved in mismatch/loop-out repair (APEX1, BRCA1, RPA1, and RPA3) in patient-derived HD cells and found each was consistently down-regulated relative to wild-type samples taken from unaffected individuals in the same family. Rescue of DNA repair gene expression by 5-azacytidine treatment identified DNA methylation as a mediator of DNA repair gene expression deficiency. Bisulfite sequencing confirmed hypermethylation of the APEX1 promoter region in HD cells relative to control, as well as 5-azacytidine-induced hypomethylation. 5-Azacytidine treatments also resulted in stabilization of TNR expansion within the mutant HTT allele during long-term culture of HD cells. Our findings indicate that DNA methylation leads to DNA repair down-regulation and TNR instability in mitotically active HD cells and offer a proof of principle that epigenetic interventions can curb TNR expansions.",
+ "publisher": "Movement disorders : official journal of the Movement Disorder Society",
+ "issn": "1531-8257",
+ "date": "2012-05-30",
+ "abstract": "Huntington's disease (HD) is a neurodegenerative disorder characterized by early cognitive decline that progresses at later stages to dementia and severe movement disorder. HD is caused by a cytosine-adenine-guanine triplet-repeat expansion mutation in the Huntingtin gene, allowing early diagnosis by genetic testing. This study aimed to identify the relationship of N-acetylaspartate and other brain metabolites to cognitive function in HD-mutation carriers by using high-field-strength magnetic resonance spectroscopy (MRS) at 7 Tesla. Twelve individuals with the HD mutation in premanifest or early-stage disease versus 12 healthy controls underwent (1)H magnetic resonance spectroscopy (7.2 mL voxel in the posterior cingulate cortex) at 7 Tesla, and also T1-weighted structural magnetic resonance imaging. All participants received standardized tests of cognitive functioning including the Montreal Cognitive Assessment and standardized quantified neurological examination within an hour before scanning. Individuals with the HD mutation had significantly lower posterior cingulate cortex N-acetylaspartate (-9.6%, P = .02) and glutamate (-10.1%, P = .02) levels than did controls. In contrast, in this small group, measures of brain morphology including striatal and ventricle volumes did not differ significantly. Linear regression with Montreal Cognitive Assessment scores revealed significant correlations with N-acetylaspartate (r(2) = 0.50, P = .01) and glutamate (NAA) (r(2) = 0.64, P = .002) in HD subjects. Our data suggest a relationship between reduced N-acetylaspartate and glutamate levels in the posterior cingulate cortex with cognitive decline in the early stages of HD. N-acetylaspartate and glutamate magnetic resonance spectroscopy signals of the posterior cingulate cortex region may serve as potential biomarkers of disease progression or treatment outcome in HD and other neurodegenerative disorders with early cognitive dysfunction, when structural brain changes are still minor.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27182645"
-},
-{
- "id": "pmid:27080129",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/27080129",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:27080129']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22649062"
},
{
- "id": "pmid:27031731",
+ "id": "pmid:22623107",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/27031731",
- "title": "Delayed Onset and Reduced Cognitive Deficits through Pre-Conditioning with 3-Nitropropionic Acid is Dependent on Sex and CAG Repeat Length in the R6/2 Mouse Model of Huntington's Disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22623107",
+ "title": "Mass spectrometric identification of novel posttranslational modification sites in Huntingtin.",
"type": "article-journal",
- "doi": "10.3233/jhd-160189",
+ "doi": "10.1002/pmic.201100380",
"authors": [
- ["Elizabeth A", "Skillings"],
- ["A Jennifer", "Morton"]
+ ["Gaofeng", "Dong"],
+ ["Eduardo", "Callegari"],
+ ["Christian J", "Gloeckner"],
+ ["Marius", "Ueffing"],
+ ["Hongmin", "Wang"]
],
- "publisher": "Journal of Huntington's disease",
- "issn": "1879-6400",
- "date": "2016-01-01",
- "abstract": "Impairments in energy metabolism are implicated in Huntington's disease (HD) pathogenesis. Reduced levels of the mitochondrial enzyme succinate dehydrogenase (SDH), the main element of complex II, are observed post mortem in the brains of HD patients, and energy metabolism defects have been identified in both presymptomatic and symptomatic HD patients.",
+ "publisher": "Proteomics",
+ "issn": "1615-9861",
+ "date": "2012-06-01",
+ "abstract": "Huntington's disease (HD) is caused by a CAG triplet repeat expansion in exon 1 of the Huntingtin (Htt) gene, encoding an abnormal expanded polyglutamine (polyQ) tract that confers toxicity to the mutant Htt (mHtt) protein. Recent data suggest that posttranslational modifications of mHtt modulate its cytotoxicity. To further understand the cytotoxic mechanisms of mHtt, we have generated HEK293 cell models stably expressing Strep- and FLAG-tagged Htt containing either 19Q (wild-type Htt), 55Q (mHtt), or 94Q (mHtt) repeats. Following tandem affinity purification, the tagged Htt and associated proteins were subjected to tandem mass spectrometry or 2D nano-LC tandem mass spectrometry and several novel modification sites of mHtt containing 55Q or 94Q were identified. These were phosphorylation sites located at Ser431 and Ser432, and ubiquitination site located at Lys444. The two phosphorylation sites were confirmed by Western blot analysis using phosphorylation site-specific antibodies. In addition, prevention of phosphorylation at the two serine sites altered mHtt toxicity and accumulation. These modifications of mHtt may provide novel therapeutic targets for effective treatment of the disorder.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27031731"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22623107"
},
{
- "id": "pmid:27003665",
+ "id": "pmid:22580959",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/27003665",
- "title": "Does the Mutant CAG Expansion in Huntingtin mRNA Interfere with Exonucleolytic Cleavage of its First Exon?",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22580959",
+ "title": "Deregulation of BRCA1 leads to impaired spatiotemporal dynamics of \u03b3-H2AX and DNA damage responses in Huntington's disease.",
"type": "article-journal",
- "doi": "10.3233/jhd-150183",
+ "doi": "10.1007/s12035-012-8274-9",
"authors": [
- ["Wanzhao", "Liu"],
- ["Edith L", "Pfister"],
- ["Lori A", "Kennington"],
- ["Kathryn O", "Chase"],
- ["Christian", "Mueller"],
- ["Marian", "DiFiglia"],
- ["Neil", "Aronin"]
+ ["Gye Sun", "Jeon"],
+ ["Ki Yoon", "Kim"],
+ ["Yu Jin", "Hwang"],
+ ["Min-Kyung", "Jung"],
+ ["Sungkwan", "An"],
+ ["Mutsuko", "Ouchi"],
+ ["Toru", "Ouchi"],
+ ["Neil", "Kowall"],
+ ["Junghee", "Lee"],
+ ["Hoon", "Ryu"]
],
- "publisher": "Journal of Huntington's disease",
- "issn": "1879-6400",
- "date": "2016-01-01",
- "abstract": "Silencing mutant huntingtin mRNA by RNA interference (RNAi) is a therapeutic strategy for Huntington's disease. RNAi induces specific endonucleolytic cleavage of the target HTT mRNA, followed by exonucleolytic processing of the cleaved mRNA fragments.",
+ "publisher": "Molecular neurobiology",
+ "issn": "1559-1182",
+ "date": "2012-05-13",
+ "abstract": "Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder of mid-life onset characterized by involuntary movements and progressive cognitive decline caused by a CAG repeat expansion in exon 1 of the Huntingtin (Htt) gene. Neuronal DNA damage is one of the major features of neurodegeneration in HD, but it is not known how it arises or relates to the triplet repeat expansion mutation in the Htt gene. Herein, we found that imbalanced levels of non-phosphorylated and phosphorylated BRCA1 contribute to the DNA damage response in HD. Notably, nuclear foci of \u03b3-H2AX, the molecular component that recruits various DNA damage repair factors to damage sites including BRCA1, were deregulated when DNA was damaged in HD cell lines. BRCA1 specifically interacted with \u03b3-H2AX via the BRCT domain, and this association was reduced in HD. BRCA1 overexpression restored \u03b3-H2AX level in the nucleus of HD cells, while BRCA1 knockdown reduced the spatiotemporal propagation of \u03b3-H2AX foci to the nucleoplasm. The deregulation of BRCA1 correlated with an abnormal nuclear distribution of \u03b3-H2AX in striatal neurons of HD transgenic (R6/2) mice and BRCA1(+/-) mice. Our data indicate that BRCA1 is required for the efficient focal recruitment of \u03b3-H2AX to the sites of neuronal DNA damage. Taken together, our results show that BRCA1 directly modulates the spatiotemporal dynamics of \u03b3-H2AX upon genotoxic stress and serves as a molecular maker for neuronal DNA damage response in HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27003665"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22580959"
},
{
- "id": "pmid:26982737",
+ "id": "pmid:22580459",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26982737",
- "title": "Genomic Instability Associated with p53 Knockdown in the Generation of Huntington's Disease Human Induced Pluripotent Stem Cells.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22580459",
+ "title": "Huntingtin protein interactions altered by polyglutamine expansion as determined by quantitative proteomic analysis.",
"type": "article-journal",
- "doi": "10.1371/journal.pone.0150372",
+ "doi": "10.4161/cc.20423",
"authors": [
- ["Andrew M", "Tidball"],
- ["M Diana", "Neely"],
- ["Reed", "Chamberlin"],
- ["Asad A", "Aboud"],
- ["Kevin K", "Kumar"],
- ["Bingying", "Han"],
- ["Miles R", "Bryan"],
- ["Michael", "Aschner"],
- ["Kevin C", "Ess"],
- ["Aaron B", "Bowman"]
+ ["Tamara", "Ratovitski"],
+ ["Ekaterine", "Chighladze"],
+ ["Nicolas", "Arbez"],
+ ["Tatiana", "Boronina"],
+ ["Shelley", "Herbrich"],
+ ["Robert N", "Cole"],
+ ["Christopher A", "Ross"]
],
- "publisher": "PloS one",
- "issn": "1932-6203",
- "date": "2016-03-16",
- "abstract": "Alterations in DNA damage response and repair have been observed in Huntington's disease (HD). We generated induced pluripotent stem cells (iPSC) from primary dermal fibroblasts of 5 patients with HD and 5 control subjects. A significant fraction of the HD iPSC lines had genomic abnormalities as assessed by karyotype analysis, while none of our control lines had detectable genomic abnormalities. We demonstrate a statistically significant increase in genomic instability in HD cells during reprogramming. We also report a significant association with repeat length and severity of this instability. Our karyotypically normal HD iPSCs also have elevated ATM-p53 signaling as shown by elevated levels of phosphorylated p53 and H2AX, indicating either elevated DNA damage or hypersensitive DNA damage signaling in HD iPSCs. Thus, increased DNA damage responses in the HD genotype is coincidental with the observed chromosomal aberrations. We conclude that the disease causing mutation in HD increases the propensity of chromosomal instability relative to control fibroblasts specifically during reprogramming to a pluripotent state by a commonly used episomal-based method that includes p53 knockdown.",
+ "publisher": "Cell cycle (Georgetown, Tex.)",
+ "issn": "1551-4005",
+ "date": "2012-05-15",
+ "abstract": "Huntington disease (HD) is a neurodegenerative disorder caused by an expansion of a polyglutamine repeat within the HD gene product, huntingtin. Huntingtin, a large (347 kDa) protein containing multiple HEAT repeats, acts as a scaffold for protein-protein interactions. Huntingtin-induced toxicity is believed to be mediated by a conformational change in expanded huntingtin, leading to protein misfolding and aggregation, aberrant protein interactions and neuronal cell death. While many non-systematic studies of huntingtin interactions have been reported, they were not designed to identify and quantify the changes in the huntingtin interactome induced by polyglutamine expansion. We used tandem affinity purification and quantitative proteomics to compare and quantify interactions of normal or expanded huntingtin isolated from a striatal cell line. We found that proteins preferentially interacting with expanded huntingtin are enriched for intrinsically disordered proteins, consistent with previously suggested roles of such proteins in neurodegenerative disorders. Our functional analysis indicates that proteins related to energy production, protein trafficking, RNA post-transcriptional modifications and cell death were significantly enriched among preferential interactors of expanded huntingtin. Expanded huntingtin interacted with many mitochondrial proteins, including AIFM1, consistent with a role for mitochondrial dysfunction in HD. Furthermore, expanded huntingtin interacted with the stress granule-associated proteins Caprin-1 and G3BP and redistributed to RNA stress granules under ER-stress conditions. These data demonstrate that a number of key cellular functions and networks may be disrupted by abnormal interactions of expanded huntingtin and highlight proteins and pathways that may be involved in HD cellular pathogenesis and that may serve as therapeutic targets.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26982737"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22580459"
},
{
- "id": "pmid:26958025",
+ "id": "pmid:22542623",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26958025",
- "title": "Clinical and genetic data of Huntington disease in Moroccan patients.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22542623",
+ "title": "Deficient Rab11 activity underlies glucose hypometabolism in primary neurons of Huntington's disease mice.",
"type": "article-journal",
- "doi": "10.4314/ahs.v15i4.23",
+ "doi": "10.1016/j.bbrc.2012.04.070",
"authors": [
- ["Ahmed", "Bouhouche"],
- ["Wafaa", "Regragui"],
- ["Hind", "Lamghari"],
- ["Khadija", "Khaldi"],
- ["Nazha", "Birouk"],
- ["Safaa", "Lytim"],
- ["Soufiane", "Bellamine"],
- ["Yamna", "Kriouile"],
- ["Naima", "Bouslam"],
- ["El Hachmia Ait Ben", "Haddou"],
- ["Mustapha Alaoui", "Faris"],
- ["Ali", "Benomar"],
- ["Mohamed", "Yahyaoui"]
+ ["Xueyi", "Li"],
+ ["Antonio", "Valencia"],
+ ["Hollis", "McClory"],
+ ["Ellen", "Sapp"],
+ ["Kimberly B", "Kegel"],
+ ["Marian", "Difiglia"]
],
- "publisher": "African health sciences",
- "issn": "1729-0503",
- "date": "2015-12-01",
- "abstract": "Huntington's disease (HD) occurs worldwide with prevalence varying from 0.1 to 10/100,000 depending of the ethnic origin. Since no data is available in the Maghreb population, the aim of this study is to describe clinical and genetic characteristics of Huntington patients of Moroccan origin.",
+ "publisher": "Biochemical and biophysical research communications",
+ "issn": "1090-2104",
+ "date": "2012-04-20",
+ "abstract": "Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. Positron emission tomography studies have revealed a decline in glucose metabolism in the brain of patients with HD by a mechanism that has not been established. We examined glucose utilization in embryonic primary cortical neurons of wild-type (WT) and HD knock-in mice, which have 140 CAG repeats inserted in the endogenous mouse huntingtin gene (HD(140Q/140Q)). Primary HD(140Q/140Q) cortical neurons took up significantly less glucose than did WT neurons. Expression of permanently inactive and permanently active forms of Rab11 correspondingly altered glucose uptake in WT neurons, suggesting that normal activity of Rab11 is needed for neuronal uptake of glucose. It is known that Rab11 activity is diminished in HD(140Q/140Q) neurons. Expression of dominant active Rab11 to enhance the activity of Rab11 normalized glucose uptake in HD(140Q/140Q) neurons. These results suggest that deficient activity of Rab11 is a novel mechanism for glucose hypometabolism in HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26958025"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22542623"
},
{
- "id": "pmid:26900923",
+ "id": "pmid:26307259",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26900923",
- "title": "Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26307259",
+ "title": "Red/ET recombination with chimeric oligonucleotides allows rapid generation of BAC transgenes harboring full-length or truncated huntingtin cDNA.",
"type": "article-journal",
- "doi": "10.1038/nn.4256",
+ "doi": "10.2144/000113908",
"authors": [
- ["Peter", "Langfelder"],
- ["Jeffrey P", "Cantle"],
- ["Doxa", "Chatzopoulou"],
- ["Nan", "Wang"],
- ["Fuying", "Gao"],
- ["Ismael", "Al-Ramahi"],
- ["Xiao-Hong", "Lu"],
- ["Eliana Marisa", "Ramos"],
- ["Karla", "El-Zein"],
- ["Yining", "Zhao"],
- ["Sandeep", "Deverasetty"],
- ["Andreas", "Tebbe"],
- ["Christoph", "Schaab"],
- ["Daniel J", "Lavery"],
- ["David", "Howland"],
- ["Seung", "Kwak"],
- ["Juan", "Botas"],
- ["Jeffrey S", "Aaronson"],
- ["Jim", "Rosinski"],
- ["Giovanni", "Coppola"],
- ["Steve", "Horvath"],
- ["X William", "Yang"]
+ ["Stefanie", "Hager"],
+ ["Saskia", "L\u00f6sch"],
+ ["Stephan", "Noll"],
+ ["Loren", "Khan-Vaughan"],
+ ["Michelle E", "Ehrlich"],
+ ["Harald", "Kranz"]
],
- "publisher": "Nature neuroscience",
- "issn": "1546-1726",
- "date": "2016-02-22",
- "abstract": "To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington's disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat lengths. We found repeat length-dependent transcriptional signatures to be prominent in the striatum, less so in cortex, and minimal in the liver. Coexpression network analyses revealed 13 striatal and 5 cortical modules that correlated highly with CAG length and age, and that were preserved in HD models and sometimes in patients. Top striatal modules implicated mHtt CAG length and age in graded impairment in the expression of identity genes for striatal medium spiny neurons and in dysregulation of cyclic AMP signaling, cell death and protocadherin genes. We used proteomics to confirm 790 genes and 5 striatal modules with CAG length-dependent dysregulation at the protein level, and validated 22 striatal module genes as modifiers of mHtt toxicities in vivo.",
+ "publisher": "BioTechniques",
+ "issn": "1940-9818",
+ "date": "2012-07-01",
+ "abstract": "Huntington's disease (HD) is a fatal neurodegenerative disorder that is caused by a CAG repeat expansion encoding a polyglutamine tract in the huntingtin (htt) gene. None of the existing HD mouse models recapitulate the exact disease symptoms and course as it is seen in humans and the generation of further HD disease models is challenging because of the size and complexity of the htt gene locus. Starting from a single substrate plasmid harboring human htt cDNA comprising 98 glutamine (Q) residues, we applied Red/ET recombination to generate four BDNF-BAC transgenes harboring full-length or truncated (N171) htt cDNA comprising 98 or 15 Q residues. BDNF (brain-derived neurotrophic factor) is expressed in the cortical neurons projecting to the striatal medium spiny neurons, and was used to direct htt transgene expression to investigate the contribution of these cell types to HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26900923"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26307259"
},
{
- "id": "pmid:26849111",
+ "id": "pmid:22454241",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26849111",
- "title": "The HTT CAG-Expansion Mutation Determines Age at Death but Not Disease Duration in Huntington Disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22454241",
+ "title": "Genetic polymorphisms of 5-HTT and DAT but not COMT differentially affect verbal and visuospatial working memory functioning.",
"type": "article-journal",
- "doi": "10.1016/j.ajhg.2015.12.018",
+ "doi": "10.1007/s00406-012-0312-0",
"authors": [
- ["Jae Whan", "Keum"],
- ["Aram", "Shin"],
- ["Tammy", "Gillis"],
- ["Jayalakshmi Srinidhi", "Mysore"],
- ["Kawther", "Abu Elneel"],
- ["Diane", "Lucente"],
- ["Tiffany", "Hadzi"],
- ["Peter", "Holmans"],
- ["Lesley", "Jones"],
- ["Michael", "Orth"],
- ["Seung", "Kwak"],
- ["Marcy E", "MacDonald"],
- ["James F", "Gusella"],
- ["Jong-Min", "Lee"]
+ ["David", "Zilles"],
+ ["Jobst", "Meyer"],
+ ["Thomas", "Schneider-Axmann"],
+ ["Savira", "Ekawardhani"],
+ ["Eva", "Gruber"],
+ ["Peter", "Falkai"],
+ ["Oliver", "Gruber"]
],
- "publisher": "American journal of human genetics",
- "issn": "1537-6605",
- "date": "2016-02-04",
- "abstract": "Huntington disease (HD) is caused by an expanded HTT CAG repeat that leads in a length-dependent, completely dominant manner to onset of a characteristic movement disorder. HD also displays early mortality, so we tested whether the expanded CAG repeat exerts a dominant influence on age at death and on the duration of clinical disease. We found that, as with clinical onset, HD age at death is determined by expanded CAG-repeat length and has no contribution from the normal CAG allele. Surprisingly, disease duration is independent of the mutation's length. It is also unaffected by a strong genetic modifier of HD motor onset. These findings suggest two parsimonious alternatives. (1) HD pathogenesis is driven by mutant huntingtin, but before or near motor onset, sufficient CAG-driven damage occurs to permit CAG-independent processes and then lead to eventual death. In this scenario, some pathological changes and their clinical correlates could still worsen in a CAG-driven manner after disease onset, but these CAG-related progressive changes do not themselves determine duration. Alternatively, (2) HD pathogenesis is driven by mutant huntingtin acting in a CAG-dependent manner with different time courses in multiple cell types, and the cellular targets that lead to motor onset and death are different and independent. In this scenario, processes driven by HTT CAG length lead directly to death but not via the striatal pathology associated with motor manifestations. Each scenario has important ramifications for the design and testing of potential therapeutics, especially those aimed at preventing or delaying characteristic motor manifestations.",
+ "publisher": "European archives of psychiatry and clinical neuroscience",
+ "issn": "1433-8491",
+ "date": "2012-03-28",
+ "abstract": "Working memory deficits are found in different psychiatric populations and are most pronounced in schizophrenia. There is preliminary evidence from pharmacological studies that the verbal and visuospatial subcomponents of working memory are subject to differential neurotransmitter modulation. Here, we investigated the impact of well-known polymorphisms of the dopamine transporter gene (SLC6A3, DAT) and the catechol-O-methyl-transferase gene (COMT) as well as the serotonin transporter gene (SLC6A4, 5-HTT) on these specific working memory subcomponents in a mixed sample of patients and healthy individuals. Twenty healthy subjects and 80 patients diagnosed with schizophrenia, bipolar I disorder, or obsessive-compulsive disorder underwent genotyping for the DAT variable number of tandem repeats (VNTR), the COMT val/met-, and the 5-HTT promoter length polymorphism (5-HTTLPR) and neuropsychological testing using a battery of well-characterized, brain circuit-specific working memory tasks. DAT genotype revealed a significant and selective effect on visuospatial working memory, while there was no effect on verbal working memory functioning. 5-HTT genotype, by contrast, exerted a significant and selective effect on verbal working memory task performance. COMT genotype did not show any influence on either working memory domain. The results of the present study provide evidence for a differential impact of genetic polymorphisms of the dopaminergic and serotonergic systems on verbal and visuospatial working memory functioning. Together with prior evidence suggesting the existence of subgroups of schizophrenia patients exhibiting isolated deficits in only one working memory domain, this finding further supports the idea of endophenotypically and pathophysiologically distinct subgroups of schizophrenia with implications for personalized therapeutic approaches.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26849111"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22454241"
},
{
- "id": "pmid:26846325",
+ "id": "pmid:22425717",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26846325",
- "title": "Reduced Mitochondrial Function in Human Huntington Disease Lymphoblasts is Not Due to Alterations in Cardiolipin Metabolism or Mitochondrial Supercomplex Assembly.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22425717",
+ "title": "Impaired cortico-striatal functional connectivity in prodromal Huntington's Disease.",
"type": "article-journal",
- "doi": "10.1007/s11745-015-4110-0",
+ "doi": "10.1016/j.neulet.2012.02.095",
"authors": [
- ["Edgard M", "Mejia"],
- ["Sarah", "Chau"],
- ["Genevieve C", "Sparagna"],
- ["Simonetta", "Sipione"],
- ["Grant M", "Hatch"]
+ ["Paul G", "Unschuld"],
+ ["Suresh E", "Joel"],
+ ["Xinyang", "Liu"],
+ ["Megan", "Shanahan"],
+ ["Russell L", "Margolis"],
+ ["Kevin M", "Biglan"],
+ ["Susan S", "Bassett"],
+ ["David J", "Schretlen"],
+ ["Graham W", "Redgrave"],
+ ["Peter C M", "van Zijl"],
+ ["James J", "Pekar"],
+ ["Christopher A", "Ross"]
],
- "publisher": "Lipids",
- "issn": "1558-9307",
- "date": "2016-02-04",
- "abstract": "Huntington's Disease (HD) is an autosomal dominant disease that occurs as a result of expansion of the trinucleotide repeat CAG (glutamine) on the HTT gene. HD patients exhibit various forms of mitochondrial dysfunction within neurons and peripheral tissues. Cardiolipin (Ptd2Gro) is a polyglycerophospholipid found exclusively in mitochondria and is important for maintaining mitochondrial function. We examined if altered Ptd2Gro metabolism was involved in the mitochondrial dysfunction associated with HD. Mitochondrial basal respiration, spare respiratory capacity, ATP coupling efficiency and rate of glycolysis were markedly diminished in Epstein-Barr virus transformed HD lymphoblasts compared to controls (CTRL). Mitochondrial supercomplex formation and Complex I activity within these supercomplexes did not vary between HD patients with different length of CAG repeats and appeared unaltered compared to CTRL. In contrast, in vitro Complex I enzyme activity in mitochondrial enriched samples was reduced in HD lymphoblasts compared to CTRL. The total cellular pool size of Ptd2Gro and its synthesis/remodeling from [(3)H]acetate/[(14)C]oleate were unaltered in HD lymphoblasts compared to CTRL. In addition, the molecular species of Ptd2Gro were essentially unaltered in HD lymphoblasts compared to CTRL. We conclude that compared to CTRL lymphoblasts, HD lymphoblasts display impaired mitochondrial basal respiration, spare respiratory capacity, ATP coupling efficiency and rate of glycolysis with any pathological CAG repeat length, but this is not due to alterations in Ptd2Gro metabolism. We suggest that HD patient lymphoblasts may be a useful model to study defective energy metabolism that does not involve alterations in Ptd2Gro metabolism.",
+ "publisher": "Neuroscience letters",
+ "issn": "1872-7972",
+ "date": "2012-03-07",
+ "abstract": "Huntington's Disease (HD) is a neurodegenerative disease caused by a CAG triplet-repeat expansion-mutation in the Huntingtin gene. Subjects at risk for HD can be identified by genetic testing in the prodromal phase. Structural changes of basal-ganglia nuclei such as the caudate nucleus are well-replicated findings observable early in prodromal-HD subjects and may be preceded by distinct functional alterations of cortico-striatal circuits. This study aims to assess functional integrity of the motor system as a cortico-striatal circuit with particular clinical relevance in HD. Ten subjects in the prodromal phase of HD and ten matched controls were administered blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) at rest (3T). Functional connectivity was measured as synchrony of BOLD activity between the caudate nucleus and thirteen cortical brain regions (seeds). Basal-ganglia volumes were assessed as established markers of disease progression in prodromal-HD. Linear regression analysis was performed to test for a relationship between structural changes and group differences in functional connectivity. Prodromal-HD subjects showed reduced BOLD synchrony between two seeds in the premotor cortex (BA6) and the caudate nucleus. While similar effect sizes could be observed for reduced basal-ganglia volumes and differences in functional connectivity, coefficients of determination indicate a moderate relationship between functional connectivity and striatal atrophy. Our data show reduced cortico-striatal functional connectivity at rest in prodromal-HD and suggest a relation to early structural brain changes. Additional longitudinal studies are necessary to elucidate the temporal relationship between functional alterations and earliest structural brain changes in prodromal-HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26846325"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22425717"
},
{
- "id": "pmid:26682993",
+ "id": "pmid:22383888",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26682993",
- "title": "Determinants of Onset of Huntington's Disease with Behavioral Symptoms: Insight from 92 Patients.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22383888",
+ "title": "A pathogenic mechanism in Huntington's disease involves small CAG-repeated RNAs with neurotoxic activity.",
"type": "article-journal",
- "doi": "10.3233/jhd-150166",
+ "doi": "10.1371/journal.pgen.1002481",
"authors": [
- ["Abhishek", "Lenka"],
- ["Nitish L", "Kamble"],
- ["V", "Sowmya"],
- ["Ketan", "Jhunjhunwala"],
- ["Ravi", "Yadav"],
- ["M", "Netravathi"],
- ["Mahesh", "Kandasamy"],
- ["Nagaraj S", "Moily"],
- ["Meera", "Purushottam"],
- ["Sanjeev", "Jain"],
- ["Pramod Kumar", "Pal"]
+ ["M\u00f3nica", "Ba\u00f1ez-Coronel"],
+ ["Silvia", "Porta"],
+ ["Birgit", "Kagerbauer"],
+ ["Elisabet", "Mateu-Huertas"],
+ ["Lorena", "Pantano"],
+ ["Isidre", "Ferrer"],
+ ["Manuel", "Guzm\u00e1n"],
+ ["Xavier", "Estivill"],
+ ["Eul\u00e0lia", "Mart\u00ed"]
],
- "publisher": "Journal of Huntington's disease",
- "issn": "1879-6400",
- "date": "2015-01-01",
- "abstract": "Huntington's disease (HD) is a genetically mediated neurodegenerative disorder characterized by presence of involuntary movements, behavioral problems and cognitive dysfunctions. Though few patients with HD may have behavioral symptoms at onset of the disease, studies comparing patients with behavioral symptoms at the onset of HD with those having motor symptoms are sparse.",
+ "publisher": "PLoS genetics",
+ "issn": "1553-7404",
+ "date": "2012-02-23",
+ "abstract": "Huntington's disease (HD) is an autosomal dominantly inherited disorder caused by the expansion of CAG repeats in the Huntingtin (HTT) gene. The abnormally extended polyglutamine in the HTT protein encoded by the CAG repeats has toxic effects. Here, we provide evidence to support that the mutant HTT CAG repeats interfere with cell viability at the RNA level. In human neuronal cells, expanded HTT exon-1 mRNA with CAG repeat lengths above the threshold for complete penetrance (40 or greater) induced cell death and increased levels of small CAG-repeated RNAs (sCAGs), of \u224821 nucleotides in a Dicer-dependent manner. The severity of the toxic effect of HTT mRNA and sCAG generation correlated with CAG expansion length. Small RNAs obtained from cells expressing mutant HTT and from HD human brains significantly decreased neuronal viability, in an Ago2-dependent mechanism. In both cases, the use of anti-miRs specific for sCAGs efficiently blocked the toxic effect, supporting a key role of sCAGs in HTT-mediated toxicity. Luciferase-reporter assays showed that expanded HTT silences the expression of CTG-containing genes that are down-regulated in HD. These results suggest a possible link between HD and sCAG expression with an aberrant activation of the siRNA/miRNA gene silencing machinery, which may trigger a detrimental response. The identification of the specific cellular processes affected by sCAGs may provide insights into the pathogenic mechanisms underlying HD, offering opportunities to develop new therapeutic approaches.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26682993"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22383888"
},
{
- "id": "pmid:26621114",
+ "id": "pmid:22367996",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26621114",
- "title": "Differential changes in thalamic and cortical excitatory synapses onto striatal spiny projection neurons in a Huntington disease mouse model.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22367996",
+ "title": "Loss of junctophilin-3 contributes to Huntington disease-like 2 pathogenesis.",
"type": "article-journal",
- "doi": "10.1016/j.nbd.2015.11.020",
+ "doi": "10.1002/ana.22598",
"authors": [
- ["Karolina", "Kolodziejczyk"],
- ["Lynn A", "Raymond"]
+ ["Ana I", "Seixas"],
+ ["Susan E", "Holmes"],
+ ["Hiroshi", "Takeshima"],
+ ["Amira", "Pavlovich"],
+ ["Nancy", "Sachs"],
+ ["Jennifer L", "Pruitt"],
+ ["Isabel", "Silveira"],
+ ["Christopher A", "Ross"],
+ ["Russell L", "Margolis"],
+ ["Dobrila D", "Rudnicki"]
],
- "publisher": "Neurobiology of disease",
- "issn": "1095-953X",
- "date": "2015-11-24",
- "abstract": "Huntington disease (HD), a neurodegenerative disorder caused by CAG repeat expansion in the gene encoding huntingtin, predominantly affects the striatum, especially the spiny projection neurons (SPN). The striatum receives excitatory input from cortex and thalamus, and the role of the former has been well-studied in HD. Here, we report that mutated huntingtin alters function of thalamostriatal connections. We used a novel thalamostriatal (T-S) coculture and an established corticostriatal (C-S) coculture, generated from YAC128 HD and WT (FVB/NJ background strain) mice, to investigate excitatory neurotransmission onto striatal SPN. SPN in T-S coculture from WT mice showed similar mini-excitatory postsynaptic current (mEPSC) frequency and amplitude as in C-S coculture; however, both the frequency and amplitude were significantly reduced in YAC128 T-S coculture. Further investigation in T-S coculture showed similar excitatory synapse density in WT and YAC128 SPN dendrites by immunostaining, suggesting changes in total dendritic length or probability of release as possible explanations for mEPSC frequency changes. Synaptic N-methyl-D-aspartate receptor (NMDAR) current was similar, but extrasynaptic current, associated with cell death signaling, was enhanced in YAC128 SPN in T-S coculture. Employing optical stimulation of cortical versus thalamic afferents and recording from striatal SPN in brain slice, we found increased glutamate release probability and reduced AMPAR/NMDAR current ratios in thalamostriatal synapses, most prominently in YAC128. Enhanced extrasynaptic NMDAR current in YAC128 SPN was apparent with both cortical and thalamic stimulation. We conclude that thalamic afferents to the striatum are affected early, prior to an overt HD phenotype; however, changes in NMDAR localization in SPN are independent of the source of glutamatergic input.",
+ "publisher": "Annals of neurology",
+ "issn": "1531-8249",
+ "date": "2012-02-01",
+ "abstract": "Huntington disease-like 2 (HDL2) is a progressive, late onset autosomal dominant neurodegenerative disorder, with remarkable similarities to Huntington disease (HD). HDL2 is caused by a CTG/CAG repeat expansion. In the CTG orientation, the repeat is located within the alternatively spliced exon 2A of junctophilin-3 (JPH3), potentially encoding polyleucine and polyalanine, whereas on the strand antisense to JPH3, the repeat is in frame to encode polyglutamine. The JPH3 protein product serves to stabilize junctional membrane complexes and regulate neuronal calcium flux. We have previously demonstrated the potential pathogenic properties of JPH3 transcripts containing expanded CUG repeats. The aim of this study was to test the possibility that loss of JPH3 expression or expanded amino acid tracts also contribute to HDL2 pathogenesis.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26621114"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22367996"
},
{
- "id": "pmid:26557176",
+ "id": "pmid:22359536",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26557176",
- "title": "Childhood-onset (Juvenile) Huntington's disease: A rare case report.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22359536",
+ "title": "Characterization of a large group of individuals with huntington disease and their relatives enrolled in the COHORT study.",
"type": "article-journal",
- "doi": "10.4103/1817-1745.165709",
+ "doi": "10.1371/journal.pone.0029522",
"authors": [
- ["Kailash Chandra", "Patra"],
- ["Mukund Sudhir", "Shirolkar"]
+ ["E Ray", "Dorsey"]
],
- "publisher": "Journal of pediatric neurosciences",
- "issn": "1817-1745",
- "date": "2015-01-01",
- "abstract": "Huntington's disease (HD) is a rare dominantly inherited neurodegenerative disorder characterized clinically by a combination of abnormal involuntary (choreic) movements, neuropsychiatric manifestations, and dementia. It is caused by an unstable CAG repeat expansion in the gene IT15 which encodes a Huntingtin protein. We present a case of a 9 year old boy who had developmental regression starting from the age of 8 years of age along with resistant seizures and signs of cerebellar involvement with absence of chorea and is on anticonvulsants, baclofen, and tetrabenzine. As is expected in a case of childhood-onset HD, our patient is rapidly deteriorating and is currently in the terminal phase of his illness along with resistant convulsions.",
+ "publisher": "PloS one",
+ "issn": "1932-6203",
+ "date": "2012-02-16",
+ "abstract": "Careful characterization of the phenotype and genotype of Huntington disease (HD) can foster better understanding of the condition.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26557176"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22359536"
},
{
- "id": "pmid:26439718",
+ "id": "pmid:22237433",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26439718",
- "title": "Huntington Disease: Molecular Diagnostics Approach.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22237433",
+ "title": "Assessing the analytic validity of molecular testing for Huntington disease using data from an external proficiency testing survey.",
"type": "article-journal",
- "doi": "10.1002/0471142905.hg0926s87",
+ "doi": "10.1038/gim.0b013e3182310bb5",
"authors": [
- ["Murat", "Bastepe"],
- ["Winnie", "Xin"]
+ ["Glenn E", "Palomaki"],
+ ["C Sue", "Richards"]
],
- "publisher": "Current protocols in human genetics",
- "issn": "1934-8258",
- "date": "2015-10-06",
- "abstract": "Huntington disease (HD) is caused by expansion of a CAG trinucleotide repeat in the first exon of the Huntingtin (HTT) gene. Molecular testing of Huntington disease for diagnostic confirmation and disease prediction requires detection of the CAG repeat expansion. There are three main types of HD genetic testing: (1) diagnostic testing to confirm or rule out disease, (2) presymptomatic testing to determine whether an at-risk individual inherited the expanded allele, and (3) prenatal testing to determine whether the fetus has inherited the expanded allele. This unit includes protocols that describe the complementary use of polymerase chain reactions (PCR) and Southern blot hybridization to accurately measure the CAG trinucleotide repeat size and interpret the test results. In addition, an indirect linkage analysis that does not reveal the unwanted parental HD status in a prenatal testing will also be discussed.",
+ "publisher": "Genetics in medicine : official journal of the American College of Medical Genetics",
+ "issn": "1530-0366",
+ "date": "2011-09-26",
+ "abstract": "Documenting high analytic validity of the molecular diagnostic test for Huntington disease is important because of counseling implications. This dominantly inherited adult onset disorder (prevalence of three or more per 100,000) is characterized by chorea, ataxia, and personality changes. The molecular basis is excessive CAG repeats in the HTT gene.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26439718"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22237433"
},
{
- "id": "pmid:26397897",
+ "id": "pmid:22235343",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26397897",
- "title": "Huntingtin Exists as Multiple Splice Forms in Human Brain.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22235343",
+ "title": "Variation within the Huntington's disease gene influences normal brain structure.",
"type": "article-journal",
- "doi": "10.3233/jhd-150151",
+ "doi": "10.1371/journal.pone.0029809",
"authors": [
- ["Matthew", "Mort"],
- ["Francesca A", "Carlisle"],
- ["Adrian J", "Waite"],
- ["Lyn", "Elliston"],
- ["Nicholas D", "Allen"],
- ["Lesley", "Jones"],
- ["Alis C", "Hughes"]
+ ["Mark", "M\u00fchlau"],
+ ["Juliane", "Winkelmann"],
+ ["Dan", "Rujescu"],
+ ["Ina", "Giegling"],
+ ["Nikolaos", "Koutsouleris"],
+ ["Christian", "Gaser"],
+ ["Milan", "Arsic"],
+ ["Adolph", "Weindl"],
+ ["Maximilian", "Reiser"],
+ ["Eva M", "Meisenzahl"]
],
- "publisher": "Journal of Huntington's disease",
- "issn": "1879-6400",
- "date": "2015-01-01",
- "abstract": "A CAG repeat expansion in HTT has been known to cause Huntington's disease for over 20 years. The genomic sequence of the 67 exon HTT is clear but few reports have detailed alternative splicing or alternative transcripts. Most eukaryotic genes with multiple exons show alternative splicing that increases the diversity of the transcriptome and proteome: it would be surprising if a gene with 67 known exons in its two major transcripts did not present some alternative transcripts.",
+ "publisher": "PloS one",
+ "issn": "1932-6203",
+ "date": "2012-01-03",
+ "abstract": "Genetics of the variability of normal and diseased brain structure largely remains to be elucidated. Expansions of certain trinucleotide repeats cause neurodegenerative disorders of which Huntington's disease constitutes the most common example. Here, we test the hypothesis that variation within the IT15 gene on chromosome 4, whose expansion causes Huntington's disease, influences normal human brain structure. In 278 normal subjects, we determined CAG repeat length within the IT15 gene on chromosome 4 and analyzed high-resolution T1-weighted magnetic resonance images by the use of voxel-based morphometry. We found an increase of GM with increasing long CAG repeat and its interaction with age within the pallidum, which is involved in Huntington's disease. Our study demonstrates that a certain trinucleotide repeat influences normal brain structure in humans. This result may have important implications for the understanding of both the healthy and diseased brain.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26397897"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22235343"
},
{
- "id": "pmid:26397895",
+ "id": "pmid:22219281",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26397895",
- "title": "Is There Convincing Evidence that Intermediate Repeats in the HTT Gene Cause Huntington's Disease?",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22219281",
+ "title": "Transgenic mouse model expressing the caspase 6 fragment of mutant huntingtin.",
"type": "article-journal",
- "doi": "10.3233/jhd-140120",
+ "doi": "10.1523/jneurosci.1305-11.2012",
"authors": [
- ["Mayke", "Oosterloo"],
- ["Martine J", "Van Belzen"],
- ["Emilia K", "Bijlsma"],
- ["Raymund A C", "Roos"]
+ ["Elaine", "Waldron-Roby"],
+ ["Tamara", "Ratovitski"],
+ ["XiaoFang", "Wang"],
+ ["Mali", "Jiang"],
+ ["Erin", "Watkin"],
+ ["Nikolas", "Arbez"],
+ ["Rona K", "Graham"],
+ ["Michael R", "Hayden"],
+ ["Zhipeng", "Hou"],
+ ["Susumu", "Mori"],
+ ["Deborah", "Swing"],
+ ["Mikhail", "Pletnikov"],
+ ["Wenzhen", "Duan"],
+ ["Lino", "Tessarollo"],
+ ["Christopher A", "Ross"]
],
- "publisher": "Journal of Huntington's disease",
- "issn": "1879-6400",
- "date": "2015-01-01",
- "abstract": "Huntington's disease (HD) is a neurodegenerative disease associated with a CAG repeat expansion in the Huntingtin (HTT) gene. A trinucleotide size between 27 and 35 is considered 'intermediate' and not to cause symptoms and signs of HD. There are articles claiming otherwise, however publishing only the cases that have a HD phenotype introduces a significant publication bias. Our objective is to determine if there is convincing evidence that intermediate repeats (IA) cause HD.",
+ "publisher": "The Journal of neuroscience : the official journal of the Society for Neuroscience",
+ "issn": "1529-2401",
+ "date": "2012-01-04",
+ "abstract": "Huntington's disease (HD) is caused by a polyglutamine expansion in the Huntingtin (Htt) protein. Proteolytic cleavage of Htt into toxic N-terminal fragments is believed to be a key aspect of pathogenesis. The best characterized putative cleavage event is at amino acid 586, hypothesized to be mediated by caspase 6. A corollary of the caspase 6 cleavage hypothesis is that the caspase 6 fragment should be a toxic fragment. To test this hypothesis, and further characterize the role of this fragment, we have generated transgenic mice expressing the N-terminal 586 aa of Htt with a polyglutamine repeat length of 82 (N586-82Q), under the control of the prion promoter. N586-82Q mice show a clear progressive rotarod deficit by 4 months of age, and are hyperactive starting at 5 months, later changing to hypoactivity before early mortality. MRI studies reveal widespread brain atrophy, and histologic studies demonstrate an abundance of Htt aggregates, mostly cytoplasmic, which are predominantly composed of the N586-82Q polypeptide. Smaller soluble N-terminal fragments appear to accumulate over time, peaking at 4 months, and are predominantly found in the nuclear fraction. This model appears to have a phenotype more severe than current full-length Htt models, but less severe than HD mouse models expressing shorter Htt fragments. These studies suggest that the caspase 6 fragment may be a transient intermediate, that fragment size is a factor contributing to the rate of disease progression, and that short soluble nuclear fragments may be most relevant to pathogenesis.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26397895"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22219281"
},
{
- "id": "pmid:26375764",
+ "id": "pmid:23925262",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26375764",
- "title": "Oncologic Phenotype of Peripheral Neuroblastic Tumors Associated With PHOX2B Non-Polyalanine Repeat Expansion Mutations.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23925262",
+ "title": "A mixed fixed ratio/progressive ratio procedure reveals an apathy phenotype in the BAC HD and the z_Q175 KI mouse models of Huntington's disease.",
"type": "article-journal",
- "doi": "10.1002/pbc.25723",
+ "doi": "10.1371/4f972cffe82c0",
"authors": [
- ["Solveig", "Heide"],
- ["Julien", "Masliah-Planchon"],
- ["Bertrand", "Isidor"],
- ["Anne", "Guimier"],
- ["Damien", "Bodet"],
- ["Carole", "Coze"],
- ["Anne", "Deville"],
- ["Estelle", "Thebault"],
- ["Corinne Jeanne", "Pasquier"],
- ["Elisabeth", "Cassagnau"],
- ["Gaelle", "Pierron"],
- ["Nathalie", "Cl\u00e9ment"],
- ["Gudrun", "Schleiermacher"],
- ["Jeanne", "Amiel"],
- ["Olivier", "Delattre"],
- ["Michel", "Peuchmaur"],
- ["Franck", "Bourdeaut"]
+ ["Stephen", "Oakeshott"],
+ ["Russell", "Port"],
+ ["Jane", "Cummins-Sutphen"],
+ ["Jason", "Berger"],
+ ["Judy", "Watson-Johnson"],
+ ["Sylvie", "Ramboz"],
+ ["Neil", "Paterson"],
+ ["Seung", "Kwak"],
+ ["David", "Howland"],
+ ["Dani", "Brunner"]
],
- "publisher": "Pediatric blood & cancer",
- "issn": "1545-5017",
- "date": "2015-09-16",
- "abstract": "Germline non-polyalanine repeat expansion mutations in PHOX2B (PHOX2B NPARM) predispose to peripheral neuroblastic tumors (PNT), frequently in association with other neurocristopathies: Hirschsprung disease (HSCR) or congenital central hypoventilation syndrome (CCHS). Although PHOX2B polyalanine repeat expansions predispose to a low incidence of benign PNTs, the oncologic phenotype associated with PHOX2B NPARM is still not known in detail.",
+ "publisher": "PLoS currents",
+ "issn": "2157-3999",
+ "date": "2012-04-25",
+ "abstract": "Apathy, characterized by generally reduced interest in and likelihood to perform goal-directed actions, is a recognized symptom of Huntington's disease (HD), a devastating neurological disorder caused by a CAG repeat expansion of the Htt gene located on chromosome 4. The present experiments used a modified progressive ratio task that incorporated a fixed-ratio schedule of reinforcement component to assess consummatory behavior, and a progressive-ratio schedule component that required increasing numbers of lever-presses for successive reinforcers (0.01 ml of evaporated milk). The studies revealed an apathetic phenotype in two mouse models of HD, with decreased response rates either overall or only at higher ratio requirements in the progressive-ratio component relative to wild-type controls. Based on the procedure used (within-session fixed- and progressive-ratio components), it is proposed that an observed phenotype can be ascribed either specifically to reduced motivation to work for food reinforcement or more generally to deficits in consummatory behavior. This procedure provides a simple means to assess this type of phenotype in rodents, with issues in consummatory vs. incentive motivation reflected in general alterations in fixed- versus progressive alterations on an escalating-ratio schedules respectively, providing translational measures of the amotivation/apathy construct of the human realm to the homologous construct of incentive motivation in preclinical models of human disease.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26375764"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23925262"
},
{
- "id": "pmid:26247199",
+ "id": "pmid:23476655",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26247199",
- "title": "Suppression of Somatic Expansion Delays the Onset of Pathophysiology in a Mouse Model of Huntington's Disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23476655",
+ "title": "Predicting Disease Onset from Mutation Status Using Proband and Relative Data with Applications to Huntington's Disease.",
"type": "article-journal",
- "doi": "10.1371/journal.pgen.1005267",
+ "doi": "10.1155/2012/375935",
"authors": [
- ["Helen", "Budworth"],
- ["Faye R", "Harris"],
- ["Paul", "Williams"],
- ["Do Yup", "Lee"],
- ["Amy", "Holt"],
- ["Jens", "Pahnke"],
- ["Bartosz", "Szczesny"],
- ["Karina", "Acevedo-Torres"],
- ["Sylvette", "Ayala-Pe\u00f1a"],
- ["Cynthia T", "McMurray"]
+ ["Tianle", "Chen"],
+ ["Yuanjia", "Wang"],
+ ["Yanyuan", "Ma"],
+ ["Karen", "Marder"],
+ ["Douglas R", "Langbehn"]
],
- "publisher": "PLoS genetics",
- "issn": "1553-7404",
- "date": "2015-08-06",
- "abstract": "Huntington's Disease (HD) is caused by inheritance of a single disease-length allele harboring an expanded CAG repeat, which continues to expand in somatic tissues with age. The inherited disease allele expresses a toxic protein, and whether further somatic expansion adds to toxicity is unknown. We have created an HD mouse model that resolves the effects of the inherited and somatic expansions. We show here that suppressing somatic expansion substantially delays the onset of disease in littermates that inherit the same disease-length allele. Furthermore, a pharmacological inhibitor, XJB-5-131, inhibits the lengthening of the repeat tracks, and correlates with rescue of motor decline in these animals. The results provide evidence that pharmacological approaches to offset disease progression are possible.",
+ "publisher": "Journal of probability and statistics",
+ "issn": "1687-952X",
+ "date": "2012-01-01",
+ "abstract": "Huntington's disease (HD) is a progressive neurodegenerative disorder caused by an expansion of CAG repeats in the IT15 gene. The age-at-onset (AAO) of HD is inversely related to the CAG repeat length and the minimum length thought to cause HD is 36. Accurate estimation of the AAO distribution based on CAG repeat length is important for genetic counseling and the design of clinical trials. In the Cooperative Huntington's Observational Research Trial (COHORT) study, the CAG repeat length is known for the proband participants. However, whether a family member shares the huntingtin gene status (CAG expanded or not) with the proband is unknown. In this work, we use the expectation-maximization (EM) algorithm to handle the missing huntingtin gene information in first-degree family members in COHORT, assuming that a family member has the same CAG length as the proband if the family member carries a huntingtin gene mutation. We perform simulation studies to examine performance of the proposed method and apply the methods to analyze COHORT proband and family combined data. Our analyses reveal that the estimated cumulative risk of HD symptom onset obtained from the combined data is slightly lower than the risk estimated from the proband data alone.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26247199"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23476655"
},
{
- "id": "pmid:26232222",
+ "id": "pmid:22179316",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26232222",
- "title": "Identification of Genetic Factors that Modify Clinical Onset of Huntington's Disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22179316",
+ "title": "Sirt1 mediates neuroprotection from mutant huntingtin by activation of the TORC1 and CREB transcriptional pathway.",
"type": "article-journal",
- "doi": "10.1016/j.cell.2015.07.003",
- "authors": [],
- "publisher": "Cell",
- "issn": "1097-4172",
- "date": "2015-07-30",
- "abstract": "As a Mendelian neurodegenerative disorder, the genetic risk of Huntington's disease (HD) is conferred entirely by an HTT CAG repeat expansion whose length is the primary determinant of the rate of pathogenesis leading to disease onset. To investigate the pathogenic process that precedes disease, we used genome-wide association (GWA) analysis to identify loci harboring genetic variations that alter the age at neurological onset of HD. A chromosome 15 locus displays two independent effects that accelerate or delay onset by 6.1 years and 1.4 years, respectively, whereas a chromosome 8 locus hastens onset by 1.6 years. Association at MLH1 and pathway analysis of the full GWA results support a role for DNA handling and repair mechanisms in altering the course of HD. Our findings demonstrate that HD disease modification in humans occurs in nature and offer a genetic route to identifying in-human validated therapeutic targets in this and other Mendelian disorders.",
+ "doi": "10.1038/nm.2559",
+ "authors": [
+ ["Hyunkyung", "Jeong"],
+ ["Dena E", "Cohen"],
+ ["Libin", "Cui"],
+ ["Andrea", "Supinski"],
+ ["Jeffrey N", "Savas"],
+ ["Joseph R", "Mazzulli"],
+ ["John R", "Yates"],
+ ["Laura", "Bordone"],
+ ["Leonard", "Guarente"],
+ ["Dimitri", "Krainc"]
+ ],
+ "publisher": "Nature medicine",
+ "issn": "1546-170X",
+ "date": "2011-12-18",
+ "abstract": "Sirt1, a NAD-dependent protein deacetylase, has emerged as a key regulator of mammalian transcription in response to cellular metabolic status and stress. Here we show that Sirt1 has a neuroprotective role in models of Huntington's disease, an inherited neurodegenerative disorder caused by a glutamine repeat expansion in huntingtin protein (HTT). Brain-specific knockout of Sirt1 results in exacerbation of brain pathology in a mouse model of Huntington's disease, whereas overexpression of Sirt1 improves survival, neuropathology and the expression of brain-derived neurotrophic factor (BDNF) in Huntington's disease mice. We show that Sirt1 deacetylase activity directly targets neurons to mediate neuroprotection from mutant HTT. The neuroprotective effect of Sirt1 requires the presence of CREB-regulated transcription coactivator 1 (TORC1), a brain-specific modulator of CREB activity. We show that under normal conditions, Sirt1 deacetylates and activates TORC1 by promoting its dephosphorylation and its interaction with CREB. We identified BDNF as a key target of Sirt1 and TORC1 transcriptional activity in both normal and Huntington's disease neurons. Mutant HTT interferes with the TORC1-CREB interaction to repress BDNF transcription, and Sirt1 rescues this defect in vitro and in vivo. These studies suggest a key role for Sirt1 in transcriptional networks in both the normal and Huntington's disease brain and offer an opportunity for therapeutic development.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26232222"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22179316"
},
{
- "id": "pmid:26218986",
+ "id": "pmid:22011578",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26218986",
- "title": "Nuclear retention of full-length HTT RNA is mediated by splicing factors MBNL1 and U2AF65.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22011578",
+ "title": "Ser46 phosphorylation and prolyl-isomerase Pin1-mediated isomerization of p53 are key events in p53-dependent apoptosis induced by mutant huntingtin.",
"type": "article-journal",
- "doi": "10.1038/srep12521",
+ "doi": "10.1073/pnas.1106198108",
"authors": [
- ["Xin", "Sun"],
- ["Pan P", "Li"],
- ["Shanshan", "Zhu"],
- ["Rachael", "Cohen"],
- ["Leonard O", "Marque"],
- ["Christopher A", "Ross"],
- ["Stefan M", "Pulst"],
- ["Ho Yin Edwin", "Chan"],
- ["Russell L", "Margolis"],
- ["Dobrila D", "Rudnicki"]
+ ["Alice", "Grison"],
+ ["Fiamma", "Mantovani"],
+ ["Anna", "Comel"],
+ ["Elena", "Agostoni"],
+ ["Stefano", "Gustincich"],
+ ["Francesca", "Persichetti"],
+ ["Giannino", "Del Sal"]
],
- "publisher": "Scientific reports",
- "issn": "2045-2322",
- "date": "2015-07-28",
- "abstract": "Huntington's disease (HD) is caused by a CAG repeat expansion in the huntingtin (HTT) gene. Recent evidence suggests that HD is a consequence of multimodal, non-mutually exclusive mechanisms of pathogenesis that involve both HTT protein- and HTT RNA-triggered mechanisms. Here we provide further evidence for the role of expanded HTT (expHTT) RNA in HD by demonstrating that a fragment of expHTT is cytotoxic in the absence of any translation and that the extent of cytotoxicity is similar to the cytotoxicity of an expHTT protein fragment encoded by a transcript of similar length and with a similar repeat size. In addition, full-length (FL) expHTT is retained in the nucleus. Overexpression of the splicing factor muscleblind-like 1 (MBNL1) increases nuclear retention of expHTT and decreases the expression of expHTT protein in the cytosol. The splicing and nuclear export factor U2AF65 has the opposite effect, decreasing expHTT nuclear retention and increasing expression of expHTT protein. This suggests that MBNL1 and U2AF65 play a role in nuclear export of expHTT RNA.",
+ "publisher": "Proceedings of the National Academy of Sciences of the United States of America",
+ "issn": "1091-6490",
+ "date": "2011-10-19",
+ "abstract": "Huntington disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in the gene coding for huntingtin protein. Several mechanisms have been proposed by which mutant huntingtin (mHtt) may trigger striatal neurodegeneration, including mitochondrial dysfunction, oxidative stress, and apoptosis. Furthermore, mHtt induces DNA damage and activates a stress response. In this context, p53 plays a crucial role in mediating mHtt toxic effects. Here we have dissected the pathway of p53 activation by mHtt in human neuronal cells and in HD mice, with the aim of highlighting critical nodes that may be pharmacologically manipulated for therapeutic intervention. We demonstrate that expression of mHtt causes increased phosphorylation of p53 on Ser46, leading to its interaction with phosphorylation-dependent prolyl isomerase Pin1 and consequent dissociation from the apoptosis inhibitor iASPP, thereby inducing the expression of apoptotic target genes. Inhibition of Ser46 phosphorylation by targeting homeodomain-interacting protein kinase 2 (HIPK2), PKC\u03b4, or ataxia telangiectasia mutated kinase, as well as inhibition of the prolyl isomerase Pin1, prevents mHtt-dependent apoptosis of neuronal cells. These results provide a rationale for the use of small-molecule inhibitors of stress-responsive protein kinases and Pin1 as a potential therapeutic strategy for HD treatment.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26218986"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22011578"
},
{
- "id": "pmid:26148071",
+ "id": "pmid:21989477",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26148071",
- "title": "Exploring Genetic Factors Involved in Huntington Disease Age of Onset: E2F2 as a New Potential Modifier Gene.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21989477",
+ "title": "NMDA receptor gene variations as modifiers in Huntington disease: a replication study.",
"type": "article-journal",
- "doi": "10.1371/journal.pone.0131573",
+ "doi": "10.1371/currents.rrn1247",
"authors": [
- ["Leire", "Valc\u00e1rcel-Ocete"],
- ["Gorka", "Alkorta-Aranburu"],
- ["Mikel", "Iriondo"],
- ["Asier", "Fullaondo"],
- ["Mar\u00eda", "Garc\u00eda-Barcina"],
- ["Jos\u00e9 Manuel", "Fern\u00e1ndez-Garc\u00eda"],
- ["Elena", "Lezcano-Garc\u00eda"],
- ["Jos\u00e9 Mar\u00eda", "Losada-Domingo"],
- ["Javier", "Ruiz-Ojeda"],
- ["Amaia", "\u00c1lvarez de Arcaya"],
- ["Jos\u00e9 Mar\u00eda", "P\u00e9rez-Ramos"],
- ["Raymund A C", "Roos"],
- ["J\u00f8rgen E", "Nielsen"],
["Carsten", "Saft"],
- ["Ana M", "Zubiaga"],
- ["Ana", "Aguirre"]
+ ["J\u00f6rg T", "Epplen"],
+ ["Stefan", "Wieczorek"],
+ ["G Bernhard", "Landwehrmeyer"],
+ ["Raymund A C", "Roos"],
+ ["Justo Garcia", "de Yebenes"],
+ ["Matthias", "Dose"],
+ ["Sarah J", "Tabrizi"],
+ ["David", "Craufurd"],
+ ["Larissa", "Arning"]
],
- "publisher": "PloS one",
- "issn": "1932-6203",
- "date": "2015-07-06",
- "abstract": "Age of onset (AO) of Huntington disease (HD) is mainly determined by the length of the CAG repeat expansion (CAGexp) in exon 1 of the HTT gene. Additional genetic variation has been suggested to contribute to AO, although the mechanism by which it could affect AO is presently unknown. The aim of this study is to explore the contribution of candidate genetic factors to HD AO in order to gain insight into the pathogenic mechanisms underlying this disorder. For that purpose, two AO definitions were used: the earliest age with unequivocal signs of HD (earliest AO or eAO), and the first motor symptoms age (motor AO or mAO). Multiple linear regression analyses were performed between genetic variation within 20 candidate genes and eAO or mAO, using DNA and clinical information of 253 HD patients from REGISTRY project. Gene expression analyses were carried out by RT-qPCR with an independent sample of 35 HD patients from Basque Country Hospitals. We found suggestive association signals between HD eAO and/or mAO and genetic variation within the E2F2, ATF7IP, GRIN2A, GRIN2B, LINC01559, HIP1 and GRIK2 genes. Among them, the most significant was the association between eAO and rs2742976, mapping to the promoter region of E2F2 transcription factor. Furthermore, rs2742976 T allele patient carriers exhibited significantly lower lymphocyte E2F2 gene expression, suggesting a possible implication of E2F2-dependent transcriptional activity in HD pathogenesis. Thus, E2F2 emerges as a new potential HD AO modifier factor.",
+ "publisher": "PLoS currents",
+ "issn": "2157-3999",
+ "date": "2011-10-04",
+ "abstract": "Several candidate modifier genes which, in addition to the pathogenic CAG repeat expansion, influence the age at onset (AO) in Huntington disease (HD) have already been described. The aim of this study was to replicate association of variations in the N-methyl D-aspartate receptor subtype genes GRIN2A and GRIN2B in the \"REGISTRY\" cohort from the European Huntington Disease Network (EHDN). The analyses did replicate the association reported between the GRIN2A rs2650427 variation and AO in the entire cohort. Yet, when subjects were stratified by AO subtypes, we found nominally significant evidence for an association of the GRIN2A rs1969060 variation and the GRIN2B rs1806201 variation. These findings further implicate the N-methyl D-aspartate receptor subtype genes as loci containing variation associated with AO in HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26148071"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21989477"
},
{
- "id": "pmid:26148061",
+ "id": "pmid:21962718",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26148061",
- "title": "Structural Insights Reveal the Dynamics of the Repeating r(CAG) Transcript Found in Huntington's Disease (HD) and Spinocerebellar Ataxias (SCAs).",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21962718",
+ "title": "Clinical and genetic characteristics in patients with Huntington's Disease from Argentina.",
"type": "article-journal",
- "doi": "10.1371/journal.pone.0131788",
+ "doi": "10.1016/j.parkreldis.2011.09.011",
"authors": [
- ["Arpita", "Tawani"],
- ["Amit", "Kumar"]
+ ["Emilia", "Gatto"],
+ ["Virginia", "Parisi"],
+ ["Gabriel", "Persi"],
+ ["Daniela Paola", "Converso"],
+ ["Jos\u00e9 Luis", "Etcheverry"],
+ ["Viviana", "Varela"],
+ ["Ariel", "Lopez"],
+ ["Liliana", "Alba"],
+ ["Gustavo", "Fretchel"]
],
- "publisher": "PloS one",
- "issn": "1932-6203",
- "date": "2015-07-06",
- "abstract": "In humans, neurodegenerative disorders such as Huntington's disease (HD) and many spinocerebellar ataxias (SCAs) have been found to be associated with CAG trinucleotide repeat expansion. An important RNA-mediated mechanism that causes these diseases involves the binding of the splicing regulator protein MBNL1 (Muscleblind-like 1 protein) to expanded r(CAG) repeats. Moreover, mutant huntingtin protein translated from expanded r(CAG) also yields toxic effects. To discern the role of mutant RNA in these diseases, it is essential to gather information about its structure. Detailed insight into the different structures and conformations adopted by these mutant transcripts is vital for developing therapeutics targeting them. Here, we report the crystal structure of an RNA model with a r(CAG) motif, which is complemented by an NMR-based solution structure obtained from restrained Molecular Dynamics (rMD) simulation studies. Crystal structure data of the RNA model resolved at 2.3 \u00c5 reveals non-canonical pairing of adenine in 5\u00b4-CAG/3\u00b4-GAC motif samples in different syn and anti conformations. The overall RNA structure has helical parameters intermediate to the A- and B-forms of nucleic acids due to the global widening of major grooves and base-pair preferences near internal AA loops. The comprehension of structural behaviour by studying the spectral features and the dynamics also supports the flexible nature of the r(CAG) motif.",
+ "publisher": "Parkinsonism & related disorders",
+ "issn": "1873-5126",
+ "date": "2011-10-01",
+ "abstract": "Huntington's Disease (HD) is a neurodegenerative disease, caused by the expansion of an unstable (CAG)(n) in the HTT gene. There is scarce data about the disease in Argentina.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26148061"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21962718"
},
{
- "id": "pmid:26081309",
+ "id": "pmid:21907324",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26081309",
- "title": "Psychiatric and cognitive symptoms in Huntington's disease are modified by polymorphisms in catecholamine regulating enzyme genes.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21907324",
+ "title": "Striatal volume contributes to the prediction of onset of Huntington disease in incident cases.",
"type": "article-journal",
- "doi": "10.1111/cge.12628",
+ "doi": "10.1016/j.biopsych.2011.07.030",
"authors": [
- ["T", "Vinther-Jensen"],
- ["T T", "Nielsen"],
- ["E", "Budtz-J\u00f8rgensen"],
- ["I U", "Larsen"],
- ["M M", "Hansen"],
- ["L", "Hasholt"],
- ["L E", "Hjermind"],
- ["J E", "Nielsen"],
- ["A", "N\u00f8rrem\u00f8lle"]
+ ["Elizabeth H", "Aylward"],
+ ["Dawei", "Liu"],
+ ["Peggy C", "Nopoulos"],
+ ["Christopher A", "Ross"],
+ ["Ronald K", "Pierson"],
+ ["James A", "Mills"],
+ ["Jeffrey D", "Long"],
+ ["Jane S", "Paulsen"]
],
- "publisher": "Clinical genetics",
- "issn": "1399-0004",
- "date": "2015-07-17",
- "abstract": "Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder characterized by motor, psychiatric, and cognitive manifestations. HD is caused by a CAG repeat expansion in the Huntingtin (HTT) gene but the exact pathogenesis remains unknown. Dopamine imbalance has previously been shown in HD, and furthermore dopamine is thought to be implicated in cognition, behavioral and motor disturbances. A substantiated inverse correlation between motor onset and the elongated CAG repeat in the HTT has been established. This relation does not account for the full variability of the motor onset, and efforts have been put into finding genetic modifiers of motor onset, however, mostly with unsuccessful outcome. In this study, we took an alternative approach focusing on symptom complexes and searched for modifiers of cognitive impairment and psychiatric symptoms in a well-described cohort of Danish HD gene-expansion carriers. We show that cognitive impairment and psychiatric symptoms in HD are modified by polymorphisms in the monoamine oxidase A (MAOA) and catechol-O-methyltransferase (COMT) genes and by the 4p16.3 B haplotype. These results support the theory of dopamine imbalance in HD, and point toward more personalized treatment modalities of HD in the future.",
+ "publisher": "Biological psychiatry",
+ "issn": "1873-2402",
+ "date": "2011-09-09",
+ "abstract": "Previous neuroimaging research indicates that brain atrophy in Huntington disease (HD) begins many years before movement abnormalities become severe enough to warrant diagnosis. Most clinical trials being planned for individuals in the prediagnostic stage of HD propose to use delay of disease onset as the primary outcome measure. Although formulas have been developed based on age and CAG repeat length, to predict when HD motor onset will occur, it would be useful to have additional measures that can improve the accuracy of prediction of disease onset.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26081309"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21907324"
},
{
- "id": "pmid:25990798",
+ "id": "pmid:21897851",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25990798",
- "title": "Transfer of genetic therapy across human populations: molecular targets for increasing patient coverage in repeat expansion diseases.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21897851",
+ "title": "Quantification of age-dependent somatic CAG repeat instability in Hdh CAG knock-in mice reveals different expansion dynamics in striatum and liver.",
"type": "article-journal",
- "doi": "10.1038/ejhg.2015.94",
+ "doi": "10.1371/journal.pone.0023647",
"authors": [
- ["Miguel A", "Varela"],
- ["Helen J", "Curtis"],
- ["Andrew G L", "Douglas"],
- ["Suzan M", "Hammond"],
- ["Aisling J", "O'Loughlin"],
- ["Maria J", "Sobrido"],
- ["Janine", "Scholefield"],
- ["Matthew J A", "Wood"]
+ ["Jong-Min", "Lee"],
+ ["Ricardo Mouro", "Pinto"],
+ ["Tammy", "Gillis"],
+ ["Jason C", "St Claire"],
+ ["Vanessa C", "Wheeler"]
],
- "publisher": "European journal of human genetics : EJHG",
- "issn": "1476-5438",
- "date": "2015-05-20",
- "abstract": "Allele-specific gene therapy aims to silence expression of mutant alleles through targeting of disease-linked single-nucleotide polymorphisms (SNPs). However, SNP linkage to disease varies between populations, making such molecular therapies applicable only to a subset of patients. Moreover, not all SNPs have the molecular features necessary for potent gene silencing. Here we provide knowledge to allow the maximisation of patient coverage by building a comprehensive understanding of SNPs ranked according to their predicted suitability toward allele-specific silencing in 14 repeat expansion diseases: amyotrophic lateral sclerosis and frontotemporal dementia, dentatorubral-pallidoluysian atrophy, myotonic dystrophy 1, myotonic dystrophy 2, Huntington's disease and several spinocerebellar ataxias. Our systematic analysis of DNA sequence variation shows that most annotated SNPs are not suitable for potent allele-specific silencing across populations because of suboptimal sequence features and low variability (>97% in HD). We suggest maximising patient coverage by selecting SNPs with high heterozygosity across populations, and preferentially targeting SNPs that lead to purine:purine mismatches in wild-type alleles to obtain potent allele-specific silencing. We therefore provide fundamental knowledge on strategies for optimising patient coverage of therapeutics for microsatellite expansion disorders by linking analysis of population genetic variation to the selection of molecular targets.",
+ "publisher": "PloS one",
+ "issn": "1932-6203",
+ "date": "2011-08-29",
+ "abstract": "Age at onset of Huntington's disease (HD) is largely determined by the CAG trinucleotide repeat length in the HTT gene. Importantly, the CAG repeat undergoes tissue-specific somatic instability, prevalent in brain regions that are disease targets, suggesting a potential role for somatic CAG repeat instability in modifying HD pathogenesis. Thus, understanding underlying mechanisms of somatic CAG repeat instability may lead to discoveries of novel therapeutics for HD. Investigation of the dynamics of the CAG repeat size changes over time may provide insights into the mechanisms underlying CAG repeat instability.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25990798"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21897851"
},
{
- "id": "pmid:25972145",
+ "id": "pmid:21896309",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25972145",
- "title": "In Vitro Differentiation of Human Neural Progenitor Cells Into Striatal GABAergic Neurons.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21896309",
+ "title": "Protective role of the ubiquitin binding protein Tollip against the toxicity of polyglutamine-expansion proteins.",
"type": "article-journal",
- "doi": "10.5966/sctm.2014-0083",
+ "doi": "10.1016/j.neulet.2011.08.043",
"authors": [
- ["Lin", "Lin"],
- ["Juan", "Yuan"],
- ["Bjoern", "Sander"],
- ["Monika M", "Golas"]
+ ["Asami", "Oguro"],
+ ["Hiroshi", "Kubota"],
+ ["Miho", "Shimizu"],
+ ["Shoichi", "Ishiura"],
+ ["Yoriko", "Atomi"]
],
- "publisher": "Stem cells translational medicine",
- "issn": "2157-6564",
- "date": "2015-05-13",
- "abstract": ": Huntington's disease (HD) results from a CAG repeat expansion in the gene encoding the huntingtin protein. This inherited disorder is characterized by progressive neurodegeneration. In particular, HD progression involves the loss of striatal projection neurons. The limited availability of reliable sources of human striatal projection neurons currently hampers our understanding of HD mechanisms and hinders the development of novel HD treatments. In this paper, we described two- and three-step methods for differentiating human neural progenitor cells toward striatal projection neurons. In the two-step differentiation protocol, 90%, 54%, and 6% of MAP2-positive cells were immunopositive for GABA, calbindin (CALB1), and DARPP-32/PPP1R1B, respectively. In the three-step differentiation protocol, 96%, 84%, and 21% of MAP2-positive cells were immunopositive for GABA, calbindin, and DARPP-32/PPP1R1B, respectively. In line with a striatal projection neuron phenotype, cells differentiated with our protocols displayed significantly increased expression of MAP2, CALB1, DARPP-32/PPP1R1B, ARPP21, and CTIP2. Application of glutamate receptor agonists induced calcium influx; accordingly, the cells also expressed various ionotropic glutamate receptor subunits. Differentiated cells also released GABA on stimulation. We suggest that our three-step differentiation protocol presents a reliable and simplified method for the generation of striatal projection neurons, yielding a critical resource for neuronal physiology and neurodegenerative disorder studies.",
+ "publisher": "Neuroscience letters",
+ "issn": "1872-7972",
+ "date": "2011-08-27",
+ "abstract": "Huntington disease (HD) is caused by the expansion of polyglutamine (polyQ) repeats in the amino-terminal of hungtintin (htt). PolyQ-expanded htt forms intracellular ubiquitinated aggregates in neurons and causes neuronal cell death. Here, utilizing a HD cellular model, we report that Tollip, an ubiquitin binding protein that participates in intracellular transport via endosomes, co-localizes with and stimulates aggregation of polyQ-expanded amino-terminal htt. Furthermore, we demonstrate that Tollip protects cells against the toxicity of polyQ-expanded htt. We propose that association of Tollip with polyubiquitin accelerates aggregation of toxic htt species into inclusions and thus provides a cell protective role by sequestration.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25972145"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21896309"
},
{
- "id": "pmid:25934536",
+ "id": "pmid:21555070",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25934536",
- "title": "Nocturnal agitation in Huntington disease is caused by arousal-related abnormal movements rather than by rapid eye movement sleep behavior disorder.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21555070",
+ "title": "An antisense CAG repeat transcript at JPH3 locus mediates expanded polyglutamine protein toxicity in Huntington's disease-like 2 mice.",
"type": "article-journal",
- "doi": "10.1016/j.sleep.2014.12.021",
+ "doi": "10.1016/j.neuron.2011.03.021",
"authors": [
- ["Dulce", "Neutel"],
- ["Maya", "Tchikviladz\u00e9"],
- ["Perrine", "Charles"],
- ["Smaranda", "Leu-Semenescu"],
- ["Emmanuel", "Roze"],
- ["Alexandra", "Durr"],
- ["Isabelle", "Arnulf"]
+ ["Brian", "Wilburn"],
+ ["Dobrila D", "Rudnicki"],
+ ["Jing", "Zhao"],
+ ["Tara Murphy", "Weitz"],
+ ["Yin", "Cheng"],
+ ["Xiaofeng", "Gu"],
+ ["Erin", "Greiner"],
+ ["Chang Sin", "Park"],
+ ["Nan", "Wang"],
+ ["Bryce L", "Sopher"],
+ ["Albert R", "La Spada"],
+ ["Alex", "Osmand"],
+ ["Russell L", "Margolis"],
+ ["Yi E", "Sun"],
+ ["X William", "Yang"]
],
- "publisher": "Sleep medicine",
- "issn": "1878-5506",
- "date": "2015-03-03",
- "abstract": "Patients with Huntington disease (HD) and their spouses often complain of agitation during sleep, but the causes are mostly unknown.",
+ "publisher": "Neuron",
+ "issn": "1097-4199",
+ "date": "2011-05-12",
+ "abstract": "Huntington's disease-like-2 (HDL2) is a phenocopy of Huntington's disease caused by CTG/CAG repeat expansion at the Junctophilin-3 (JPH3) locus. The mechanisms underlying HDL2 pathogenesis remain unclear. Here we developed a BAC transgenic mouse model of HDL2 (BAC-HDL2) that exhibits progressive motor deficits, selective neurodegenerative pathology, and ubiquitin-positive nuclear inclusions (NIs). Molecular analyses reveal a promoter at the transgene locus driving the expression of a CAG repeat transcript (HDL2-CAG) from the strand antisense to JPH3, which encodes an expanded polyglutamine (polyQ) protein. Importantly, BAC-HDL2 mice, but not control BAC mice, accumulate polyQ-containing NIs in a pattern strikingly similar to those in the patients. Furthermore, BAC mice with genetic silencing of the expanded CUG transcript still express HDL2-CAG transcript and manifest polyQ pathogenesis. Finally, studies of HDL2 mice and patients revealed CBP sequestration into NIs and evidence for interference of CBP-mediated transcriptional activation. These results suggest overlapping polyQ-mediated pathogenic mechanisms in HD and HDL2.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25934536"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21555070"
},
{
- "id": "pmid:25889241",
+ "id": "pmid:21540131",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25889241",
- "title": "miR-10b-5p expression in Huntington's disease brain relates to age of onset and the extent of striatal involvement.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21540131",
+ "title": "Parent-of-origin differences of mutant HTT CAG repeat instability in Huntington's disease.",
"type": "article-journal",
- "doi": "10.1186/s12920-015-0083-3",
+ "doi": "10.1016/j.ejmg.2011.04.002",
"authors": [
- ["Andrew G", "Hoss"],
- ["Adam", "Labadorf"],
- ["Jeanne C", "Latourelle"],
- ["Vinay K", "Kartha"],
- ["Tiffany C", "Hadzi"],
- ["James F", "Gusella"],
- ["Marcy E", "MacDonald"],
- ["Jiang-Fan", "Chen"],
- ["Schahram", "Akbarian"],
- ["Zhiping", "Weng"],
- ["Jean Paul", "Vonsattel"],
- ["Richard H", "Myers"]
+ ["N Ahmad", "Aziz"],
+ ["Martine J", "van Belzen"],
+ ["Ilona D", "Coops"],
+ ["Ren\u00e9 D M", "Belfroid"],
+ ["Raymund A C", "Roos"]
],
- "publisher": "BMC medical genomics",
- "issn": "1755-8794",
- "date": "2015-03-01",
- "abstract": "MicroRNAs (miRNAs) are small non-coding RNAs that recognize sites of complementarity of target messenger RNAs, resulting in transcriptional regulation and translational repression of target genes. In Huntington's disease (HD), a neurodegenerative disease caused by a trinucleotide repeat expansion, miRNA dyregulation has been reported, which may impact gene expression and modify the progression and severity of HD.",
+ "publisher": "European journal of medical genetics",
+ "issn": "1878-0849",
+ "date": "2011-04-23",
+ "abstract": "Huntington's disease (HD) is a progressive autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion in the HD gene (HTT). The CAG domain of mutant HTT is unstable upon intergenerational transmission, however, little is known about the underlying mechanisms.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25889241"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21540131"
},
{
- "id": "pmid:25876513",
+ "id": "pmid:21519949",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25876513",
- "title": "RTP801 Is Involved in Mutant Huntingtin-Induced Cell Death.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21519949",
+ "title": "Genotype-, aging-dependent abnormal caspase activity in Huntington disease blood cells.",
"type": "article-journal",
- "doi": "10.1007/s12035-015-9166-6",
+ "doi": "10.1007/s00702-011-0646-1",
"authors": [
- ["N\u00faria", "Mart\u00edn-Flores"],
- ["Joan", "Roman\u00ed-Aumedes"],
- ["Laura", "Ru\u00e9"],
- ["Merc\u00e8", "Canal"],
- ["Phil", "Sanders"],
- ["Marco", "Straccia"],
- ["Nicholas D", "Allen"],
- ["Jordi", "Alberch"],
- ["Josep M", "Canals"],
- ["Esther", "P\u00e9rez-Navarro"],
- ["Cristina", "Malagelada"]
+ ["Ferdinando", "Squitieri"],
+ ["Vittorio", "Maglione"],
+ ["Sara", "Orobello"],
+ ["Francesco", "Fornai"]
],
- "publisher": "Molecular neurobiology",
- "issn": "1559-1182",
- "date": "2015-04-16",
- "abstract": "RTP801 expression is induced by cellular stress and has a pro-apoptotic function in non-proliferating differentiated cells such as neurons. In several neurodegenerative disorders, including Parkinson's disease and Alzheimer's disease, elevated levels of RTP801 have been observed, which suggests a role for RTP801 in neuronal death. Neuronal death is also a pathological hallmark in Huntington's disease (HD), an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. Currently, the exact mechanisms underlying mutant huntingtin (mhtt)-induced toxicity are still unclear. Here, we investigated whether RTP801 is involved in (mhtt)-induced cell death. Ectopic exon-1 mhtt elevated RTP801 mRNA and protein levels in nerve growth factor (NGF)-differentiated PC12 cells and in rat primary cortical neurons. In neuronal PC12 cells, mhtt also contributed to RTP801 protein elevation by reducing its proteasomal degradation rate, in addition to promoting RTP801 gene expression. Interestingly, silencing RTP801 expression with short hairpin RNAs (shRNAs) blocked mhtt-induced cell death in NGF-differentiated PC12 cells. However, RTP801 protein levels were not altered in the striatum of Hdh(Q7/Q111) and R6/1 mice, two HD models that display motor deficits but not neuronal death. Importantly, RTP801 protein levels were elevated in both neural telencephalic progenitors differentiated from HD patient-derived induced pluripotent stem cells and in the putamen and cerebellum of human HD postmortem brains. Taken together, our results suggest that RTP801 is a novel downstream effector of mhtt-induced toxicity and that it may be relevant to the human disease.",
+ "publisher": "Journal of neural transmission (Vienna, Austria : 1996)",
+ "issn": "1435-1463",
+ "date": "2011-04-26",
+ "abstract": "Huntington's Disease (HD) is caused by trinucleotide CAG repeat expansion >36 in huntingtin (htt), a protein with several documented functions. The elongated polyglutamine (polyQ) stretch in the N-terminal region of htt leads to dysfunctional and degenerative events in neurons and peripheral tissues. In this study, by extending the analysis to several caspase activities (i.e. caspase 2, 3, 6, 8 and 9), we describe genotype- and time- dependent caspase activity abnormalities, decreased cell viability and a large set of alterations in mitochondria morphology, in cultured blood cells from HD patients. Patients homozygous for CAG repeat mutations and heterozygous with high size mutations causing juvenile onset (JHD) presented significantly increased caspase 2, 3, 6, 8 and 9 activities, decreased cell viability and pronounced morphological abnormalities, compared with cells carrying low mutation size and controls. After cyanide treatment, all caspases increased their activities in homozygous and highly expanded heterozygous cells, caspase 8 and 9 increased also in those cells carrying low-size mutations, remarking their key role as 'caspase initiators' in HD. The remarkable ageing-dependent abnormalities in peripheral cells carrying particularly toxic mutations (i.e. homozygotes' and JHD's blood cells) points out the potential dependence of clinical HD development and progression on either mutated htt dosage or missing wild type htt. Peripheral tissues (i.e. blood cells) may theoretically represent an important tool for studying HD mechanisms and searching for new biomarkers, according to the patients' genotype.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25876513"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21519949"
},
{
- "id": "pmid:25859666",
+ "id": "pmid:21427085",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25859666",
- "title": "Characterization of HTT inclusion size, location, and timing in the zQ175 mouse model of Huntington's disease: an in vivo high-content imaging study.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21427085",
+ "title": "Inhibition of mutant huntingtin expression by RNA duplex targeting expanded CAG repeats.",
"type": "article-journal",
- "doi": "10.1371/journal.pone.0123527",
+ "doi": "10.1093/nar/gkr156",
"authors": [
- ["Nikisha", "Carty"],
- ["Nad\u00e8ge", "Berson"],
- ["Karsten", "Tillack"],
- ["Christina", "Thiede"],
- ["Diana", "Scholz"],
- ["Karsten", "Kottig"],
- ["Yalda", "Sedaghat"],
- ["Christina", "Gabrysiak"],
- ["George", "Yohrling"],
- ["Heinz", "von der Kammer"],
- ["Andreas", "Ebneth"],
- ["Volker", "Mack"],
- ["Ignacio", "Munoz-Sanjuan"],
- ["Seung", "Kwak"]
+ ["Agnieszka", "Fiszer"],
+ ["Agnieszka", "Mykowska"],
+ ["Wlodzimierz J", "Krzyzosiak"]
],
- "publisher": "PloS one",
- "issn": "1932-6203",
- "date": "2015-04-10",
- "abstract": "Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin gene. Major pathological hallmarks of HD include inclusions of mutant huntingtin (mHTT) protein, loss of neurons predominantly in the caudate nucleus, and atrophy of multiple brain regions. However, the early sequence of histological events that manifest in region- and cell-specific manner has not been well characterized. Here we use a high-content histological approach to precisely monitor changes in HTT expression and characterize deposition dynamics of mHTT protein inclusion bodies in the recently characterized zQ175 knock-in mouse line. We carried out an automated multi-parameter quantitative analysis of individual cortical and striatal cells in tissue slices from mice aged 2-12 months and confirmed biochemical reports of an age-associated increase in mHTT inclusions in this model. We also found distinct regional and subregional dynamics for inclusion number, size and distribution with subcellular resolution. We used viral-mediated suppression of total HTT in the striatum of zQ175 mice as an example of a therapeutically-relevant but heterogeneously transducing strategy to demonstrate successful application of this platform to quantitatively assess target engagement and outcome on a cellular basis.",
+ "publisher": "Nucleic acids research",
+ "issn": "1362-4962",
+ "date": "2011-03-22",
+ "abstract": "The specific silencing of the gene of interest is the major objective of RNA interference technology; therefore, unique sequences but not abundant sequence repeats are targeted by silencing reagents. Here, we describe the targeting of expanded CAG repeats that occur in transcripts derived from the mutant allele of the gene implicated in Huntington's disease (HD) in the presence of the normal allele and other human mRNAs containing CAG and CUG repeat tracts. We show that a high degree of silencing selectivity may be achieved between the repeated sequences. We demonstrate preferential suppression of the mutant huntingtin allele and concomitant activation of the normal huntingtin allele in cell lines derived from HD patients that were transfected with short RNA duplexes composed of CAG and CUG repeats containing mutations at specific positions. These effects may lead to promising therapeutic modalities for HD, a condition for which no therapy presently exists.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25859666"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21427085"
},
{
- "id": "pmid:25800750",
+ "id": "pmid:21370269",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25800750",
- "title": "Cardiac Fas-Dependent and Mitochondria-Dependent Apoptotic Pathways in a Transgenic Mouse Model of Huntington's Disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21370269",
+ "title": "An item response analysis of the motor and behavioral subscales of the unified Huntington's disease rating scale in huntington disease gene expansion carriers.",
"type": "article-journal",
- "doi": "10.1007/s12012-015-9318-y",
+ "doi": "10.1002/mds.23574",
"authors": [
- ["Bor-Tsang", "Wu"],
- ["Ming-Chang", "Chiang"],
- ["Ching-Yi", "Tasi"],
- ["Chia-Hua", "Kuo"],
- ["Woei-Cherng", "Shyu"],
- ["Chung-Lan", "Kao"],
- ["Chih-Yang", "Huang"],
- ["Shin-Da", "Lee"]
+ ["Anthony L", "Vaccarino"],
+ ["Karen", "Anderson"],
+ ["Beth", "Borowsky"],
+ ["Kevin", "Duff"],
+ ["Joseph", "Giuliano"],
+ ["Mark", "Guttman"],
+ ["Aileen K", "Ho"],
+ ["Michael", "Orth"],
+ ["Jane S", "Paulsen"],
+ ["Terrence", "Sills"],
+ ["Daniel P", "van Kammen"],
+ ["Kenneth R", "Evans"]
],
- "publisher": "Cardiovascular toxicology",
- "issn": "1559-0259",
- "date": "2016-04-01",
- "abstract": "Huntington's disease is an autosomal dominant neurodegenerative disease caused by a CAG repeat expansion in the huntingtin gene. Heart disease is the second leading cause of death in patients with Huntington's disease. This study was to evaluate whether cardiac Fas-dependent and mitochondria-dependent apoptotic pathways are activated in transgenic mice with Huntington's disease. Sixteen Huntington's disease transgenic mice (HD) and sixteen wild-type (WT) littermates were studied at 10.5\u00a0weeks of age. The cardiac characteristics, myocardial architecture, and two major apoptotic pathways in the excised left ventricle from mice were measured by histopathological analysis, Western blotting, and TUNEL assays. The whole heart weight and the left ventricular weight decreased significantly in the HD group, as compared to the WT group. Abnormal myocardial architecture, enlarged interstitial spaces, and more cardiac TUNEL-positive cells were observed in the HD group. The key components of Fas-dependent apoptosis (TNF-alpha, TNFR1, Fas ligand, Fas death receptors, FADD, activated caspase-8, and activated caspase-3) and the key components of mitochondria-dependent apoptosis (Bax, Bax-to-Bcl-2 ratio, cytosolic cytochrome c, activated caspase-9, and activated caspase-3) increased significantly in the hearts of the HD group. Cardiac Fas-dependent and mitochondria-dependent apoptotic pathways were activated in transgenic mice with Huntington's disease, which might provide one of possible mechanisms to explain why patients with Huntington's disease will develop heart failure.",
+ "publisher": "Movement disorders : official journal of the Movement Disorder Society",
+ "issn": "1531-8257",
+ "date": "2011-03-02",
+ "abstract": "Although the Unified Huntington's Disease Rating Scale (UHDRS) is widely used in the assessment of Huntington disease (HD), the ability of individual items to discriminate individual differences in motor or behavioral manifestations has not been extensively studied in HD gene expansion carriers without a motor-defined clinical diagnosis (ie, prodromal-HD or prHD). To elucidate the relationship between scores on individual motor and behavioral UHDRS items and total score for each subscale, a nonparametric item response analysis was performed on retrospective data from 2 multicenter longitudinal studies. Motor and behavioral assessments were supplied for 737 prHD individuals with data from 2114 visits (PREDICT-HD) and 686 HD individuals with data from 1482 visits (REGISTRY). Option characteristic curves were generated for UHDRS subscale items in relation to their subscale score. In prHD, overall severity of motor signs was low, and participants had scores of 2 or above on very few items. In HD, motor items that assessed ocular pursuit, saccade initiation, finger tapping, tandem walking, and to a lesser extent, saccade velocity, dysarthria, tongue protrusion, pronation/supination, Luria, bradykinesia, choreas, gait, and balance on the retropulsion test were found to discriminate individual differences across a broad range of motor severity. In prHD, depressed mood, anxiety, and irritable behavior demonstrated good discriminative properties. In HD, depressed mood demonstrated a good relationship with the overall behavioral score. These data suggest that at least some UHDRS items appear to have utility across a broad range of severity, although many items demonstrate problematic features.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25800750"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21370269"
},
{
- "id": "pmid:25767004",
+ "id": "pmid:21347256",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25767004",
- "title": "Noninvasive prenatal diagnosis of Huntington disease: detection of the paternally inherited expanded CAG repeat in maternal plasma.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21347256",
+ "title": "Unusual structures are present in DNA fragments containing super-long Huntingtin CAG repeats.",
"type": "article-journal",
- "doi": "10.1002/pd.4593",
+ "doi": "10.1371/journal.pone.0017119",
"authors": [
- ["Jessica M E", "van den Oever"],
- ["Emilia K", "Bijlsma"],
- ["Ilse", "Feenstra"],
- ["Nienke", "Muntjewerff"],
- ["Inge B", "Mathijssen"],
- ["Egbert", "Bakker"],
- ["Martine J", "van Belzen"],
- ["Elles M J", "Boon"]
+ ["Daniel", "Duzdevich"],
+ ["Jinliang", "Li"],
+ ["Jhoon", "Whang"],
+ ["Hirohide", "Takahashi"],
+ ["Kunio", "Takeyasu"],
+ ["David T F", "Dryden"],
+ ["A Jennifer", "Morton"],
+ ["J Michael", "Edwardson"]
],
- "publisher": "Prenatal diagnosis",
- "issn": "1097-0223",
- "date": "2015-04-05",
- "abstract": "With a shift towards noninvasive testing, we have explored and validated the use of noninvasive prenatal diagnosis (NIPD) for Huntington disease (HD).",
+ "publisher": "PloS one",
+ "issn": "1932-6203",
+ "date": "2011-02-11",
+ "abstract": "In the R6/2 mouse model of Huntington's disease (HD), expansion of the CAG trinucleotide repeat length beyond about 300 repeats induces a novel phenotype associated with a reduction in transcription of the transgene.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25767004"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21347256"
},
{
- "id": "pmid:25703232",
+ "id": "pmid:21211002",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25703232",
- "title": "Neonatal iron supplementation potentiates oxidative stress, energetic dysfunction and neurodegeneration in the R6/2 mouse model of Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21211002",
+ "title": "Localization of sequence variations in PGC-1\u03b1 influence their modifying effect in Huntington disease.",
"type": "article-journal",
- "doi": "10.1016/j.redox.2015.02.002",
+ "doi": "10.1186/1750-1326-6-1",
"authors": [
- ["Kiersten L", "Berggren"],
- ["Jianfang", "Chen"],
- ["Julia", "Fox"],
- ["Jonathan", "Miller"],
- ["Lindsay", "Dodds"],
- ["Bryan", "Dugas"],
- ["Liset", "Vargas"],
- ["Amber", "Lothian"],
- ["Erin", "McAllum"],
- ["Irene", "Volitakis"],
- ["Blaine", "Roberts"],
- ["Ashley I", "Bush"],
- ["Jonathan H", "Fox"]
+ ["Hong Van B", "Che"],
+ ["Silke", "Metzger"],
+ ["Esteban", "Portal"],
+ ["Carolin", "Deyle"],
+ ["Olaf", "Riess"],
+ ["Huu Phuc", "Nguyen"]
],
- "publisher": "Redox biology",
- "issn": "2213-2317",
- "date": "2015-02-11",
- "abstract": "Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion that encodes a polyglutamine tract in huntingtin (htt) protein. Dysregulation of brain iron homeostasis, oxidative stress and neurodegeneration are consistent features of the HD phenotype. Therefore, environmental factors that exacerbate oxidative stress and iron dysregulation may potentiate HD. Iron supplementation in the human population is common during infant and adult-life stages. In this study, iron supplementation in neonatal HD mice resulted in deterioration of spontaneous motor running activity, elevated levels of brain lactate and oxidized glutathione consistent with increased energetic dysfunction and oxidative stress, and increased striatal and motor cortical neuronal atrophy, collectively demonstrating potentiation of the disease phenotype. Oxidative stress, energetic, and anatomic markers of degeneration were not affected in wild-type littermate iron-supplemented mice. Further, there was no effect of elevated iron intake on disease outcomes in adult HD mice. We have demonstrated an interaction between the mutant huntingtin gene and iron supplementation in neonatal HD mice. Findings indicate that elevated neonatal iron intake potentiates mouse HD and promotes oxidative stress and energetic dysfunction in brain. Neonatal-infant dietary iron intake level may be an environmental modifier of human HD.",
+ "publisher": "Molecular neurodegeneration",
+ "issn": "1750-1326",
+ "date": "2011-01-06",
+ "abstract": "Huntington disease (HD) is caused by a polyglutamine expansion of more than 35 units in the huntingtin protein. This expanded repeat length inversely correlates with the age-at-onset (AAO), however, additional genetic factors apart from the expanded CAG repeat size are thought to influence the course and the AAO in HD. Until now, among others, the gene encoding PCG-1\u03b1 (PPARGC1A) was shown to modify the AAO in two independent, however small, populations. PGC-1\u03b1 is involved in the induction of various mechanisms regulating mitochondrial biogenesis and oxidative stress defence. Furthermore, several studies have linked impairment of its function and/or its expression to HD pathogenesis. As the identification of distinct modifiers in association studies is largely dependent on the size of the observed population, we investigated nine different single nucleotide polymorphisms (SNPs) in PPARGC1A in order to replicate the disease modifying effect in more than 800 European HD patients and to identify an association with AAO in HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25703232"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21211002"
},
{
- "id": "pmid:25662336",
+ "id": "pmid:21192926",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25662336",
- "title": "Age-, tissue- and length-dependent bidirectional somatic CAG\u2022CTG repeat instability in an allelic series of R6/2 Huntington disease mice.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21192926",
+ "title": "Longitudinal behavioral, cross-sectional transcriptional and histopathological characterization of a knock-in mouse model of Huntington's disease with 140 CAG repeats.",
"type": "article-journal",
- "doi": "10.1016/j.nbd.2015.01.004",
+ "doi": "10.1016/j.expneurol.2010.12.017",
"authors": [
- ["Eloise", "Larson"],
- ["Ian", "Fyfe"],
- ["A Jennifer", "Morton"],
- ["Darren G", "Monckton"]
+ ["Aaron C", "Rising"],
+ ["Jia", "Xu"],
+ ["Aaron", "Carlson"],
+ ["Vincent V", "Napoli"],
+ ["Eileen M", "Denovan-Wright"],
+ ["Ronald J", "Mandel"]
],
- "publisher": "Neurobiology of disease",
- "issn": "1095-953X",
- "date": "2015-02-03",
- "abstract": "The expansion of simple sequence CAG\u2022CTG repeats is associated with a number of inherited disorders including Huntington disease (HD), myotonic dystrophy type 1 and several of the spinocerebellar ataxias. Inherited disease-associated alleles usually exceed 40 repeats and may be in excess of 1,000 repeats in some disorders. Inherited allele length is inversely proportional to age at onset, and frequent germline expansions account for the striking anticipation observed in affected families. Expanded disease associated alleles are also somatically unstable via a pathway that is age dependent and tissue specific, and also appears to be expansion biased. Somatic expansions are thought to contribute toward both tissue specificity and disease progression. Here we have examined the somatic mutational dynamics in brain and peripheral tissues from an allelic series of R6/2 HD transgenic mice inheriting from 52 to >700 CAG repeats. We found age-dependent, tissue-specific somatic instability, with particularly large expansions observed in the striatum and cortex. We also found a positive increase in somatic instability with increasing allele length. Surprisingly, however, the degree of somatic variation did not increase in a linear fashion, but leveled off with increasing allele length. Most unexpectedly, the almost exclusive bias toward the accumulation of expansions observed in mice inheriting smaller alleles was lost, and a high frequency of large somatic contractions was observed in mice inheriting very large alleles (>500 repeats). These data highlight the bidirectional nature of CAG\u2022CTG repeat instability and the subtle balance that exists between expansion and contraction in vivo. Defining the dynamics and tissue specificity of expansion and contraction is important for understanding the role of genetic instability in pathophysiology and in particular the development of novel therapies based on suppressing expansions and/or promoting contractions.",
+ "publisher": "Experimental neurology",
+ "issn": "1090-2430",
+ "date": "2010-12-28",
+ "abstract": "The discovery of the gene mutation responsible for Huntington's disease (HD), huntingtin, in 1993 allowed for a better understanding of the pathology of and enabled the development of animal models. HD is caused by the expansion of a polyglutamine repeat region in the N-terminal of the huntingtin protein. Here we examine the behavioral, transcriptional, histopathological and anatomical characteristics of a knock-in HD mouse model with a 140 polyglutamine expansion in the huntingtin protein. This CAG 140 model contains a portion of the human exon 1 with 140 CAG repeats knocked into the mouse huntingtin gene. We have longitudinally examined the rearing behavior, accelerating rotarod, constant speed rotarod and gait for age-matched heterozygote, homozygote and non-transgenic mice and have found a significant difference in the afflicted mice. However, while there were significant differences between the non-transgenic and the knock-in mice, these behaviors were not progressive. As in HD, we show that the CAG 140 mice also have a significant decrease in striatally enriched mRNA transcripts. In addition, striatal neuronal intranuclear inclusion density increases with age. Lastly these CAG 140 mice show slight cortical thinning compared to non-transgenic mice, similarly to the cortical thinning recently reported in HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25662336"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21192926"
},
{
- "id": "pmid:25642374",
+ "id": "pmid:22832606",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25642374",
- "title": "Trinucleotide repeats and haplotypes at the huntingtin locus in an Indian sample overlaps with European haplogroup a.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22832606",
+ "title": "Simultaneous genotyping of multiple polymorphisms in human serotonin transporter gene and detection of novel allelic variants.",
"type": "article-journal",
- "doi": "10.1371/currents.hd.a3ad1a381ab1eed117675145318c9a80",
+ "doi": "10.1038/tp.2011.34",
"authors": [
- ["Nagaraj S", "Moily"],
- ["Lakshmi Narayanan", "Kota"],
- ["Ram Murthy", "Anjanappa"],
- ["Sowmya", "Venugopal"],
- ["Radhika", "Vaidyanathan"],
- ["Pramod", "Pal"],
- ["Meera", "Purushottam"],
- ["Sanjeev", "Jain"],
- ["Mahesh", "Kandasamy"]
- ],
- "publisher": "PLoS currents",
- "issn": "2157-3999",
- "date": "2014-09-24",
- "abstract": "Huntington's disease (HD), an autosomal dominant neurodegenerative syndrome, has a world-wide distribution. An estimated 2.5-10/100,000 people of European ancestry are affected with HD, while the Asian populations have lower prevalence (0.6-3.8/100,000). The epidemiology of HD is not well described in India, and the distribution of the pathogenic CAG expansion, and the associated haplotype, in this population needs to be better understood. This study demonstrates a distribution of CAG repeats, at the HTT locus, comparable to the European population in both normal and HD affected chromosomes. Further, we provide an evidence for similarity of the HD halpotype in Indian sample to the European HD haplogroup.",
+ ["R", "Avula"],
+ ["A", "Rand"],
+ ["J L", "Black"],
+ ["D J", "O'Kane"]
+ ],
+ "publisher": "Translational psychiatry",
+ "issn": "2158-3188",
+ "date": "2011-08-16",
+ "abstract": "The serotonin transporter, called SLC6A4, SERT or 5-HTT, modulates neurotransmission by removal of serotonin from the synapse of serotonergic neurons, facilitating serotonin reuptake into the presynaptic terminus. Selective serotonin reuptake inhibitors block the action of the serotonin transporter and are used to treat depression and other neuropsychiatric disorders. Three polymorphisms in the 5-HTT gene have been implicated in treatment response and neuropsychiatric disorders. A 44-bp promoter ins/del polymorphism (5-HTTLPR) produces primarily long and/or short alleles due to either 14 (short) or 16 (long) repeats of variably conserved 20-23 bp units. Also implicated, a 17-18 bp variable number tandem repeat found in intron2 (StIn2) is expressed as triallelic content with 9, 10, or 12 repeats (StIn2.9, StIn2.10 or StIn2.12). Finally, a single nucleotide polymorphism rs25531 located within the promoter polymorphic-linked region alters the function of the long promoter allele. We developed a PCR-based fragment analysis assay, which is analyzed on an ABI sequencer, whereby we are able to detect all three genotypes simultaneously. Using this technique, we identified novel sequences, which demonstrate promoter repeat regions containing (1) a 17 repeat with rs25531 A/G polymorphism, (2) two with 18-repeat units, (3) one with 20-repeat units and (4) a 24-repeat sequence. The novel repeats were confirmed by direct sequencing of gel-purified amplicons.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25642374"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22832606"
},
{
- "id": "pmid:25574027",
+ "id": "pmid:21147489",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25574027",
- "title": "Htt CAG repeat expansion confers pleiotropic gains of mutant huntingtin function in chromatin regulation.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21147489",
+ "title": "The neurology and natural history of patients with indeterminate CAG repeat length mutations of the Huntington disease gene.",
"type": "article-journal",
- "doi": "10.1093/hmg/ddv006",
+ "doi": "10.1016/j.jns.2010.11.015",
"authors": [
- ["Marta", "Biagioli"],
- ["Francesco", "Ferrari"],
- ["Eric M", "Mendenhall"],
- ["Yijing", "Zhang"],
- ["Serkan", "Erdin"],
- ["Ravi", "Vijayvargia"],
- ["Sonia M", "Vallabh"],
- ["Nicole", "Solomos"],
- ["Poornima", "Manavalan"],
- ["Ashok", "Ragavendran"],
- ["Fatih", "Ozsolak"],
- ["Jong Min", "Lee"],
- ["Michael E", "Talkowski"],
- ["James F", "Gusella"],
- ["Marcy E", "Macdonald"],
- ["Peter J", "Park"],
- ["Ihn Sik", "Seong"]
+ ["Peter K", "Panegyres"],
+ ["Judy G S", "Goh"]
],
- "publisher": "Human molecular genetics",
- "issn": "1460-2083",
- "date": "2015-01-08",
- "abstract": "The CAG repeat expansion in the Huntington's disease gene HTT extends a polyglutamine tract in mutant huntingtin that enhances its ability to facilitate polycomb repressive complex 2 (PRC2). To gain insight into this dominant gain of function, we mapped histone modifications genome-wide across an isogenic panel of mouse embryonic stem cell (ESC) and neuronal progenitor cell (NPC) lines, comparing the effects of Htt null and different size Htt CAG mutations. We found that Htt is required in ESC for the proper deposition of histone H3K27me3 at a subset of 'bivalent' loci but in NPC it is needed at 'bivalent' loci for both the proper maintenance and the appropriate removal of this mark. In contrast, Htt CAG size, though changing histone H3K27me3, is prominently associated with altered histone H3K4me3 at 'active' loci. The sets of ESC and NPC genes with altered histone marks delineated by the lack of huntingtin or the presence of mutant huntingtin, though distinct, are enriched in similar pathways with apoptosis specifically highlighted for the CAG mutation. Thus, the manner by which huntingtin function facilitates PRC2 may afford mutant huntingtin with multiple opportunities to impinge upon the broader machinery that orchestrates developmentally appropriate chromatin status.",
+ "publisher": "Journal of the neurological sciences",
+ "issn": "1878-5883",
+ "date": "2010-12-13",
+ "abstract": "This study aims to understand the neurological manifestations of patients with an indeterminate CAG repeat length (36-39) of the Huntingtin gene, HTT.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25574027"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21147489"
},
{
- "id": "pmid:25464109",
+ "id": "pmid:21106039",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25464109",
- "title": "A new mutation for Huntington disease following maternal transmission of an intermediate allele.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21106039",
+ "title": "Functional increase of brain histaminergic signaling in Huntington's disease.",
"type": "article-journal",
- "doi": "10.1016/j.ejmg.2014.11.005",
+ "doi": "10.1111/j.1750-3639.2010.00465.x",
"authors": [
- ["Alicia", "Semaka"],
- ["Chris", "Kay"],
- ["Ren\u00e9 D M", "Belfroid"],
- ["Emilia K", "Bijlsma"],
- ["Monique", "Losekoot"],
- ["Irene M", "van Langen"],
- ["Merel C", "van Maarle"],
- ["Mayke", "Oosterloo"],
- ["Michael R", "Hayden"],
- ["Martine J", "van Belzen"]
+ ["Daniel J", "van Wamelen"],
+ ["Ling", "Shan"],
+ ["N Ahmad", "Aziz"],
+ ["Jasper J", "Anink"],
+ ["Ai-Min", "Bao"],
+ ["Raymund A C", "Roos"],
+ ["Dick F", "Swaab"]
],
- "publisher": "European journal of medical genetics",
- "issn": "1878-0849",
- "date": "2014-11-20",
- "abstract": "New mutations for Huntington disease (HD) originate from CAG repeat expansion of intermediate alleles (27-35 CAG). Expansions of such alleles into the pathological range (\u2265 36 CAG) have been exclusively observed in paternal transmission. We report the occurrence of a new mutation that defies the paternal expansion bias normally observed in HD. A maternal intermediate allele with 33 CAG repeats expanded in transmission to 48 CAG repeats causing a de novo case of HD in the family. Retrospectively, the mother presented with cognitive decline, but HD was never considered in the differential diagnosis. She was diagnosed with dementia and testing for HD was only performed after her daughter had been diagnosed. This observation of an intermediate allele expanding into the full penetrance HD range after maternal transmission has important implications for genetic counselling of females with intermediate repeats.",
+ "publisher": "Brain pathology (Zurich, Switzerland)",
+ "issn": "1750-3639",
+ "date": "2010-12-27",
+ "abstract": "To evaluate whether central histaminergic signaling in Huntington's disease (HD) patients is affected, we assessed mRNA levels of histidine decarboxylase (HDC), volume of and neuron number in the hypothalamic tuberomamillary nucleus (TMN) (HD n = 8, controls n = 8). In addition, we assessed histamine N-methyltransferase (HMT) and histamine receptor (H(1) R, H(2) R and H(3) R) mRNA levels in the inferior frontal gyrus (IFG) (n = 9 and 9) and caudate nucleus (CN) (n = 6 and 6) by real-time polymerase chain reaction. In HD patients, TMN volume and neuronal number was unaltered (P = 0.72, P = 0.25). The levels of HDC mRNA (P = 0.046), IFG HMT (P < 0.001), H(1) R (P < 0.001) and H(3) R mRNA levels (P = 0.011) were increased, while CN H(2) R and H(3) R mRNA levels were decreased (P = 0.041, P = 0.009). In HD patients, we observed a positive correlation between IFG H(3) R mRNA levels and CAG repeat length (P = 0.024) and negative correlations between age at onset of disease and IFG HMT (P = 0.015) and H(1) R (P = 0.021) mRNA levels. These findings indicate a functional increase in brain histaminergic signaling in HD, and provide a rationale for the use of histamine receptor antagonists.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25464109"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21106039"
},
{
- "id": "pmid:25453459",
+ "id": "pmid:21068430",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25453459",
- "title": "Prediction of manifest Huntington's disease with clinical and imaging measures: a prospective observational study.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21068430",
+ "title": "Tapping linked to function and structure in premanifest and symptomatic Huntington disease.",
"type": "article-journal",
- "doi": "10.1016/s1474-4422(14)70238-8",
+ "doi": "10.1212/wnl.0b013e3182020123",
"authors": [
- ["Jane S", "Paulsen"],
- ["Jeffrey D", "Long"],
- ["Christopher A", "Ross"],
- ["Deborah L", "Harrington"],
- ["Cheryl J", "Erwin"],
- ["Janet K", "Williams"],
- ["Holly James", "Westervelt"],
- ["Hans J", "Johnson"],
- ["Elizabeth H", "Aylward"],
- ["Ying", "Zhang"],
- ["H Jeremy", "Bockholt"],
- ["Roger A", "Barker"]
+ ["N", "Bechtel"],
+ ["R I", "Scahill"],
+ ["H D", "Rosas"],
+ ["T", "Acharya"],
+ ["S J A", "van den Bogaard"],
+ ["C", "Jauffret"],
+ ["M J", "Say"],
+ ["A", "Sturrock"],
+ ["H", "Johnson"],
+ ["C E", "Onorato"],
+ ["D H", "Salat"],
+ ["A", "Durr"],
+ ["B R", "Leavitt"],
+ ["R A C", "Roos"],
+ ["G B", "Landwehrmeyer"],
+ ["D R", "Langbehn"],
+ ["J C", "Stout"],
+ ["S J", "Tabrizi"],
+ ["R", "Reilmann"]
],
- "publisher": "The Lancet. Neurology",
- "issn": "1474-4465",
- "date": "2014-11-03",
- "abstract": "Although the association between cytosine-adenine-guanine (CAG) repeat length and age at onset of Huntington's disease is well known, improved prediction of onset would be advantageous for clinical trial design and prognostic counselling. We compared various measures for tracking progression and predicting conversion to manifest Huntington's disease.",
+ "publisher": "Neurology",
+ "issn": "1526-632X",
+ "date": "2010-11-10",
+ "abstract": "Motor signs are functionally disabling features of Huntington disease. Characteristic motor signs define disease manifestation. Their severity and onset are assessed by the Total Motor Score of the Unified Huntington's Disease Rating Scale, a categorical scale limited by interrater variability and insensitivity in premanifest subjects. More objective, reliable, and precise measures are needed which permit clinical trials in premanifest populations. We hypothesized that motor deficits can be objectively quantified by force-transducer-based tapping and correlate with disease burden and brain atrophy.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25453459"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21068430"
},
{
- "id": "pmid:25385587",
+ "id": "pmid:20935170",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25385587",
- "title": "Potential function for the Huntingtin protein as a scaffold for selective autophagy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/20935170",
+ "title": "Huntington's and myotonic dystrophy hESCs: down-regulated trinucleotide repeat instability and mismatch repair machinery expression upon differentiation.",
"type": "article-journal",
- "doi": "10.1073/pnas.1420103111",
+ "doi": "10.1093/hmg/ddq456",
"authors": [
- ["Joseph", "Ochaba"],
- ["Tam\u00e1s", "Lukacsovich"],
- ["George", "Csikos"],
- ["Shuqiu", "Zheng"],
- ["Julia", "Margulis"],
- ["Lisa", "Salazar"],
- ["Kai", "Mao"],
- ["Alice L", "Lau"],
- ["Sylvia Y", "Yeung"],
- ["Sandrine", "Humbert"],
- ["Fr\u00e9d\u00e9ric", "Saudou"],
- ["Daniel J", "Klionsky"],
- ["Steven", "Finkbeiner"],
- ["Scott O", "Zeitlin"],
- ["J Lawrence", "Marsh"],
- ["David E", "Housman"],
- ["Leslie M", "Thompson"],
- ["Joan S", "Steffan"]
+ ["Anna", "Seriola"],
+ ["Claudia", "Spits"],
+ ["Jodie P", "Simard"],
+ ["Pierre", "Hilven"],
+ ["Patrick", "Haentjens"],
+ ["Christopher E", "Pearson"],
+ ["Karen", "Sermon"]
],
- "publisher": "Proceedings of the National Academy of Sciences of the United States of America",
- "issn": "1091-6490",
- "date": "2014-11-10",
- "abstract": "Although dominant gain-of-function triplet repeat expansions in the Huntingtin (HTT) gene are the underlying cause of Huntington disease (HD), understanding the normal functions of nonmutant HTT protein has remained a challenge. We report here findings that suggest that HTT plays a significant role in selective autophagy. Loss of HTT function in Drosophila disrupts starvation-induced autophagy in larvae and conditional knockout of HTT in the mouse CNS causes characteristic cellular hallmarks of disrupted autophagy, including an accumulation of striatal p62/SQSTM1 over time. We observe that specific domains of HTT have structural similarities to yeast Atg proteins that function in selective autophagy, and in particular that the C-terminal domain of HTT shares structural similarity to yeast Atg11, an autophagic scaffold protein. To explore possible functional similarity between HTT and Atg11, we investigated whether the C-terminal domain of HTT interacts with mammalian counterparts of yeast Atg11-interacting proteins. Strikingly, this domain of HTT coimmunoprecipitates with several key Atg11 interactors, including the Atg1/Unc-51-like autophagy activating kinase 1 kinase complex, autophagic receptor proteins, and mammalian Atg8 homologs. Mutation of a phylogenetically conserved WXXL domain in a C-terminal HTT fragment reduces coprecipitation with mammalian Atg8 homolog GABARAPL1, suggesting a direct interaction. Collectively, these data support a possible central role for HTT as an Atg11-like scaffold protein. These findings have relevance to both mechanisms of disease pathogenesis and to therapeutic intervention strategies that reduce levels of both mutant and normal HTT.",
+ "publisher": "Human molecular genetics",
+ "issn": "1460-2083",
+ "date": "2010-10-08",
+ "abstract": "Huntington's disease (HD) and myotonic dystrophy (DM1) are caused by trinucleotide repeat expansions. The repeats show different instability patterns according to the disorder, cell type and developmental stage. Here we studied the behavior of these repeats in DM1- and HD-derived human embryonic stem cells (hESCs) before and after differentiation, and its relationship to the DNA mismatch repair (MMR). The relatively small (CAG)44 HD expansion was stable in undifferentiated and differentiated HD hESCs. In contrast, the DM1 repeat showed instability from the earliest passages onwards in DM1 hESCs with (CTG)250 or (CTG)1800. Upon differentiation the DM1 repeat was stabilized. MMR genes, including hMSH2, hMSH3 and hMSH6 were assessed at the transcript and protein levels in differentiated cells. The coincidence of differentiation-induced down-regulated MMR expression with reduced instability of the long expanded repeats in hESCs is consistent with a known requirement of MMR proteins for repeat instability in transgenic mice. This is the first demonstration of a correlation between altered repeat instability of an endogenous DM1 locus and natural MMR down-regulation, in contrast to the commonly used murine knock-down systems.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25385587"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20935170"
},
{
- "id": "pmid:25322077",
+ "id": "pmid:20919768",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25322077",
- "title": "The phosphodiesterase 10 positron emission tomography tracer, [18F]MNI-659, as a novel biomarker for early Huntington disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/20919768",
+ "title": "Neurocognitive signs in prodromal Huntington disease.",
"type": "article-journal",
- "doi": "10.1001/jamaneurol.2014.1954",
+ "doi": "10.1037/a0020937",
"authors": [
- ["David S", "Russell"],
- ["Olivier", "Barret"],
- ["Danna L", "Jennings"],
- ["Joseph H", "Friedman"],
- ["Gilles D", "Tamagnan"],
- ["David", "Thomae"],
- ["David", "Alagille"],
- ["Thomas J", "Morley"],
- ["Caroline", "Papin"],
- ["Spyridon", "Papapetropoulos"],
- ["Rikki N", "Waterhouse"],
- ["John P", "Seibyl"],
- ["Kenneth L", "Marek"]
+ ["Julie C", "Stout"],
+ ["Jane S", "Paulsen"],
+ ["Sarah", "Queller"],
+ ["Andrea C", "Solomon"],
+ ["Kathryn B", "Whitlock"],
+ ["J Colin", "Campbell"],
+ ["Noelle", "Carlozzi"],
+ ["Kevin", "Duff"],
+ ["Leigh J", "Beglinger"],
+ ["Douglas R", "Langbehn"],
+ ["Shannon A", "Johnson"],
+ ["Kevin M", "Biglan"],
+ ["Elizabeth H", "Aylward"]
],
- "publisher": "JAMA neurology",
- "issn": "2168-6157",
- "date": "2014-12-01",
- "abstract": "In Huntington disease (HD) striatal neuron loss precedes and predicts motor signs or symptoms. Current imaging biomarkers lack adequate sensitivity for assessing the early stages of HD. Developing an imaging biomarker for HD spanning the time of onset of motor signs remains a major unmet research need. Intracellular proteins whose expression is altered by the mutant huntingtin protein may be superior markers for early HD stages.",
+ "publisher": "Neuropsychology",
+ "issn": "1931-1559",
+ "date": "2011-01-01",
+ "abstract": "PREDICT-HD is a large-scale international study of people with the Huntington disease (HD) CAG-repeat expansion who are not yet diagnosed with HD. The objective of this study was to determine the stage in the HD prodrome at which cognitive differences from CAG-normal controls can be reliably detected.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25322077"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20919768"
},
{
- "id": "pmid:25316307",
+ "id": "pmid:24868381",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25316307",
- "title": "Sexually dimorphic dopaminergic dysfunction in a transgenic mouse model of Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/24868381",
+ "title": "A case of juvenile huntington disease in a 6-year-old boy.",
"type": "article-journal",
- "doi": "10.1016/j.pbb.2014.10.004",
+ "doi": "10.14802/jmd.10012",
"authors": [
- ["Thibault", "Renoir"],
- ["Andrew", "Argyropoulos"],
- ["Caroline", "Chevarin"],
- ["Laurence", "Lanfumey"],
- ["Anthony J", "Hannan"]
+ ["Jun-Sang", "Sunwoo"],
+ ["Soon-Tae", "Lee"],
+ ["Manho", "Kim"]
],
- "publisher": "Pharmacology, biochemistry, and behavior",
- "issn": "1873-5177",
- "date": "2014-10-12",
- "abstract": "Using the R6/1 transgenic mouse model of Huntington's disease (HD), we have recently shown that acute administration with the dopamine-norepinephrine reuptake inhibitor bupropion was able to rescue depressive-like behaviours in female HD mice at 12weeks of age.",
+ "publisher": "Journal of movement disorders",
+ "issn": "2005-940X",
+ "date": "2010-10-30",
+ "abstract": "Huntington disease is a neurodegenerative disorder distinguished by the triad of dominant inheritance, choreoathetosis and dementia, usually with onset in the fourth and fifth decades. It is caused by an unstable cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the gene IT15 in locus 4p16.3. Juvenile HD that constitutes about 3% to 10% of all patients is clinically different from adult-onset form and characterized by a larger number of CAG repeats typically exceeding 60. We report a case of a 6-year-old boy with myoclonic seizure and 140 CAG repeats confirmed by molecular genetic analysis.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25316307"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24868381"
},
{
- "id": "pmid:25300330",
+ "id": "pmid:20688164",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25300330",
- "title": "Huntingtin Supplies a csaA-Independent Function Essential for EDTA-Resistant Homotypic Cell Adhesion in Dictyostelium discoideum.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/20688164",
+ "title": "Cerebral cortex structure in prodromal Huntington disease.",
"type": "article-journal",
- "doi": "10.3233/jhd-140112",
- "authors": [
- ["Morgan N", "Thompson"],
- ["Marcy E", "MacDonald"],
- ["James F", "Gusella"],
- ["Michael A", "Myre"]
+ "doi": "10.1016/j.nbd.2010.07.014",
+ "authors": [
+ ["Peggy C", "Nopoulos"],
+ ["Elizabeth H", "Aylward"],
+ ["Christopher A", "Ross"],
+ ["Hans J", "Johnson"],
+ ["Vincent A", "Magnotta"],
+ ["Andrew R", "Juhl"],
+ ["Ronald K", "Pierson"],
+ ["James", "Mills"],
+ ["Douglas R", "Langbehn"],
+ ["Jane S", "Paulsen"]
],
- "publisher": "Journal of Huntington's disease",
- "issn": "1879-6400",
- "date": "2014-01-01",
- "abstract": "The CAG triplet repeat expansion mutation in the HTT locus, which results in neurodegeneration in Huntington's disease, elongates a polyglutamine tract in huntingtin, a HEAT/HEAT-like protein that has been highly structurally conserved through evolution. In several organisms, huntingtin is necessary for proper cell-cell adhesion and normal development.",
+ "publisher": "Neurobiology of disease",
+ "issn": "1095-953X",
+ "date": "2010-08-02",
+ "abstract": "Neuroimaging studies of subjects who are gene-expanded for Huntington Disease, but not yet diagnosed (termed prodromal HD), report that the cortex is \"spared,\" despite the decrement in striatal and cerebral white-matter volume. Measurement of whole-cortex volume can mask more subtle, but potentially clinically relevant regional changes in volume, thinning, or surface area. The current study addressed this limitation by evaluating cortical morphology of 523 prodromal HD subjects. Participants included 693 individuals enrolled in the PREDICT-HD protocol. Of these participants, 523 carried the HD gene mutation (prodromal HD group); the remaining 170 were non gene-expanded and served as the comparison group. Based on age and CAG repeat length, gene-expanded subjects were categorized as \"Far from onset,\" \"Midway to onset,\" \"Near onset,\" and \"already diagnosed.\" MRI scans were processed using FreeSurfer. Cortical volume, thickness, and surface area were not significantly different between the Far from onset group and controls. However, beginning in the Midway to onset group, the cortex showed significant volume decrement, affecting most the posterior and superior cerebral regions. This pattern progressed when evaluating the groups further into the disease process. Areas that remained mostly unaffected included ventral and medial regions of the frontal and temporal cortex. Morphologic changes were mostly in thinning as surface area did not substantially change in most regions. Early in the course of HD, the cortex shows changes that are manifest as cortical thinning and are most robust in the posterior and superior regions of the cerebrum.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25300330"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20688164"
},
{
- "id": "pmid:25136821",
+ "id": "pmid:20655708",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25136821",
- "title": "Instability of trinucleotidic repeats during chromatin remodeling in spermatids.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/20655708",
+ "title": "Association of serotonin transporter promoter (5-HTTLPR) and intron 2 (VNTR-2) polymorphisms with treatment response in temporal lobe epilepsy.",
"type": "article-journal",
- "doi": "10.1002/humu.22637",
+ "doi": "10.1016/j.eplepsyres.2010.06.008",
"authors": [
- ["Olivier", "Simard"],
- ["Marie-Chantal", "Gr\u00e9goire"],
- ["M\u00e9lina", "Arguin"],
- ["Marc-Andr\u00e9", "Brazeau"],
- ["Fr\u00e9d\u00e9ric", "Leduc"],
- ["Isabelle", "Marois"],
- ["Martin V", "Richter"],
- ["Guylain", "Boissonneault"]
+ ["Hrvoje", "Hecimovic"],
+ ["Jasminka", "Stefulj"],
+ ["Lipa", "Cicin-Sain"],
+ ["Vida", "Demarin"],
+ ["Branimir", "Jernej"]
],
- "publisher": "Human mutation",
- "issn": "1098-1004",
- "date": "2014-09-17",
- "abstract": "Transient DNA breaks and evidence of DNA damage response have recently been reported during the chromatin remodeling process in haploid spermatids, creating a potential window of enhanced genetic instability. We used flow cytometry to achieve separation of differentiating spermatids into four highly purified populations using transgenic mice harboring 160 CAG repeats within exon 1 of the human Huntington disease gene (HTT). Trinucleotic repeat expansion was found to occur immediately following the chromatin remodeling steps, confirming the genetic instability of the process and pointing to the origin of paternal anticipation observed in some trinucleotidic repeats diseases.",
+ "publisher": "Epilepsy research",
+ "issn": "1872-6844",
+ "date": "2010-07-23",
+ "abstract": "Temporal lobe epilepsy (TLE) is the most common epilepsy and about 30% of patients have poorly controlled seizures. Neurobiology underlying responsiveness to medical treatment in TLE patients is unclear and there are currently no biological tests to predict course of the disease. Animal and human studies repeatedly suggested serotonergic dysfunction in subjects with TLE. We investigated association of serotonin transporter (5-HTT) gene polymorphisms with medical treatment response in patients with TLE.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25136821"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20655708"
},
{
- "id": "pmid:25101541",
+ "id": "pmid:20645403",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25101541",
- "title": "Ethological endophenotypes are altered by elevated stress hormone levels in both Huntington's disease and wildtype mice.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/20645403",
+ "title": "Tongue force analysis assesses motor phenotype in premanifest and symptomatic Huntington's disease.",
"type": "article-journal",
- "doi": "10.1016/j.bbr.2014.07.044",
+ "doi": "10.1002/mds.23243",
"authors": [
- ["Christina", "Mo"],
- ["Thibault", "Renoir"],
- ["Anthony J", "Hannan"]
+ ["Ralf", "Reilmann"],
+ ["Stefan", "Bohlen"],
+ ["Thomas", "Klopstock"],
+ ["Andreas", "Bender"],
+ ["Adolf", "Weindl"],
+ ["Philipp", "Saemann"],
+ ["Dorothee P", "Auer"],
+ ["E Bernd", "Ringelstein"],
+ ["Herwig W", "Lange"]
],
- "publisher": "Behavioural brain research",
- "issn": "1872-7549",
- "date": "2014-08-04",
- "abstract": "Huntington's disease (HD) is an autosomal dominant, neurodegenerative disorder with cognitive, psychiatric, motor, neuroendocrine and peripheral dysfunctions. Symptom onset and progression can be closely modeled in HD transgenic mice, which facilitate the search for therapeutics and environmental modulators. In the first investigation of chronic stress in HD, we have previously shown that administering a moderate dose of the stress hormone, corticosterone (CORT) had no effect on short-term memory in wildtype (WT) mice but accelerated the onset of the impairment in male R6/1 HD mice. We now extend this investigation to ethological dysfunctions in HD, which we hypothesized to be more susceptible to CORT treatment compared to the same functions in WT littermates. Both genotypes consumed similar doses of CORT dissolved in drinking water across 6-14 weeks of age and were assessed for olfactory sensitivity, nest-building, saccharin preference as well as vocal responses to sociosexual stimuli. In female HD and WT mice, olfactory sensitivity and saccharin preference were reduced by 2 and 4 weeks of CORT, respectively. In males, there was no effect of CORT on saccharin preference, however the number of vocalizations to a female mouse was transiently increased by CORT-drinking, regardless of genotype. Nest-building was severely impaired in HD mice at an early age, but was unaffected by CORT. Our results suggest that the presence of the HD mutation had no bearing on CORT-induced effects at this dose, suggesting that even moderately elevated stress hormone levels can impair ethological behaviors in both the HD and healthy brain.",
+ "publisher": "Movement disorders : official journal of the Movement Disorder Society",
+ "issn": "1531-8257",
+ "date": "2010-10-15",
+ "abstract": "Motor symptoms in Huntington's Disease (HD) are commonly assessed by the Unified Huntington's Disease Rating Scale-Total Motor Score (UHDRS-TMS). However, the UHDRS-TMS is limited by interrater variability, its categorical nature, and insensitivity in premanifest subjects. More objective and quantitative measures of motor phenotype may complement the use of the UHDRS-TMS as outcome measure and increase the power and sensitivity of clinical trials. Deficits in tongue protrusion are well acknowledged in HD and constitute a subitem of the UHDRS-TMS. We, therefore, investigated whether objective and quantitative assessment of tongue protrusion forces (TPF) provides measures that (1) correlate to the severity of motor phenotype detected in the UHDRS-TMS in symptomatic HD, (2) detect a motor phenotype in premanifest HD gene-carriers, and (3) exhibit a correlation to the genotype as assessed by a disease burden score (based on CAG-repeat length and age). Using a precalibrated force transducer, the ability of premanifest gene carriers (n = 15) and subjects with symptomatic HD (n = 20) to generate and maintain isometric TPF at three target force levels (0.25, 0.5, and 1.0 N) was assessed and compared with age-matched controls (n = 20) in a cross-sectional study. Measures of variability of TPF and tongue contact time distinguished controls, premanifest, and symptomatic HD groups and correlated to the UHDRS-TMS and disease burden score, suggesting a strong genotype-phenotype correlation. Group distinction was most reliable at the lowest target force level. We conclude that assessment of TPF may be a useful objective and quantitative marker of motor dysfunction in premanifest and symptomatic HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25101541"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20645403"
},
{
- "id": "pmid:25088714",
+ "id": "pmid:20552561",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25088714",
- "title": "Effects of chronic stress on the onset and progression of Huntington's disease in transgenic mice.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/20552561",
+ "title": "Synthesis of pathological and nonpathological human exon 1 huntingtin.",
"type": "article-journal",
- "doi": "10.1016/j.nbd.2014.07.008",
+ "doi": "10.1002/psc.1252",
"authors": [
- ["Christina", "Mo"],
- ["Thibault", "Renoir"],
- ["Anthony J", "Hannan"]
+ ["David", "Singer"],
+ ["Thomas", "Zauner"],
+ ["Maika", "Genz"],
+ ["Ralf", "Hoffmann"],
+ ["Thole", "Zuchner"]
],
- "publisher": "Neurobiology of disease",
- "issn": "1095-953X",
- "date": "2014-08-01",
- "abstract": "Huntington's disease (HD) is a neurodegenerative disease caused by a tandem repeat mutation encoding an expanded polyglutamine tract. Our previous work showed that memory deficits in HD transgenic mice could be accelerated by increased levels of stress hormone, while memory in WT mice remained unaffected. HD patients experience higher levels of stress compared to the general population and symptoms of HD also include motor, cognitive, psychiatric, sexual and olfactory abnormalities, and an associated decline in activities of daily living. Therefore we investigated the impact of a robust stressor (i.e. restraint) on the onset and progression of a range of behavioral phenotypes in R6/1 transgenic HD mice. Restraint was administered for 1h daily from 6weeks of age and continued until R6/1 mice were clearly motor symptomatic at 14weeks of age. Serum corticosterone levels in both R6/1 and WT littermates were elevated immediately after the last restraint session and weight gain was suppressed in restrained animals throughout the treatment period. Motor coordination and locomotor activity were enhanced by chronic restraint in males, regardless of genotype. However, there was no effect of restraint on motor performances in female animals. At 8weeks of age, olfactory sensitivity was impaired by restraint in R6/1 HD female mice, but not in WT mice. In male R6/1 mice, the olfactory deficit was exacerbated by restraint and olfaction was also impaired in male WT mice. The development of deficits in saccharin preference, Y-maze memory, nest-building and sexually-motivated vocalizations was unaffected by chronic restraint in R6/1 and had little impact on such behavioral performances in WT animals. We provide evidence that chronic stress can negatively modulate specific endophenotypes in HD mice, while the same functions were affected to a lesser extent in WT mice. This vulnerability in HD animals seems to be sex-specific depending on the stress paradigm used. It is hoped that our work will stimulate clinical investigations into the effects of stress on both pre-symptomatic and symptomatic gene-positive members of HD families, and inform the development of new therapeutic approaches.",
+ "publisher": "Journal of peptide science : an official publication of the European Peptide Society",
+ "issn": "1099-1387",
+ "date": "2010-07-01",
+ "abstract": "Huntington's disease (HD) is a neurodegenerative disorder that affects approximately 1 in 10 000 individuals. The underlying gene mutation was identified as a CAG-triplet repeat expansion in the gene huntingtin. The CAG sequence codes for glutamine, and in HD, an expansion of the polyglutamine (poly-Q) stretch above 35 glutamine residues results in pathogenicity. It has been demonstrated in various animal models that only the expression of exon 1 huntingtin, a 67-amino acid-long polypeptide plus a variable poly-Q stretch, is sufficient to cause full HD-like pathology. Therefore, a deeper understanding of exon 1 huntingtin, its structure, aggregation mechanism and interaction with other proteins is crucial for a better understanding of the disease. Here, we describe the synthesis of a 109-amino acid-long exon 1 huntingtin peptide including a poly-Q stretch of 42 glutamines. This microwave-assisted solid phase peptide synthesis resulted in milligram amounts of peptide with high purity. We also synthesized a nonpathogenic version of exon 1 huntingtin (90-amino acid long including a poly-Q stretch of 23 glutamine residues) using the same strategy. In circular dichroism spectroscopy, both polypeptides showed weak alpha-helical properties with the longer peptide showing a higher helical degree. These model peptides have great potential for further biomedical analyses, e.g. for large-scale pre-screenings for aggregation inhibitors, further structural analyses as well as protein-protein interaction studies.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25088714"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20552561"
},
{
- "id": "pmid:25035419",
+ "id": "pmid:20457230",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25035419",
- "title": "Phosphorodiamidate morpholino oligomers suppress mutant huntingtin expression and attenuate neurotoxicity.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/20457230",
+ "title": "Longitudinal analysis of the behavioural phenotype in Hdh(CAG)150 Huntington's disease knock-in mice.",
"type": "article-journal",
- "doi": "10.1093/hmg/ddu349",
+ "doi": "10.1016/j.brainresbull.2010.05.004",
"authors": [
- ["Xin", "Sun"],
- ["Leonard O", "Marque"],
- ["Zachary", "Cordner"],
- ["Jennifer L", "Pruitt"],
- ["Manik", "Bhat"],
- ["Pan P", "Li"],
- ["Geetha", "Kannan"],
- ["Ellen E", "Ladenheim"],
- ["Timothy H", "Moran"],
- ["Russell L", "Margolis"],
- ["Dobrila D", "Rudnicki"]
+ ["Simon", "Brooks"],
+ ["Gemma", "Higgs"],
+ ["Lesley", "Jones"],
+ ["Stephen B", "Dunnett"]
],
- "publisher": "Human molecular genetics",
- "issn": "1460-2083",
- "date": "2014-07-04",
- "abstract": "Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin (HTT) gene. Disease pathogenesis derives, at least in part, from the long polyglutamine tract encoded by mutant HTT. Therefore, considerable effort has been dedicated to the development of therapeutic strategies that significantly reduce the expression of the mutant HTT protein. Antisense oligonucleotides (ASOs) targeted to the CAG repeat region of HTT transcripts have been of particular interest due to their potential capacity to discriminate between normal and mutant HTT transcripts. Here, we focus on phosphorodiamidate morpholino oligomers (PMOs), ASOs that are especially stable, highly soluble and non-toxic. We designed three PMOs to selectively target expanded CAG repeat tracts (CTG22, CTG25 and CTG28), and two PMOs to selectively target sequences flanking the HTT CAG repeat (HTTex1a and HTTex1b). In HD patient-derived fibroblasts with expanded alleles containing 44, 77 or 109 CAG repeats, HTTex1a and HTTex1b were effective in suppressing the expression of mutant and non-mutant transcripts. CTGn PMOs also suppressed HTT expression, with the extent of suppression and the specificity for mutant transcripts dependent on the length of the targeted CAG repeat and on the CTG repeat length and concentration of the PMO. PMO CTG25 reduced HTT-induced cytotoxicity in vitro and suppressed mutant HTT expression in vivo in the N171-82Q transgenic mouse model. Finally, CTG28 reduced mutant HTT expression and improved the phenotype of Hdh(Q7/Q150) knock-in HD mice. These data demonstrate the potential of PMOs as an approach to suppressing the expression of mutant HTT.",
+ "publisher": "Brain research bulletin",
+ "issn": "1873-2747",
+ "date": "2010-05-08",
+ "abstract": "In people with Huntington's disease, an expanded CAG repeat sequence on the HTT gene confers a toxic gain function resulting in a progressive and fatal neurodegeneration. The Hdh((CAG)Q150) Huntington's disease mouse line is a knock-in model of the disease that carries \u223c150 CAG repeats on the normal mouse Htt locus. To determine that these mice are a useful model of the disease, they were assessed longitudinally for motor and cognitive deficits relevant to the human disease state. Each test was conducted bi-monthly across the lifespan of the animal. The results indicate that the Hdh(Q150/Q150) mice were impaired on each of the measures used, with deficits appearing on a 3-stage water maze test at 4 months of age and on prepulse inhibition at 6 months of age, both of which were prior to the manifestation of motor abnormalities. Grip strength, as measured by the inverted cage lid test, was reduced in the Hdh(Q150/Q150) mice from 10 months of age, when the male mice also exhibited weight loss relative to their wildtype littermates. On the accelerating rotarod, deficits in the carrier mice did not appear until they were 21 months old. Our results demonstrate that the Hdh((CAG)150) is a valid model of HD that displays early and progressive cognitive deficits that precede the onset of motor abnormalities.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25035419"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20457230"
},
{
- "id": "pmid:25026978",
+ "id": "pmid:20385209",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25026978",
- "title": "A clinical classification acknowledging neuropsychiatric and cognitive impairment in Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/20385209",
+ "title": "Striatal and white matter predictors of estimated diagnosis for Huntington disease.",
"type": "article-journal",
- "doi": "10.1186/s13023-014-0114-8",
+ "doi": "10.1016/j.brainresbull.2010.04.003",
"authors": [
- ["Tua", "Vinther-Jensen"],
- ["Ida U", "Larsen"],
- ["Lena E", "Hjermind"],
- ["Esben", "Budtz-J\u00f8rgensen"],
- ["Troels T", "Nielsen"],
- ["Anne", "N\u00f8rrem\u00f8lle"],
- ["J\u00f8rgen E", "Nielsen"],
- ["Asmus", "Vogel"]
+ ["Jane S", "Paulsen"],
+ ["Peggy C", "Nopoulos"],
+ ["Elizabeth", "Aylward"],
+ ["Christopher A", "Ross"],
+ ["Hans", "Johnson"],
+ ["Vincent A", "Magnotta"],
+ ["Andrew", "Juhl"],
+ ["Ronald K", "Pierson"],
+ ["James", "Mills"],
+ ["Douglas", "Langbehn"],
+ ["Martha", "Nance"]
],
- "publisher": "Orphanet journal of rare diseases",
- "issn": "1750-1172",
- "date": "2014-07-17",
- "abstract": "Involuntary movements, neuropsychiatric symptoms, and cognitive impairment are all part of the symptom triad in Huntington's disease (HD). Despite the fact that neuropsychiatric symptoms and cognitive decline may be early manifestations of HD, the clinical diagnosis is conventionally based on the presence of involuntary movements and a positive genetic test for the HD CAG repeat expansion. After investigating the frequencies of the triad manifestations in a large outpatient clinical cohort of HD gene-expansion carriers, we propose a new clinical classification.",
+ "publisher": "Brain research bulletin",
+ "issn": "1873-2747",
+ "date": "2010-04-10",
+ "abstract": "Previous MRI studies with participants prior to manifest Huntington disease have been conducted in small single-site samples. The current study reports data from a systematic multi-national study during the prodromal period of Huntington disease and examines whether various brain structures make unique predictions about the proximity to manifest disease. MRI scans were acquired from 657 participants enrolled at 1 of 32 PREDICT-HD research sites. Only prodromal Huntington disease participants (those not meeting motor criteria for diagnosis) were included and subgrouped by estimated diagnosis proximity (Near, Mid, and Far) based upon a formula incorporating age and CAG-repeat length. Results show volumes of all three subgroups differed significantly from Controls for total brain tissue, cerebral spinal fluid, white matter, cortical gray matter, thalamus, caudate, and putamen. Total striatal volume demonstrated the largest differences between Controls and all three prodromal subgroups. Cerebral white matter offered additional independent power in the prediction of estimated proximity to diagnosis. In conclusion, this large cross-sectional study shows that changes in brain volume are detectable years to decades prior to estimated motor diagnosis of Huntington disease. This suggests that a clinical trial of a putative neuroprotective agent could begin as much as 15 years prior to estimated motor diagnosis in a cohort of persons at risk for but not meeting clinical motor diagnostic criteria for Huntington disease, and that neuroimaging (striatal and white matter volumes) may be among the best predictors of diagnosis proximity.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25026978"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20385209"
},
{
- "id": "pmid:24938402",
+ "id": "pmid:20145031",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/24938402",
- "title": "Impaired brain energy metabolism in the BACHD mouse model of Huntington's disease: critical role of astrocyte-neuron interactions.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/20145031",
+ "title": "Late-onset Huntington disease with intermediate CAG repeats: true or false?",
"type": "article-journal",
- "doi": "10.1038/jcbfm.2014.110",
+ "doi": "10.1136/jnnp.2008.170902",
"authors": [
- ["Lydie", "Boussicault"],
- ["Anne-Sophie", "H\u00e9rard"],
- ["Noel", "Calingasan"],
- ["Fanny", "Petit"],
- ["Carole", "Malgorn"],
- ["Nicolas", "Merienne"],
- ["Caroline", "Jan"],
- ["Marie-Claude", "Gaillard"],
- ["Rodrigo", "Lerchundi"],
- ["Luis F", "Barros"],
- ["Carole", "Escartin"],
- ["Thierry", "Delzescaux"],
- ["Jean", "Mariani"],
- ["Philippe", "Hantraye"],
- ["M Flint", "Beal"],
- ["Emmanuel", "Brouillet"],
- ["C\u00e9line", "V\u00e9ga"],
- ["Gilles", "Bonvento"]
+ ["Justus L", "Groen"],
+ ["Rob M A", "de Bie"],
+ ["Elisabeth M J", "Foncke"],
+ ["Raymund A C", "Roos"],
+ ["Klaus L", "Leenders"],
+ ["Marina A J", "Tijssen"]
],
- "publisher": "Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism",
- "issn": "1559-7016",
- "date": "2014-06-18",
- "abstract": "Huntington's disease (HD) is caused by cytosine-adenine-guanine (CAG) repeat expansions in the huntingtin (Htt) gene. Although early energy metabolic alterations in HD are likely to contribute to later neurodegenerative processes, the cellular and molecular mechanisms responsible for these metabolic alterations are not well characterized. Using the BACHD mice that express the full-length mutant huntingtin (mHtt) protein with 97 glutamine repeats, we first demonstrated localized in vivo changes in brain glucose use reminiscent of what is observed in premanifest HD carriers. Using biochemical, molecular, and functional analyses on different primary cell culture models from BACHD mice, we observed that mHtt does not directly affect metabolic activity in a cell autonomous manner. However, coculture of neurons with astrocytes from wild-type or BACHD mice identified mutant astrocytes as a source of adverse non-cell autonomous effects on neuron energy metabolism possibly by increasing oxidative stress. These results suggest that astrocyte-to-neuron signaling is involved in early energy metabolic alterations in HD.",
+ "publisher": "Journal of neurology, neurosurgery, and psychiatry",
+ "issn": "1468-330X",
+ "date": "2010-02-01",
+ "abstract": "Huntington disease (HD) is a neurodegenerative disorder associated with an expanded CAG trinucleotide repeat length in the huntingtin gene. 'Intermediate alleles' with 27 to 35 CAG repeats generally do not cause HD but are unstable upon germ-line transmission. Insights in CAG repeat mosaicism and enhanced trinucleotide expansion in postmitotic neurons indicate that in the intermediate range, other factors than the CAG repeat length in diagnostic tests have to be considered. Here, we report two patients with mild, late onset HD and an intermediate repeat allele. The authors anticipate that intermediate repeats can cause late-onset HD due to disease modifiers and may be more common than previously stated.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24938402"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20145031"
},
{
- "id": "pmid:24841383",
+ "id": "pmid:20001119",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/24841383",
- "title": "Activation of IGF-1 and insulin signaling pathways ameliorate mitochondrial function and energy metabolism in Huntington's Disease human lymphoblasts.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/20001119",
+ "title": "Disrupted temporal control in the R6/2 mouse model of Huntington's disease.",
"type": "article-journal",
- "doi": "10.1007/s12035-014-8735-4",
+ "doi": "10.1037/a0017650",
"authors": [
- ["Luana", "Naia"],
- ["I Lu\u00edsa", "Ferreira"],
- ["Teresa", "Cunha-Oliveira"],
- ["Ana I", "Duarte"],
- ["M\u00e1rcio", "Ribeiro"],
- ["Tatiana R", "Rosenstock"],
- ["M\u00e1rio N", "La\u00e7o"],
- ["Maria J", "Ribeiro"],
- ["Catarina R", "Oliveira"],
- ["Fr\u00e9d\u00e9ric", "Saudou"],
- ["Sandrine", "Humbert"],
- ["A Cristina", "Rego"]
+ ["Fuat", "Balci"],
+ ["Mark", "Day"],
+ ["Aislinn", "Rooney"],
+ ["Dani", "Brunner"]
],
- "publisher": "Molecular neurobiology",
- "issn": "1559-1182",
- "date": "2014-05-20",
- "abstract": "Huntington's disease (HD) is an inherited neurodegenerative disease caused by a polyglutamine repeat expansion in the huntingtin protein. Mitochondrial dysfunction associated with energy failure plays an important role in this untreated pathology. In the present work, we used lymphoblasts obtained from HD patients or unaffected parentally related individuals to study the protective role of insulin-like growth factor 1 (IGF-1) versus insulin (at low nM) on signaling and metabolic and mitochondrial functions. Deregulation of intracellular signaling pathways linked to activation of insulin and IGF-1 receptors (IR,IGF-1R), Akt, and ERK was largely restored by IGF-1 and, at a less extent, by insulin in HD human lymphoblasts. Importantly, both neurotrophic factors stimulated huntingtin phosphorylation at Ser421 in HD cells. IGF-1 and insulin also rescued energy levels in HD peripheral cells, as evaluated by increased ATP and phosphocreatine, and decreased lactate levels. Moreover, IGF-1 effectively ameliorated O2 consumption and mitochondrial membrane potential (\u0394\u03c8m) in HD lymphoblasts, which occurred concomitantly with increased levels of cytochrome c. Indeed, constitutive phosphorylation of huntingtin was able to restore the \u0394\u03c8m in lymphoblasts expressing an abnormal expansion of polyglutamines. HD lymphoblasts further exhibited increased intracellular Ca(2+) levels before and after exposure to hydrogen peroxide (H2O2), and decreased mitochondrial Ca(2+) accumulation, being the later recovered by IGF-1 and insulin in HD lymphoblasts pre-exposed to H2O2. In summary, the data support an important role for IR/IGF-1R mediated activation of signaling pathways and improved mitochondrial and metabolic function in HD human lymphoblasts.",
+ "publisher": "Behavioral neuroscience",
+ "issn": "1939-0084",
+ "date": "2009-12-01",
+ "abstract": "Huntington's disease is characterized by corticostriatal dysfunction and degeneration of the striatum with progressive loss of the medium spiny neurons. These circuits are important for instrumental responding, interval timing, and temporal control over motor output. We investigated the acquisition of timed operant responding in two R6/2 Huntington's Disease models, differing in CAG repeat length and genetic background (115 and 250 CAG repeats, and a mixed CBAxC57 or pure C57 background) and their corresponding wild type controls using the peak procedure. Both mouse lines exhibited similar response control deficits. In unreinforced peak trials, mice either did not learn to terminate an ongoing response past reinforcement time or required more trials to acquisition compared to the wild type mice. While transgenic and wild type mice did not exhibit differences in temporal accuracy, response curves were flatter in transgenic mice, suggesting decreased temporal control over operant responding. The results are discussed in terms of the neurobiology of interval timing, instrumental responding, and the neuropathology of HD and R6/2 mice.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24841383"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20001119"
},
{
- "id": "pmid:24825316",
+ "id": "pmid:19997493",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/24825316",
- "title": "High stress hormone levels accelerate the onset of memory deficits in male Huntington's disease mice.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19997493",
+ "title": "Stoichiometry of base excision repair proteins correlates with increased somatic CAG instability in striatum over cerebellum in Huntington's disease transgenic mice.",
"type": "article-journal",
- "doi": "10.1016/j.nbd.2014.05.004",
+ "doi": "10.1371/journal.pgen.1000749",
"authors": [
- ["Christina", "Mo"],
- ["Terence Y", "Pang"],
- ["Mark I", "Ransome"],
- ["Rachel A", "Hill"],
- ["Thibault", "Renoir"],
- ["Anthony J", "Hannan"]
+ ["Agathi-Vassiliki", "Goula"],
+ ["Brian R", "Berquist"],
+ ["David M", "Wilson"],
+ ["Vanessa C", "Wheeler"],
+ ["Yvon", "Trottier"],
+ ["Karine", "Merienne"]
],
- "publisher": "Neurobiology of disease",
- "issn": "1095-953X",
- "date": "2014-05-10",
- "abstract": "Huntington's disease (HD) is a neurodegenerative disorder caused by a tandem repeat mutation in the huntingtin gene. Lifestyle factors, such as lack of activity may contribute to the variability in the age of disease onset. Therefore, better understanding of environmental modifiers may uncover potential therapeutic approaches to delay disease onset and progression. Recent data suggest that HD patients and transgenic mouse models show a dysregulated stress response. In this present study, we elevated stress hormone levels through oral corticosterone (CORT) treatment and assessed its impact on the development of motor impairment and cognitive deficits using the R6/1 transgenic mouse model of HD. We found that CORT consumption did not alter rotarod performance of R6/1 HD or wild-type (WT) littermates. However, the onset of hippocampal-dependent Y-maze deficits was accelerated in male R6/1 mice by 5days of CORT treatment, whereas short term memory of WT and female R6/1 mice was unaffected. We then further investigated the male HD susceptibility to CORT by measuring TrkB activation, BDNF and glucocorticoid receptor expression as well as the level of cell proliferation in the hippocampus. CORT treatment increased the levels of phosphorylated TrkB in male R6/1 mice only. There were no effects of CORT on hippocampal BDNF protein or mRNA levels; nor on expression of the glucocorticoid receptors in any group. Hippocampal cell proliferation was decreased in male R6/1 mice and this was further reduced in CORT-drinking male R6/1 mice. Female mice (WT and R6/1) appeared to be protected from the impacts of CORT treatment in all our hippocampal measures. Overall, our data demonstrate that treatment with corticosterone is able to modulate the onset of HD symptomatology. We present the first evidence of a male-specific vulnerability to stress impacting on the development of short-term memory deficits in HD. More generally, we found that female mice were protected from the detrimental effects of CORT treatment on a variety of hippocampus-based measures. Hippocampal plasticity and memory in HD may be more susceptible to the impacts of stress in a sex-dependent manner. We propose clinical investigations of stress as a key environmental modifier of HD symptom onset.",
+ "publisher": "PLoS genetics",
+ "issn": "1553-7404",
+ "date": "2009-12-04",
+ "abstract": "Huntington's disease (HD) is a progressive neurodegenerative disorder caused by expansion of an unstable CAG repeat in the coding sequence of the Huntingtin (HTT) gene. Instability affects both germline and somatic cells. Somatic instability increases with age and is tissue-specific. In particular, the CAG repeat sequence in the striatum, the brain region that preferentially degenerates in HD, is highly unstable, whereas it is rather stable in the disease-spared cerebellum. The mechanisms underlying the age-dependence and tissue-specificity of somatic CAG instability remain obscure. Recent studies have suggested that DNA oxidation and OGG1, a glycosylase involved in the repair of 8-oxoguanine lesions, contribute to this process. We show that in HD mice oxidative DNA damage abnormally accumulates at CAG repeats in a length-dependent, but age- and tissue-independent manner, indicating that oxidative DNA damage alone is not sufficient to trigger somatic instability. Protein levels and activities of major base excision repair (BER) enzymes were compared between striatum and cerebellum of HD mice. Strikingly, 5'-flap endonuclease activity was much lower in the striatum than in the cerebellum of HD mice. Accordingly, Flap Endonuclease-1 (FEN1), the main enzyme responsible for 5'-flap endonuclease activity, and the BER cofactor HMGB1, both of which participate in long-patch BER (LP-BER), were also significantly lower in the striatum compared to the cerebellum. Finally, chromatin immunoprecipitation experiments revealed that POLbeta was specifically enriched at CAG expansions in the striatum, but not in the cerebellum of HD mice. These in vivo data fit a model in which POLbeta strand displacement activity during LP-BER promotes the formation of stable 5'-flap structures at CAG repeats representing pre-expanded intermediate structures, which are not efficiently removed when FEN1 activity is constitutively low. We propose that the stoichiometry of BER enzymes is one critical factor underlying the tissue selectivity of somatic CAG expansion.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24825316"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19997493"
},
{
- "id": "pmid:24784230",
+ "id": "pmid:19857538",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/24784230",
- "title": "Neuronal targets for reducing mutant huntingtin expression to ameliorate disease in a mouse model of Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19857538",
+ "title": "The hOGG1 Ser326Cys polymorphism and Huntington's disease.",
"type": "article-journal",
- "doi": "10.1038/nm.3514",
+ "doi": "10.1016/j.tox.2009.10.019",
"authors": [
- ["Nan", "Wang"],
- ["Michelle", "Gray"],
- ["Xiao-Hong", "Lu"],
- ["Jeffrey P", "Cantle"],
- ["Sandra M", "Holley"],
- ["Erin", "Greiner"],
- ["Xiaofeng", "Gu"],
- ["Dyna", "Shirasaki"],
- ["Carlos", "Cepeda"],
- ["Yuqing", "Li"],
- ["Hongwei", "Dong"],
- ["Michael S", "Levine"],
- ["X William", "Yang"]
+ ["Fabio", "Copped\u00e8"],
+ ["Francesca", "Migheli"],
+ ["Roberto", "Ceravolo"],
+ ["Elisa", "Bregant"],
+ ["Anna", "Rocchi"],
+ ["Lucia", "Petrozzi"],
+ ["Elisa", "Unti"],
+ ["Renata", "Lonigro"],
+ ["Gabriele", "Siciliano"],
+ ["Lucia", "Migliore"]
],
- "publisher": "Nature medicine",
- "issn": "1546-170X",
- "date": "2014-04-28",
- "abstract": "Huntington's disease (HD) is a fatal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion leading to an elongated polyglutamine stretch in huntingtin. Mutant huntingtin (mHTT) is ubiquitously expressed in all cells but elicits selective cortical and striatal neurodegeneration in HD. The mechanistic basis for such selective neuronal vulnerability remains unclear. A necessary step toward resolving this enigma is to define the cell types in which mHTT expression is causally linked to the disease pathogenesis. Using a conditional transgenic mouse model of HD, in which the mice express full-length human mHTT from a bacterial artificial chromosome transgene (BACHD), we genetically reduced mHTT expression in neuronal populations in the striatum, cortex or both. We show that reduction of cortical mHTT expression in BACHD mice partially improves motor and psychiatric-like behavioral deficits but does not improve neurodegeneration, whereas reduction of mHTT expression in both neuronal populations consistently ameliorates all behavioral deficits and selective brain atrophy in this HD model. Furthermore, whereas reduction of mHTT expression in cortical or striatal neurons partially ameliorates corticostriatal synaptic deficits, further restoration of striatal synaptic function can be achieved by reduction of mHTT expression in both neuronal cell types. Our study demonstrates distinct but interacting roles of cortical and striatal mHTT in HD pathogenesis and suggests that optimal HD therapeutics may require targeting mHTT in both cortical and striatal neurons.",
+ "publisher": "Toxicology",
+ "issn": "1879-3185",
+ "date": "2009-10-24",
+ "abstract": "Increasing evidence supports a role for oxidative DNA damage and impaired DNA repair mechanisms in the pathogenesis of age related neurodegenerative diseases. Within this context there is a current interest in the understanding of the role played by polymorphisms of DNA repair genes in the inter-individual risk to develop neurodegenerative pathologies, as well as in the onset and the progression of disease symptoms. Particularly, somatic CAG repeat expansion of the gene encoding for huntingtin has been observed in tissues of patients affected by Huntington's disease (HD), including blood and brain. Recent evidence suggests that somatic CAG repeat expansion in HD cells might contribute to disease age at onset and is mediated by the DNA repair OGG1 enzyme, during the removal of 8-oxoguanine (8-oxoG) from the DNA. There is also evidence that the expression of hMTH1, which removes 8-oxoG from the nucleotide pool, protects mice from HD-like symptoms, and progenitor striatal cells from the toxic effects of the mutant huntingtin. The hOGG1 Ser326Cys polymorphism results in reduced OGG1 activity and increased 8-oxoG formation. In the present study, performed on blood DNA from 91 HD subjects, we observed that bearers of the mutant Cys326 allele (Ser326Cys+Cys326Cys) tend to have an increased number of CAG repeats of the expanded HD allele (P=0.049); moreover bearers of at least one copy of the mutant Cys326 allele, mainly heterozygous subjects, showed a significant (P=0.041) earlier disease onset than Ser326Ser wild-type individuals, suggesting a possible role of the hOGG1 Ser326Cys polymorphism in HD phenotype.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24784230"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19857538"
},
{
- "id": "pmid:24706734",
+ "id": "pmid:19823894",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/24706734",
- "title": "The Corticospinal Tract in Huntington's Disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19823894",
+ "title": "Magnetization transfer imaging in 'premanifest' Huntington's disease.",
"type": "article-journal",
- "doi": "10.1093/cercor/bhu065",
+ "doi": "10.1007/s00415-009-5339-4",
"authors": [
- ["O", "Phillips"],
- ["F", "Squitieri"],
- ["C", "Sanchez-Castaneda"],
- ["F", "Elifani"],
- ["A", "Griguoli"],
- ["V", "Maglione"],
- ["C", "Caltagirone"],
- ["U", "Sabatini"],
- ["M", "Di Paola"]
+ ["Caroline K", "Jurgens"],
+ ["Reineke", "Bos"],
+ ["Jasper", "Luyendijk"],
+ ["Marie-No\u00eblle W", "Witjes-An\u00e9"],
+ ["Jeroen", "van der Grond"],
+ ["Huub A M", "Middelkoop"],
+ ["Raymund A C", "Roos"]
],
- "publisher": "Cerebral cortex (New York, N.Y. : 1991)",
- "issn": "1460-2199",
- "date": "2014-04-04",
- "abstract": "Huntington's disease (HD) is characterized by progressive motor impairment. Therefore, the connectivity of the corticospinal tract (CST), which is the main white matter (WM) pathway that conducts motor impulses from the primary motor cortex to the spinal cord, merits particular attention. WM abnormalities have already been shown in presymptomatic (Pre-HD) and symptomatic HD subjects using magnetic resonance imaging (MRI). In the present study, we examined CST microstructure using diffusion tensor imaging (DTI)-based tractography in 30-direction DTI data collected from 100 subjects: Pre-HD subjects (n = 25), HD patients (n = 25) and control subjects (n = 50), and T2*-weighted (iron sensitive) imaging. Results show decreased fractional anisotropy (FA) and increased axial (AD), and radial diffusivity (RD) in the bilateral CST of HD patients. Pre-HD subjects had elevated iron in the left CST, regionally localized between the brainstem and thalamus. CAG repeat length in conjunction with age, as well as motor (UHDRS) assessment were correlated with CST FA, AD, and RD both in Pre-HD and HD. In the presymptomatic phase, increased iron in the inferior portion supports the \"dying back\" hypothesis that axonal damage advances in a retrograde fashion. Furthermore, early iron alteration may cause a high level of toxicity, which may contribute to further damage.",
+ "publisher": "Journal of neurology",
+ "issn": "1432-1459",
+ "date": "2009-10-13",
+ "abstract": "To investigate whether magnetization transfer imaging (MTI) is a useful detector of diffuse brain abnormalities in 'premanifest' carriers of the Huntington's disease (HD) gene mutation. Furthermore we examined the relations between MTI, clinical measures and CAG repeat length. Sixteen premanifest carriers of the HD gene without motor manifestation and 14 non-carriers underwent a clinical evaluation and a MRI scan. MTI analysis of whole brain, grey matter and white matter was performed producing magnetization transfer ratio (MTR) histograms. A lower peak height of the grey matter MTR histogram in carriers was significantly associated with more UHDRS motor abnormalities. Furthermore, a lower peak height of the whole brain, grey and white matter was strongly associated with a longer CAG repeat length. MTI measures themselves did not differ significantly between carriers and non-carriers. In premanifest HD mutation carriers, a lower MTR peak height, reflecting worse histological brain composition, was related to subtle motor abnormalities and higher CAG repeat length. Although we could not detect altered MTI characteristics in carriers of the HD gene mutation without clinical manifestations, we did provide evidence that the MTR peak height might reflect genetic and subclinical disease burden and may be of value in monitoring further disease progression and provide insight in clinical heterogeneity.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24706734"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19823894"
},
{
- "id": "pmid:24633813",
+ "id": "pmid:19810823",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/24633813",
- "title": "Mitochondrial membrane fluidity is consistently increased in different models of Huntington disease: restorative effects of olesoxime.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19810823",
+ "title": "Presymptomatic diagnosis in Huntington's disease: the Mexican experience.",
"type": "article-journal",
- "doi": "10.1007/s12035-014-8663-3",
+ "doi": "10.1089/gtmb.2009.0032",
"authors": [
- ["Janett", "Eckmann"],
- ["Laura E", "Clemens"],
- ["Schamim H", "Eckert"],
- ["Stephanie", "Hagl"],
- ["Libo", "Yu-Taeger"],
- ["Thierry", "Bordet"],
- ["Rebecca M", "Pruss"],
- ["Walter E", "Muller"],
- ["Kristina", "Leuner"],
- ["Huu P", "Nguyen"],
- ["Gunter P", "Eckert"]
+ ["Maria Elisa", "Alonso"],
+ ["Adriana", "Ochoa"],
+ ["Ana Luisa", "Sosa"],
+ ["Yaneth", "Rodr\u00edguez"],
+ ["Mireya", "Ch\u00e1vez"],
+ ["Catherine", "Boll"],
+ ["Petra", "Yescas"],
+ ["Rosario", "Mac\u00edas"],
+ ["Astrid", "Rasmussen"]
],
- "publisher": "Molecular neurobiology",
- "issn": "1559-1182",
- "date": "2014-03-18",
- "abstract": "Huntington disease (HD) is a fatal neurodegenerative disorder caused by a CAG repeat expansion in exon 1 of the huntingtin gene (HTT). One prominent target of the mutant huntingtin protein (mhtt) is the mitochondrion, affecting its morphology, distribution, and function. Thus, mitochondria have been suggested as potential therapeutic targets for the treatment of HD. Olesoxime, a cholesterol-like compound, promotes motor neuron survival and neurite outgrowth in vitro, and its effects are presumed to occur via a direct interaction with mitochondrial membranes (MMs). We examined the properties of MMs isolated from cell and animal models of HD as well as the effects of olesoxime on MM fluidity and cholesterol levels. MMs isolated from brains of aged Hdh Q111/Q111 knock-in mice showed a significant decrease in 1,6-diphenyl-hexatriene (DPH) anisotropy, which is inversely correlated with membrane fluidity. Similar increases in MM fluidity were observed in striatal STHdh Q111/Q111 cells as well as in MMs isolated from brains of BACHD transgenic rats. Treatment of STHdh cells with olesoxime decreased the fluidity of isolated MMs. Decreased membrane fluidity was also measured in olesoxime-treated MMs isolated from brains of HD knock-in mice. In both models, treatment with olesoxime restored HD-specific changes in MMs. Accordingly, olesoxime significantly counteracted the mhtt-induced increase in MM fluidity of MMs isolated from brains of BACHD rats after 12 months of treatment in vivo, possibly by enhancing MM cholesterol levels. Thus, olesoxime may represent a novel pharmacological tool to treat mitochondrial dysfunction in HD.",
+ "publisher": "Genetic testing and molecular biomarkers",
+ "issn": "1945-0257",
+ "date": "2009-12-01",
+ "abstract": "Huntington's disease (HD) is an autosomal dominant progressive, disabling neurodegenerative disorder, for which there is no effective treatment. Predictive testing (PT) for this illness began in 1986 and by 1993 it became more precise after cloning of the gene and the discovery of a CAG repeat expansion as the underlying cause. The objective of this paper is to illustrate the implementation and results of a PT program in a group of at-risk Mexican individuals with 12 years of follow-up. Our PT program conforms to the guidelines proposed by the International Huntington Association and the HD Working group of the World Federation of Neurology. Seventy-five individuals requested the testing, four of them did not fulfill the inclusion criteria, and five abandoned the program voluntarily before receiving the test results. Therefore, 66 results were delivered to 41 noncarriers and 25 mutation carriers. We did not have any catastrophic event, but 4 individuals with normal results and 11 mutation carriers were depressed. Even if this is a small sample, it is the first report of PT in a Latin-American population in which we have been faced with the same problems referred to in larger series.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24633813"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19810823"
},
{
- "id": "pmid:24465260",
+ "id": "pmid:19621255",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/24465260",
- "title": "CAG-Expansion Haplotype Analysis in a Population with a Low Prevalence of Huntington's Disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19621255",
+ "title": "Preimplantation genetic diagnosis of P450 oxidoreductase deficiency and Huntington Disease using three different molecular approaches simultaneously.",
"type": "article-journal",
- "doi": "10.3988/jcn.2014.10.1.32",
+ "doi": "10.1007/s10815-009-9327-5",
"authors": [
- ["Teeratorn", "Pulkes"],
- ["Chutima", "Papsing"],
- ["Sukanya", "Wattanapokayakit"],
- ["Surakameth", "Mahasirimongkol"]
+ ["Trinitat M", "Alberola"],
+ ["Rosa", "Bautista-Ll\u00e1cer"],
+ ["Esther", "Fern\u00e1ndez"],
+ ["Xavier", "Vendrell"],
+ ["Manuel", "P\u00e9rez-Alonso"]
],
- "publisher": "Journal of clinical neurology (Seoul, Korea)",
- "issn": "1738-6586",
- "date": "2014-01-06",
- "abstract": "The prevalence of Huntington's disease (HD) among East Asians is less than one-tenth of that among Caucasians. Such a low prevalence may be attributable to a lack of carriers of specific predisposing haplogroups associated with the high instability of the Huntingtin gene (HTT). The aim of this study was to evaluate the association between specific HTT haplogroups and the occurrence of HD in a Thai population.",
+ "publisher": "Journal of assisted reproduction and genetics",
+ "issn": "1573-7330",
+ "date": "2009-07-21",
+ "abstract": "Description of the confluence of different molecular techniques to detect three different mutations in one cell. The man carries a 20 base pair insertion in exon 12 of the POR gene (c.1551_1552ins20), and the woman carries a point mutation in exon 8 of the POR gene (c.859G>C) plus a triplet repeat expansion in the HTT gene.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24465260"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19621255"
},
{
- "id": "pmid:24459107",
+ "id": "pmid:19607813",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/24459107",
- "title": "HTT-lowering reverses Huntington's disease immune dysfunction caused by NF\u03baB pathway dysregulation.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19607813",
+ "title": "Polyglutamine expansion in huntingtin increases its insertion into lipid bilayers.",
"type": "article-journal",
- "doi": "10.1093/brain/awt355",
+ "doi": "10.1016/j.bbrc.2009.07.039",
"authors": [
- ["Ulrike", "Tr\u00e4ger"],
- ["Ralph", "Andre"],
- ["Nayana", "Lahiri"],
- ["Anna", "Magnusson-Lind"],
- ["Andreas", "Weiss"],
- ["Stephan", "Grueninger"],
- ["Chris", "McKinnon"],
- ["Eva", "Sirinathsinghji"],
- ["Shira", "Kahlon"],
- ["Edith L", "Pfister"],
- ["Roger", "Moser"],
- ["Holger", "Hummerich"],
- ["Michael", "Antoniou"],
- ["Gillian P", "Bates"],
- ["Ruth", "Luthi-Carter"],
- ["Mark W", "Lowdell"],
- ["Maria", "Bj\u00f6rkqvist"],
- ["Gary R", "Ostroff"],
- ["Neil", "Aronin"],
- ["Sarah J", "Tabrizi"]
+ ["Kimberly B", "Kegel"],
+ ["Vitali", "Schewkunow"],
+ ["Ellen", "Sapp"],
+ ["Nicholas", "Masso"],
+ ["Erich E", "Wanker"],
+ ["Marian", "DiFiglia"],
+ ["Wolfgang H", "Goldmann"]
],
- "publisher": "Brain : a journal of neurology",
- "issn": "1460-2156",
- "date": "2014-01-22",
- "abstract": "Huntington's disease is an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. The peripheral innate immune system contributes to Huntington's disease pathogenesis and has been targeted successfully to modulate disease progression, but mechanistic understanding relating this to mutant huntingtin expression in immune cells has been lacking. Here we demonstrate that human Huntington's disease myeloid cells produce excessive inflammatory cytokines as a result of the cell-intrinsic effects of mutant huntingtin expression. A direct effect of mutant huntingtin on the NF\u03baB pathway, whereby it interacts with IKK\u03b3, leads to increased degradation of I\u03baB and subsequent nuclear translocation of RelA. Transcriptional alterations in intracellular immune signalling pathways are also observed. Using a novel method of small interfering RNA delivery to lower huntingtin expression, we show reversal of disease-associated alterations in cellular function-the first time this has been demonstrated in primary human cells. Glucan-encapsulated small interfering RNA particles were used to lower huntingtin levels in human Huntington's disease monocytes/macrophages, resulting in a reversal of huntingtin-induced elevated cytokine production and transcriptional changes. These findings improve our understanding of the role of innate immunity in neurodegeneration, introduce glucan-encapsulated small interfering RNA particles as tool for studying cellular pathogenesis ex vivo in human cells and raise the prospect of immune cell-directed HTT-lowering as a therapeutic in Huntington's disease.",
+ "publisher": "Biochemical and biophysical research communications",
+ "issn": "1090-2104",
+ "date": "2009-07-14",
+ "abstract": "An expanded polyglutamine (Q) tract (>37Q) in huntingtin (htt) causes Huntington disease. Htt associates with membranes and polyglutamine expansion in htt may alter membrane function in Huntington disease through a mechanism that is not known. Here we used differential scanning calorimetry to examine the effects of polyQ expansion in htt on its insertion into lipid bilayers. We prepared synthetic lipid vesicles composed of phosphatidylcholine and phosphatidylethanolamine and tested interactions of htt amino acids 1-89 with 20Q, 32Q or 53Q with the vesicles. GST-htt1-89 with 53Q inserted into synthetic lipid vesicles significantly more than GST-htt1-89 with 20Q or 32Q. We speculate that by inserting more into cell membranes, mutant huntingtin could increase disorder within the lipid bilayer and thereby disturb cellular membrane function.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24459107"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19607813"
},
{
- "id": "pmid:24452335",
+ "id": "pmid:19595623",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/24452335",
- "title": "Copy-number variation of the neuronal glucose transporter gene SLC2A3 and age of onset in Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19595623",
+ "title": "Huntington's disease-like and ataxia syndromes: identification of a family with a de novo SCA17/TBP mutation.",
"type": "article-journal",
- "doi": "10.1093/hmg/ddu022",
+ "doi": "10.1016/j.parkreldis.2009.06.006",
"authors": [
- ["Angelica", "Vittori"],
- ["Carlo", "Breda"],
- ["Mariaelena", "Repici"],
- ["Michael", "Orth"],
- ["Raymund A C", "Roos"],
- ["Tiago F", "Outeiro"],
- ["Flaviano", "Giorgini"],
- ["Edward J", "Hollox"]
+ ["Sara", "Bech"],
+ ["Thor", "Petersen"],
+ ["Anne", "N\u00f8rrem\u00f8lle"],
+ ["Albert", "Gjedde"],
+ ["Lise", "Ehlers"],
+ ["Hans", "Eiberg"],
+ ["Lena E", "Hjermind"],
+ ["Lis", "Hasholt"],
+ ["Erik", "Lundorf"],
+ ["J\u00f8rgen E", "Nielsen"]
],
- "publisher": "Human molecular genetics",
- "issn": "1460-2083",
- "date": "2014-01-22",
- "abstract": "Huntington's disease (HD) is a devastating neurodegenerative disorder which is inherited in an autosomal dominant manner. HD is caused by a trinucleotide CAG repeat expansion that encodes a polyglutamine stretch in the huntingtin (HTT) protein. Mutant HTT expression leads to a myriad of cellular dysfunctions culminating in neuronal loss and consequent motor, cognitive and psychiatric disturbances in HD patients. The length of the CAG repeat is inversely correlated with age of onset (AO) in HD patients, while environmental and genetic factors can further modulate this parameter. Here, we explored whether the recently described copy-number variation (CNV) of the gene SLC2A3-which encodes the neuronal glucose transporter GLUT3-could modulate AO in HD. Strikingly, we found that increased dosage of SLC2A3 delayed AO in an HD cohort of 987 individuals, and that this correlated with increased levels of GLUT3 in HD patient cells. To our knowledge this is the first time that CNV of a candidate gene has been found to modulate HD pathogenesis. Furthermore, we found that increasing dosage of Glut1-the Drosophila melanogaster homologue of this glucose transporter-ameliorated HD-relevant phenotypes in fruit flies, including neurodegeneration and life expectancy. As alterations in glucose metabolism have been implicated in HD pathogenesis, this study may have important therapeutic relevance for HD.",
+ "publisher": "Parkinsonism & related disorders",
+ "issn": "1873-5126",
+ "date": "2010-01-01",
+ "abstract": "The autosomal dominant spinocerebellar ataxias, commonly referred to as SCAs, are clinically and genetically heterogeneous neurodegenerative disorders. Twenty-eight genetic subtypes have been identified, of which 7 are caused by expansion of a CAG trinucleotide repeat that encodes a polyglutamine tract in the respective proteins. SCA17 is caused by a CAG/CAA repeat expansion in the TATA box-binding protein-gene (TBP). In some cases the clinical phenotype of SCA17 overlaps that of Huntington's disease (HD), hence the use of the term Huntington's disease-like. We screened 89 patients with a Huntington's disease-like phenotype without the HD-gene mutation and 178 patients with genetically unclassified cerebellar ataxia for the mutation in TBP. A 33-year old woman presenting with an HD like phenotype with a de novo 54 CAG/CAA repeat expansion was identified. Her normal allele included 38 repeats. The patient's mother and father both carried normal range repeats, 38/38 and 33/39 respectively. Analysis of the repeat structures revealed that the expansion had occurred upon expansion of the longer paternal allele. We conclude that, however rare, SCA17 must be considered as a cause of Huntington's disease-like phenotypes and ataxia syndromes, also in isolated cases.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24452335"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19595623"
},
{
- "id": "pmid:24390280",
+ "id": "pmid:21048629",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/24390280",
- "title": "Intrajugular vein delivery of AAV9-RNAi prevents neuropathological changes and weight loss in Huntington's disease mice.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21048629",
+ "title": "A survey of (CAG)n repeats causing juvenile Huntington disease in an Iranian family with 4 affected members.",
"type": "article-journal",
- "doi": "10.1038/mt.2013.289",
+ "doi": "",
"authors": [
- ["Brett D", "Dufour"],
- ["Catherine A", "Smith"],
- ["Randall L", "Clark"],
- ["Timothy R", "Walker"],
- ["Jodi L", "McBride"]
+ ["Mehrdokht", "Mazdeh"],
+ ["Hamid", "Pour-Jafari"],
+ ["Ali", "Ghaleiha"],
+ ["Bita", "Pour-Jafari"]
],
- "publisher": "Molecular therapy : the journal of the American Society of Gene Therapy",
- "issn": "1525-0024",
- "date": "2014-01-06",
- "abstract": "Huntington's disease (HD) is a fatal neurological disorder caused by a CAG repeat expansion in the HTT gene, which encodes a mutant huntingtin protein (mHTT). The mutation confers a toxic gain of function on huntingtin, leading to widespread neurodegeneration and inclusion formation in many brain regions. Although the hallmark symptom of HD is hyperkinesia stemming from striatal degeneration, several other brain regions are affected which cause psychiatric, cognitive, and metabolic symptoms. Additionally, mHTT expression in peripheral tissue is associated with skeletal muscle atrophy, cardiac failure, weight loss, and diabetes. We, and others, have demonstrated a prevention of motor symptoms in HD mice following direct striatal injection of adeno-associated viral vector (AAV) serotype 1 encoding an RNA interference (RNAi) construct targeting mutant HTT mRNA (mHTT). Here, we expand these efforts and demonstrate that an intrajugular vein injection of AAV serotype 9 (AAV9) expressing a mutant HTT-specific RNAi construct significantly reduced mHTT expression in multiple brain regions and peripheral tissues affected in HD. Correspondingly, this approach prevented atrophy and inclusion formation in key brain regions as well as the severe weight loss germane to HD transgenic mice. These results demonstrate that systemic delivery of AAV9-RNAi may provide more widespread clinical benefit for patients suffering from HD.",
+ "publisher": "Neurosciences (Riyadh, Saudi Arabia)",
+ "issn": "1319-6138",
+ "date": "2009-07-01",
+ "abstract": "Huntington's disease is caused by a trinucleotide repeat expansion (CAG)n in the gene coding for Huntingtin (Htt) and is one of the several polyglutamine diseases. Its physical symptoms occur in a large range of ages, with a mean occurrence in a person's late 40's and early 50's. Almost all references indicated that if the age of onset is below 20 years then it is known as juvenile HD. Our case was an Iranian family with 4 affected siblings (2 sisters and 2 brothers). In addition to 4 affected children, they had 5 normal male progenies. There was no any other case in their family history. The onset age of the disease in our case family was 20 to 25 years. Their parents were unaffected and nonconsanguineous. Analysis of the pathogenic (CAG)n repeat region of the HD gene for the affected members have showed an expansion allele with 46, 50, 46, and 44 repeats in 4 affected siblings. Our results indicated that the age of 20 years maybe is not a stable limit point for all cases of juvenile HD, and perhaps onset ages are related with the CAG repeat sizes in such individuals.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24390280"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21048629"
},
{
- "id": "pmid:24359926",
+ "id": "pmid:19484127",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/24359926",
- "title": "Nucleotide excision repair and the 26S proteasome function together to promote trinucleotide repeat expansions.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19484127",
+ "title": "Genetic knock-down of HDAC7 does not ameliorate disease pathogenesis in the R6/2 mouse model of Huntington's disease.",
"type": "article-journal",
- "doi": "10.1016/j.dnarep.2013.11.004",
+ "doi": "10.1371/journal.pone.0005747",
"authors": [
- ["Claire", "Concannon"],
- ["Robert S", "Lahue"]
+ ["Caroline L", "Benn"],
+ ["Rachel", "Butler"],
+ ["Lydia", "Mariner"],
+ ["Jude", "Nixon"],
+ ["Hilary", "Moffitt"],
+ ["Michal", "Mielcarek"],
+ ["Ben", "Woodman"],
+ ["Gillian P", "Bates"]
],
- "publisher": "DNA repair",
- "issn": "1568-7856",
- "date": "2013-12-17",
- "abstract": "Trinucleotide repeat (TNR) expansion underpins a number of inheritable neurological human disorders. Multiple mechanisms are thought to contribute to the expansion process. The incorrect processing of the repeat tract by DNA repair proteins can drive this mutation process forward, as expansions are suppressed following ablation of certain repair factors in mouse models and cell models of disease. Nucleotide excision repair (NER) is one repair pathway implicated in TNR instability, although most previous work focussed on TNR contractions, not expansions. Here we investigated the role of NER in modulating expansions of threshold-length (CTG\u00b7CAG) repeats in yeast. We show that both the global genome and transcription-coupled repair subpathways promote expansions of threshold-length TNRs. Furthermore, NER works with the 26S proteasome to drive expansions, based on analysis of double mutants defective in both pathways, and of Rad23, a protein involved in both NER and the shuttling of ubiquitinated proteins to the proteasome. This work provides the first evidence that both subpathways of NER can promote threshold-length TNR expansions and that NER interacts with the proteasome to drive expansions.",
+ "publisher": "PloS one",
+ "issn": "1932-6203",
+ "date": "2009-06-01",
+ "abstract": "Huntington's disease (HD) is an inherited, progressive neurological disorder caused by a CAG/polyglutamine repeat expansion, for which there is no effective disease modifying therapy. In recent years, transcriptional dysregulation has emerged as a pathogenic process that appears early in disease progression. Administration of histone deacetylase (HDAC) inhibitors such as suberoylanilide hydroxamic acid (SAHA) have consistently shown therapeutic potential in models of HD, at least partly through increasing the association of acetylated histones with down-regulated genes and by correcting mRNA abnormalities. The HDAC enzyme through which SAHA mediates its beneficial effects in the R6/2 mouse model of HD is not known. Therefore, we have embarked on a series of genetic studies to uncover the HDAC target that is relevant to therapeutic development for HD. HDAC7 is of interest in this context because SAHA has been shown to decrease HDAC7 expression in cell culture systems in addition to inhibiting enzyme activity. After confirming that expression levels of Hdac7 are decreased in the brains of wild type and R6/2 mice after SAHA administration, we performed a genetic cross to determine whether genetic reduction of Hdac7 would alleviate phenotypes in the R6/2 mice. We found no improvement in a number of physiological or behavioral phenotypes. Similarly, the dysregulated expression levels of a number of genes of interest were not improved suggesting that reduction in Hdac7 does not alleviate the R6/2 HD-related transcriptional dysregulation. Therefore, we conclude that the beneficial effects of HDAC inhibitors are not predominantly mediated through the inhibition of HDAC7.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24359926"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19484127"
},
{
- "id": "pmid:24314096",
+ "id": "pmid:19465745",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/24314096",
- "title": "Clinical and genetic features of Huntington disease in Sri Lanka.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19465745",
+ "title": "Somatic expansion of the Huntington's disease CAG repeat in the brain is associated with an earlier age of disease onset.",
"type": "article-journal",
- "doi": "10.1186/1471-2377-13-191",
+ "doi": "10.1093/hmg/ddp242",
"authors": [
- ["Dulika S", "Sumathipala"],
- ["Rohan W", "Jayasekara"],
- ["Vajira H W", "Dissanayake"]
+ ["Meera", "Swami"],
+ ["Audrey E", "Hendricks"],
+ ["Tammy", "Gillis"],
+ ["Tiffany", "Massood"],
+ ["Jayalakshmi", "Mysore"],
+ ["Richard H", "Myers"],
+ ["Vanessa C", "Wheeler"]
],
- "publisher": "BMC neurology",
- "issn": "1471-2377",
- "date": "2013-12-05",
- "abstract": "Huntington disease was one of the first neurological hereditary diseases for which genetic testing was made possible as early as 1993. The study describes the clinical and genetic characteristics of patients with Huntington disease in Sri Lanka.",
+ "publisher": "Human molecular genetics",
+ "issn": "1460-2083",
+ "date": "2009-05-23",
+ "abstract": "The age of onset of Huntington's disease (HD) is determined primarily by the length of the HD CAG repeat mutation, but is also influenced by other modifying factors. Delineating these modifiers is a critical step towards developing validated therapeutic targets in HD patients. The HD CAG repeat is somatically unstable, undergoing progressive length increases over time, particularly in brain regions that are the targets of neurodegeneration. Here, we have explored the hypothesis that somatic instability of the HD CAG repeat is itself a modifier of disease. Using small-pool PCR, we quantified somatic instability in the cortex region of the brain from a cohort of HD individuals exhibiting phenotypic extremes of young and old disease onset as predicted by the length of their constitutive HD CAG repeat lengths. After accounting for constitutive repeat length, somatic instability was found to be a significant predictor of onset age, with larger repeat length gains associated with earlier disease onset. These data are consistent with the hypothesis that somatic HD CAG repeat length expansions in target tissues contribute to the HD pathogenic process, and support pursuing factors that modify somatic instability as viable therapeutic targets.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24314096"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19465745"
},
{
- "id": "pmid:24286237",
+ "id": "pmid:19250382",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/24286237",
- "title": "Genetic variation in the monoamine oxidase A and serotonin transporter genes in sudden infant death syndrome.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19250382",
+ "title": "4p16.3 haplotype modifying age at onset of Huntington disease.",
"type": "article-journal",
- "doi": "10.1111/apa.12526",
+ "doi": "10.1111/j.1399-0004.2008.01136.x",
"authors": [
- ["Siri H", "Opdal"],
- ["\u00c5shild", "Vege"],
- ["Torleiv O", "Rognum"]
+ ["A", "N\u00f8rrem\u00f8lle"],
+ ["E", "Budtz-J\u00f8rgensen"],
+ ["K", "Fenger"],
+ ["J E", "Nielsen"],
+ ["S A", "S\u00f8rensen"],
+ ["L", "Hasholt"]
],
- "publisher": "Acta paediatrica (Oslo, Norway : 1992)",
- "issn": "1651-2227",
- "date": "2013-12-27",
- "abstract": "The purpose of this study was to investigate common polymorphisms in the genes encoding monoamine oxidase A (MAOA) and serotonin transporter (5-HTT) in Norwegian cases of sudden infant death syndrome (SIDS). This was done to further elucidate the role of genetic variation in these genes and SIDS.",
+ "publisher": "Clinical genetics",
+ "issn": "1399-0004",
+ "date": "2009-03-01",
+ "abstract": "Huntington disease (HD) is caused by an expanded CAG repeat sequence in the HD gene. Although the age at onset is correlated to the CAG repeat length, this correlation only explains approximately half of the variation in onset age. Less variation between siblings indicates that the variation is, in part, explained by genetic modifiers. We analyzed polymorphic loci within or close to the HD gene on the HD chromosome in Danish HD patients. We found one specific haplotype segregating with later age at onset, compared with patients with similar CAG repeat length and another haplotype. The nine Danish families in the study carrying this haplotype most likely have a common founder. Several of the polymorphic loci displayed alleles that may be specific to the late-onset haplotype, implicating that from this study we cannot determine which of the loci tested (or other polymorphic loci in this chromosomal area) do in fact contain genetic modifiers of age at onset.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24286237"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19250382"
},
{
- "id": "pmid:24047873",
+ "id": "pmid:21415933",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/24047873",
- "title": "Modelling and inference reveal nonlinear length-dependent suppression of somatic instability for small disease associated alleles in myotonic dystrophy type 1 and Huntington disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21415933",
+ "title": "Diffusion Tensor Imaging in Preclinical Huntington's Disease.",
"type": "article-journal",
- "doi": "10.1098/rsif.2013.0605",
+ "doi": "10.1007/s11682-008-9051-2",
"authors": [
- ["Catherine F", "Higham"],
- ["Darren G", "Monckton"]
+ ["Vincent A", "Magnotta"],
+ ["Jinsuh", "Kim"],
+ ["Tim", "Koscik"],
+ ["Leigh J", "Beglinger"],
+ ["Daisy", "Espinso"],
+ ["Doug", "Langbehn"],
+ ["Peg", "Nopoulos"],
+ ["Jane S", "Paulsen"]
],
- "publisher": "Journal of the Royal Society, Interface",
- "issn": "1742-5662",
- "date": "2013-09-18",
- "abstract": "More than 20 human genetic diseases are associated with inheriting an unstable expanded DNA simple sequence tandem repeat, for example, CTG (cytosine-thymine-guanine) repeats in myotonic dystrophy type 1 (DM1) and CAG (cytosine-adenine-guanine) repeats in Huntington disease (HD). These sequences mutate by changing the number of repeats not just between generations, but also during the lifetime of affected individuals. Levels of somatic instability contribute to disease onset and progression but as changes are tissue-specific, age- and repeat length-dependent, interpretation of the level of somatic instability in an individual is confounded by these considerations. Mathematical models, fitted to CTG repeat length distributions derived from blood DNA, from a large cohort of DM1-affected or at risk individuals, have recently been used to quantify inherited repeat lengths and mutation rates. Taking into account age, the estimated mutation rates are lower than predicted among individuals with small alleles (inherited repeat lengths less than 100 CTGs), suggesting that these rates may be suppressed at the lower end of the disease-causing range. In this study, we propose that a length-specific effect operates within this range and tested this hypothesis using a model comparison approach. To calibrate the extended model, we used data derived from blood DNA from DM1 individuals and, for the first time, buccal DNA from HD individuals. In a novel application of this extended model, we identified individuals whose effective repeat length, with regards to somatic instability, is less than their actual repeat length. A plausible explanation for this distinction is that the expanded repeat tract is compromised by interruptions or other unusual features. We quantified effective length for a large cohort of DM1 individuals and showed that effective length better predicts age of onset than inherited repeat length, thus improving the genotype-phenotype correlation. Under the extended model, we removed some of the bias in mutation rates making them less length-dependent. Consequently, rates adjusted in this way will be better suited as quantitative traits to investigate cis- or trans-acting modifiers of somatic mosaicism, disease onset and progression.",
+ "publisher": "Brain imaging and behavior",
+ "issn": "1931-7565",
+ "date": "2009-03-01",
+ "abstract": "Diffusion tensor imaging was used to study brain related changes in white matter that may be associated with Huntington's Disease progression. Thirty-one preclinical gene-mutation carriers were imaged cross-sectionally using diffusion tensor and anatomical brain imaging. Subjects were individuals who had a known gene mutation for HD but did not manifest motor diagnostic criteria for HD. Fractional anisotropy scalar maps showed a positive correlation with five year probability of diagnosis (based upon gene repeat length and current age) in the putamen and a negative correlation in the external capsule. This study shows that scalar maps generated from diffusion tensor imaging may be directly related to the earliest stages of disease progression within HD, even before a diagnosis is given. Findings suggest that DTI measures, therefore, may have the ability to act as a biomarker for disease progression in clinical trials of pre-manifest subjects.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24047873"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21415933"
},
{
- "id": "pmid:24041806",
+ "id": "pmid:19200361",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/24041806",
- "title": "Oxidative stress causes DNA triplet expansion in Huntington's disease mouse embryonic stem cells.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19200361",
+ "title": "PGC-1alpha as modifier of onset age in Huntington disease.",
"type": "article-journal",
- "doi": "10.1016/j.scr.2013.08.010",
+ "doi": "10.1186/1750-1326-4-10",
"authors": [
- ["Ida", "Jonson"],
- ["Rune", "Ougland"],
- ["Arne", "Klungland"],
- ["Elisabeth", "Larsen"]
+ ["Elahe", "Taherzadeh-Fard"],
+ ["Carsten", "Saft"],
+ ["J\u00fcrgen", "Andrich"],
+ ["Stefan", "Wieczorek"],
+ ["Larissa", "Arning"]
],
- "publisher": "Stem cell research",
- "issn": "1876-7753",
- "date": "2013-08-27",
- "abstract": "Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded trinucleotide CAG repeat in the Huntingtin (Htt) gene. The molecular basis for the development and progression of HD is currently poorly understood. However, different DNA repair pathways have been implicated in both somatic expansion and disease progression. Embryonic stem cells provide a remarkable in vitro system to study HD and could have implications for understanding disease development and for therapeutic treatment. Here, we derive pluripotent stem cells from the mouse R6/1 HD model and demonstrate that repeated exposure to genotoxic agents inducing oxidative DNA damage gave a significant and dose dependent increase in somatic triplet expansion. Further investigation into specific steps of DNA repair revealed impaired double stranded break repair in exposed R6/1 cells, accompanied by the induction of apoptosis. We also found that differentiation status, and consequently DNA repair efficiency influenced somatic expansion. Our data underscore the importance of DNA damage and repair for the stability of the HD triplet in pluripotent stem cells.",
+ "publisher": "Molecular neurodegeneration",
+ "issn": "1750-1326",
+ "date": "2009-02-06",
+ "abstract": "Although there is a strong correlation between CAG repeat length and age at onset (AO) of motor symptoms, individual Huntington disease (HD) patients may differ dramatically in onset age and disease manifestations despite similar CAG repeat lengths. This has led to a search for genetic factors that influence AO. In order to identify such a genetic modifier, we analysed polymorphisms in the PGC-1alpha gene. Recent data indicate inhibition of PGC-1alpha function by mutant Htt supporting a link between transcriptional deregulation and mitochondrial dysfunction in HD. In > 400 HD patients, a polymorphism located within intron 2, a potential recombination hot spot, explains a small, but statistically significant, amount of the variability in AO. Our data suggest that PGC-1alpha has modifying effects on the pathogenic process in HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24041806"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19200361"
},
{
- "id": "pmid:24027120",
+ "id": "pmid:19193881",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/24027120",
- "title": "Nonparametric modeling and analysis of association between Huntington's disease onset and CAG repeats.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19193881",
+ "title": "Decreased BDNF levels are a major contributor to the embryonic phenotype of huntingtin knockdown zebrafish.",
"type": "article-journal",
- "doi": "10.1002/sim.5971",
+ "doi": "10.1523/jneurosci.6039-08.2009",
"authors": [
- ["Yanyuan", "Ma"],
- ["Yuanjia", "Wang"]
+ ["Heike", "Diekmann"],
+ ["Oleg", "Anichtchik"],
+ ["Angeleen", "Fleming"],
+ ["Marie", "Futter"],
+ ["Paul", "Goldsmith"],
+ ["Alan", "Roach"],
+ ["David C", "Rubinsztein"]
],
- "publisher": "Statistics in medicine",
- "issn": "1097-0258",
- "date": "2013-09-12",
- "abstract": "Huntington's disease (HD) is a neurodegenerative disorder with a dominant genetic mode of inheritance caused by an expansion of CAG repeats on chromosome 4. Typically, a longer sequence of CAG repeat length is associated with increased risk of experiencing earlier onset of HD. Previous studies of the association between HD onset age and CAG length have favored a logistic model, where the CAG repeat length enters the mean and variance components of the logistic model in a complex exponential-linear form. To relax the parametric assumption of the exponential-linear association to the true HD onset distribution, we propose to leave both mean and variance functions of the CAG repeat length unspecified and perform semiparametric estimation in this context through a local kernel and backfitting procedure. Motivated by including family history of HD information available in the family members of participants in the Cooperative Huntington's Observational Research Trial (COHORT), we develop the methodology in the context of mixture data, where some subjects have a positive probability of being risk free. We also allow censoring on the age at onset of disease and accommodate covariates other than the CAG length. We study the theoretical properties of the proposed estimator and derive its asymptotic distribution. Finally, we apply the proposed methods to the COHORT data to estimate the HD onset distribution using a group of study participants and the disease family history information available on their family members.",
+ "publisher": "The Journal of neuroscience : the official journal of the Society for Neuroscience",
+ "issn": "1529-2401",
+ "date": "2009-02-04",
+ "abstract": "Huntington's disease (HD) is an autosomal dominant, neurodegenerative condition caused by a CAG trinucleotide repeat expansion that is translated into an abnormally long polyglutamine tract in the protein huntingtin. Genetic and transgenic studies suggest that the mutation causes disease predominantly via gain-of-function mechanisms. However, loss of normal huntingtin function resulting from the polyglutamine expansion might also contribute to the pathogenesis of HD. Here, we have studied the effects of huntingtin knockdown in zebrafish using morpholino antisense oligonucleotides, as its huntingtin orthologue has 70% amino acid identity with the human protein. Reduced huntingtin levels did not impact on gastrulation and early development, but caused massive apoptosis of neuronal cells by 24 hpf. This was accompanied by impaired neuronal development, resulting in small eyes and heads and enlargement of brain ventricles. Older huntingtin knockdown fish developed lower jaw abnormalities with most branchial arches missing. Molecular analysis revealed that BDNF expression was reduced by approximately 50%. Reduction of BDNF levels by injection of a BDNF morpholino resulted in phenotypes very similar to those seen in huntingtin knockdown zebrafish. The phenotypes of both huntingtin- and BDNF-knockdown zebrafish showed significant rescue when treated with exogenous BDNF protein. This underscores the physiological importance of huntingtin as a regulator of BDNF production and suggests that loss of BDNF is a major cause of the developmental abnormalities seen with huntingtin knockdown in zebrafish. Increasing BDNF expression may represent a useful strategy for Huntington's disease treatment.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24027120"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19193881"
},
{
- "id": "pmid:24000094",
+ "id": "pmid:19133136",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/24000094",
- "title": "Relationship of Mediterranean diet and caloric intake to phenoconversion in Huntington disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19133136",
+ "title": "The gene coding for PGC-1alpha modifies age at onset in Huntington's Disease.",
"type": "article-journal",
- "doi": "10.1001/jamaneurol.2013.3487",
+ "doi": "10.1186/1750-1326-4-3",
"authors": [
- ["Karen", "Marder"],
- ["Yian", "Gu"],
- ["Shirley", "Eberly"],
- ["Caroline M", "Tanner"],
- ["Nikolaos", "Scarmeas"],
- ["David", "Oakes"],
- ["Ira", "Shoulson"]
+ ["Patrick", "Weydt"],
+ ["Selma M", "Soyal"],
+ ["Cinzia", "Gellera"],
+ ["Stefano", "Didonato"],
+ ["Claus", "Weidinger"],
+ ["Hannes", "Oberkofler"],
+ ["G Bernhard", "Landwehrmeyer"],
+ ["Wolfgang", "Patsch"]
],
- "publisher": "JAMA neurology",
- "issn": "2168-6157",
- "date": "2013-11-01",
- "abstract": "Adherence to Mediterranean-type diet (MeDi) may delay onset of Alzheimer and Parkinson diseases. Whether adherence to MeDi affects time to phenoconversion in Huntington disease (HD), a highly penetrant, single-gene disorder, is unknown.",
+ "publisher": "Molecular neurodegeneration",
+ "issn": "1750-1326",
+ "date": "2009-01-08",
+ "abstract": "Huntington's disease (HD) is one of the most common autosomal dominant inherited, neurodegenerative disorders. It is characterized by progressive motor, emotional and cognitive dysfunction. In addition metabolic abnormalities such as wasting and altered energy expenditure are increasingly recognized as clinical hallmarks of the disease. HD is caused by an unstable CAG repeat expansion in the HD gene (HTT), localized on chromosome 4p16.3. The number of CAG repeats in the HD gene is the main predictor of disease-onset, but the remaining variation is strongly heritable. Transcriptional dysregulation, mitochondrial dysfunction and enhanced oxidative stress have been implicated in the pathogenesis. Recent studies suggest that PGC-1alpha, a transcriptional master regulator of mitochondrial biogenesis and metabolism, is defective in HD. A genome wide search for modifier genes of HD age-of-onset had suggested linkage at chromosomal region 4p16-4p15, near the locus of PPARGC1A, the gene coding for PGC-1alpha. We now present data of 2-loci PPARGC1A block 2 haplotypes, showing an effect upon age-at-onset in 447 unrelated HD patients after statistical consideration of CAG repeat lengths in both HTT alleles. Block 1 haplotypes were not associated with the age-at-onset. Homozygosity for the 'protective' block 2 haplotype was associated with a significant delay in disease onset. To our knowledge this is the first study to show clinically relevant effects of the PGC-1alpha system on the course of Huntington's disease in humans.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24000094"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19133136"
},
{
- "id": "pmid:23974869",
+ "id": "pmid:19014073",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23974869",
- "title": "Glutathione peroxidase activity is neuroprotective in models of Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19014073",
+ "title": "Association study of serotonin transporter gene polymorphisms with obstructive sleep apnea syndrome in Chinese Han population.",
"type": "article-journal",
- "doi": "10.1038/ng.2732",
+ "doi": "10.1093/sleep/31.11.1535",
"authors": [
- ["Robert P", "Mason"],
- ["Massimiliano", "Casu"],
- ["Nicola", "Butler"],
- ["Carlo", "Breda"],
- ["Susanna", "Campesan"],
- ["Jannine", "Clapp"],
- ["Edward W", "Green"],
- ["Devyani", "Dhulkhed"],
- ["Charalambos P", "Kyriacou"],
- ["Flaviano", "Giorgini"]
+ ["Weihua", "Yue"],
+ ["Huiguo", "Liu"],
+ ["Jishui", "Zhang"],
+ ["Xianghui", "Zhang"],
+ ["Xiaoping", "Wang"],
+ ["Tieqiao", "Liu"],
+ ["Pozi", "Liu"],
+ ["Wei", "Hao"]
],
- "publisher": "Nature genetics",
- "issn": "1546-1718",
- "date": "2013-08-25",
- "abstract": "Huntington's disease is a fatal neurodegenerative disorder caused by a CAG repeat expansion encoding a polyglutamine tract in the huntingtin (Htt) protein. Here we report a genome-wide overexpression suppressor screen in which we identified 317 ORFs that ameliorate the toxicity of a mutant Htt fragment in yeast and that have roles in diverse cellular processes, including mitochondrial import and copper metabolism. Two of these suppressors encode glutathione peroxidases (GPxs), which are conserved antioxidant enzymes that catalyze the reduction of hydrogen peroxide and lipid hydroperoxides. Using genetic and pharmacological approaches in yeast, mammalian cells and Drosophila, we found that GPx activity robustly ameliorates Huntington's disease-relevant metrics and is more protective than other antioxidant approaches tested here. Notably, we found that GPx activity, unlike many antioxidant treatments, does not inhibit autophagy, which is an important mechanism for clearing mutant Htt. Because previous clinical trials have indicated that GPx mimetics are well tolerated in humans, this study may have important implications for treating Huntington's disease.",
+ "publisher": "Sleep",
+ "issn": "0161-8105",
+ "date": "2008-11-01",
+ "abstract": "Since the serotonin (5-HT) is associated with circadian rhythm and breathing regulation, the serotonin transporter (5-HTT), which plays an important role in serotoninergic transmission, might be a strong candidate gene in the pathogenesis of obstructive sleep apnea syndrome (OSAS).",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23974869"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19014073"
},
{
- "id": "pmid:23946314",
+ "id": "pmid:19012814",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23946314",
- "title": "De novo Huntington disease caused by 26-44 CAG repeat expansion on a low-risk haplotype.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19012814",
+ "title": "Obsessive and compulsive symptoms in prediagnosed Huntington's disease.",
"type": "article-journal",
- "doi": "10.1212/wnl.0b013e3182a4a4af",
+ "doi": "10.4088/jcp.v69n1111",
"authors": [
- ["Gunnar", "Houge"],
- ["Ove", "Bruland"],
- ["Inga", "Bj\u00f8rnevoll"],
- ["Michael R", "Hayden"],
- ["Alicia", "Semaka"]
+ ["Leigh J", "Beglinger"],
+ ["Jane S", "Paulsen"],
+ ["David B", "Watson"],
+ ["Chiachi", "Wang"],
+ ["Kevin", "Duff"],
+ ["Douglas R", "Langbehn"],
+ ["David J", "Moser"],
+ ["Henry L", "Paulson"],
+ ["Elizabeth H", "Aylward"],
+ ["Noelle E", "Carlozzi"],
+ ["Sarah", "Queller"],
+ ["Julie C", "Stout"]
],
- "publisher": "Neurology",
- "issn": "1526-632X",
- "date": "2013-08-14",
- "abstract": "Huntington disease (HD, OMIM #143100) is a dominantly inherited neurodegenerative disorder due to a CAG repeat expansion in the",
+ "publisher": "The Journal of clinical psychiatry",
+ "issn": "1555-2101",
+ "date": "2008-09-09",
+ "abstract": "Obsessive and compulsive symptoms (OCS) are more prevalent in patients with diagnosed Huntington's disease (HD) than in the general population. Although psychiatric symptoms have been reported in individuals with the HD gene expansion prior to clinical diagnosis (pre-HD), little is known about OCS in this phase of disease.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23946314"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19012814"
},
{
- "id": "pmid:23894380",
+ "id": "pmid:18986359",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23894380",
- "title": "The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18986359",
+ "title": "Association of serotonin transporter gene-linked polymorphic region and variable number of tandem repeat polymorphism of the serotonin transporter gene in lichen simplex chronicus patients with psychiatric status.",
"type": "article-journal",
- "doi": "10.1371/journal.pone.0068951",
+ "doi": "10.1111/j.1365-4632.2008.03821.x",
"authors": [
- ["Silke", "Metzger"],
- ["Carolin", "Walter"],
- ["Olaf", "Riess"],
- ["Raymund A C", "Roos"],
- ["J\u00f8rgen E", "Nielsen"],
- ["David", "Craufurd"],
- ["Huu Phuc", "Nguyen"]
+ ["Necmettin", "Kirtak"],
+ ["H Serhat", "Inaloz"],
+ ["Cenk", "Ak\u00e7ali"],
+ ["Emin", "Erdal"],
+ ["Hasan", "Herken"],
+ ["Mehmet", "Yildirim"],
+ ["H Gulcin", "Erguven"]
],
- "publisher": "PloS one",
- "issn": "1932-6203",
- "date": "2013-07-22",
- "abstract": "The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the \"REGISTRY\" cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis.",
+ "publisher": "International journal of dermatology",
+ "issn": "1365-4632",
+ "date": "2008-10-01",
+ "abstract": "The serotonin (5-hydroxytryptamine; 5-HT) is a key neurotransmitter in the central nervous system and a responsible mediator for the itch. Dysregulation of serotonergic pathways has been implicated in the pathogenesis of many complex neuropsychiatric diseases.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23894380"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18986359"
},
{
- "id": "pmid:23847583",
+ "id": "pmid:18854207",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23847583",
- "title": "A Tale of Two Maladies? Pathogenesis of Depression with and without the Huntington's Disease Gene Mutation.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18854207",
+ "title": "Progressive synaptic pathology of motor cortical neurons in a BAC transgenic mouse model of Huntington's disease.",
"type": "article-journal",
- "doi": "10.3389/fneur.2013.00081",
+ "doi": "10.1016/j.neuroscience.2008.09.020",
"authors": [
- ["Xin", "Du"],
- ["Terence Y C", "Pang"],
- ["Anthony J", "Hannan"]
+ ["J", "Spampanato"],
+ ["X", "Gu"],
+ ["X W", "Yang"],
+ ["I", "Mody"]
],
- "publisher": "Frontiers in neurology",
- "issn": "1664-2295",
- "date": "2013-07-09",
- "abstract": "Huntington's disease (HD) is an autosomal dominant disorder caused by a tandem repeat expansion encoding an expanded tract of glutamines in the huntingtin protein. HD is progressive and manifests as psychiatric symptoms (including depression), cognitive deficits (culminating in dementia), and motor abnormalities (including chorea). Having reached the twentieth anniversary of the discovery of the \"genetic stutter\" which causes HD, we still lack sophisticated insight into why so many HD patients exhibit affective disorders such as depression at very early stages, prior to overt appearance of motor deficits. In this review, we will focus on depression as the major psychiatric manifestation of HD, discuss potential mechanisms of pathogenesis identified from animal models, and compare depression in HD patients with that of the wider gene-negative population. The discovery of depressive-like behaviors as well as cellular and molecular correlates of depression in transgenic HD mice has added strong support to the hypothesis that the HD mutation adds significantly to the genetic load for depression. A key question is whether HD-associated depression differs from that in the general population. Whilst preclinical studies, clinical data, and treatment responses suggest striking similarities, there are also some apparent differences. We discuss various molecular and cellular mechanisms which may contribute to depression in HD, and whether they may generalize to other depressive disorders. The autosomal dominant nature of HD and the existence of models with excellent construct validity provide a unique opportunity to understand the pathogenesis of depression and associated gene-environment interactions. Thus, understanding the pathogenesis of depression in HD may not only facilitate tailored therapeutic approaches for HD sufferers, but may also translate to the clinical depression which devastates the lives of so many people.",
+ "publisher": "Neuroscience",
+ "issn": "0306-4522",
+ "date": "2008-09-18",
+ "abstract": "Huntington's disease (HD) is a neurodegenerative disorder caused by a polyglutamine repeat expansion in huntingtin. A newly developed bacterial artificial chromosome transgenic mouse model (BACHD) reproduces phenotypic features of HD including predominantly neuropil-associated protein aggregation and progressive motor dysfunction with selective neurodegenerative pathology. Motor dysfunction has been shown to precede neuropathology in BACHD mice. We therefore investigated the progression of synaptic pathology in pyramidal cells and interneurons of the superficial motor cortex of BACHD mice. Whole-cell patch clamp recordings were performed on layer 2/3 primary motor cortical pyramidal cells and parvalbumin interneurons from BACHD mice at 3 months, when the mice begin to demonstrate mild motor dysfunction, and at 6 months, when the motor dysfunction is more severe. Changes in synaptic variances were detectable at 3 months, and at 6 months BACHD mice display progressive synaptic pathology in the form of reduced cortical excitation and loss of inhibition onto pyramidal cells. These results suggest that progressive alterations of the superficial cortical circuitry may contribute to the decline of motor function in BACHD mice. The synaptic pathology occurs prior to neuronal degeneration and may therefore prove useful as a target for future therapeutic design.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23847583"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18854207"
},
{
- "id": "pmid:23765727",
+ "id": "pmid:18844975",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23765727",
- "title": "Allele-specific expression of the serotonin transporter and its transcription factors following lamotrigine treatment in vitro.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18844975",
+ "title": "Mutant huntingtin activates Nrf2-responsive genes and impairs dopamine synthesis in a PC12 model of Huntington's disease.",
"type": "article-journal",
- "doi": "10.1002/ajmg.b.32178",
+ "doi": "10.1186/1471-2199-9-84",
"authors": [
- ["Ursula M", "D'Souza"],
- ["Georgia", "Powell-Smith"],
- ["Kate", "Haddley"],
- ["Timothy R", "Powell"],
- ["Vivien J", "Bubb"],
- ["Tom", "Price"],
- ["Peter", "McGuffin"],
- ["John P", "Quinn"],
- ["Anne E", "Farmer"]
+ ["Willeke M C", "van Roon-Mom"],
+ ["Barry A", "Pepers"],
+ ["Peter A C", "'t Hoen"],
+ ["Carola A C M", "Verwijmeren"],
+ ["Johan T", "den Dunnen"],
+ ["Josephine C", "Dorsman"],
+ ["Gertjan B", "van Ommen"]
],
- "publisher": "American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics",
- "issn": "1552-485X",
- "date": "2013-06-14",
- "abstract": "Lamotrigine, a mood stabilizer used clinically in the treatment of bipolar disorder, is thought to exert actions on the serotonin system. However lamotrigine's exact mechanism of action remains unclear. The current study investigated whether lamotrigine might exert its effects through altering the expression of the serotonin transporter (5-HTT) gene and its regulatory transcription factors Y box binding protein 1 (YB-1) and CCCTC-binding factor (CTCF). We further considered whether functional variable number tandem repeat (VNTR) polymorphisms in the promoter region of 5-HTT, (5-HTTLPR) and within intron 2 (Stin2) of the gene, moderated any putative gene expression changes. The study employed an in vitro design carried out in human lymphoblastoid cell lines (LCLs) to investigate the effects of lamotrigine treatment at 0.04, 0.2, and 0.4\u2009mM doses for 24\u2009hr on the mRNA expression of 5-HTT, YB-1, and CTCF. LCLs were selected based on combinations of haplotypes of the two VNTRs in the serotonin transporter gene; creating low-expressing and high-expressing LCL groups. Ubiquitin C (UBC) and topoisomerase I (TOP1) genes were found to be the most stably expressed housekeeping genes in drug-treated LCLs. Subsequently, quantitative PCR revealed that higher doses of lamotrigine significantly lowered 5-HTT expression and increased CTCF expression. Haplotype-specific differences in CTCF expression were found in response to lamotrigine, with strongest expression changes observed in the high-expressing LCLs. These data provide an allele-specific in vitro model for examining the molecular targets of lamotrigine, and support the important role of the serotonin transporter gene in its clinical mechanism of action.",
+ "publisher": "BMC molecular biology",
+ "issn": "1471-2199",
+ "date": "2008-10-09",
+ "abstract": "Huntington's disease is a progressive autosomal dominant neurodegenerative disorder that is caused by a CAG repeat expansion in the HD or Huntington's disease gene. Although micro array studies on patient and animal tissue provide valuable information, the primary effect of mutant huntingtin will inevitably be masked by secondary processes in advanced stages of the disease. Thus, cell models are instrumental to study early, direct effects of mutant huntingtin. mRNA changes were studied in an inducible PC12 model of Huntington's disease, before and after aggregates became visible, to identify groups of genes that could play a role in the early pathology of Huntington's disease.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23765727"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18844975"
},
{
- "id": "pmid:23644918",
+ "id": "pmid:18754766",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23644918",
- "title": "Candidate glutamatergic and dopaminergic pathway gene variants do not influence Huntington's disease motor onset.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18754766",
+ "title": "Altered frontostriatal coupling in pre-manifest Huntington's disease: effects of increasing cognitive load.",
"type": "article-journal",
- "doi": "10.1007/s10048-013-0364-y",
+ "doi": "10.1111/j.1468-1331.2008.02253.x",
"authors": [
- ["Eliana Marisa", "Ramos"],
- ["Jeanne C", "Latourelle"],
- ["Tammy", "Gillis"],
- ["Jayalakshmi S", "Mysore"],
- ["Ferdinando", "Squitieri"],
- ["Alba", "Di Pardo"],
- ["Stefano", "Di Donato"],
- ["Cinzia", "Gellera"],
- ["Michael R", "Hayden"],
- ["Patrick J", "Morrison"],
- ["Martha", "Nance"],
- ["Christopher A", "Ross"],
- ["Russell L", "Margolis"],
- ["Estrella", "Gomez-Tortosa"],
- ["Carmen", "Ayuso"],
- ["Oksana", "Suchowersky"],
- ["Ronald J", "Trent"],
- ["Elizabeth", "McCusker"],
- ["Andrea", "Novelletto"],
- ["Marina", "Frontali"],
- ["Randi", "Jones"],
- ["Tetsuo", "Ashizawa"],
- ["Samuel", "Frank"],
- ["Marie-Helene", "Saint-Hilaire"],
- ["Steven M", "Hersch"],
- ["Herminia D", "Rosas"],
- ["Diane", "Lucente"],
- ["Madaline B", "Harrison"],
- ["Andrea", "Zanko"],
- ["Ruth K", "Abramson"],
- ["Karen", "Marder"],
- ["James F", "Gusella"],
- ["Jong-Min", "Lee"],
- ["Isabel", "Alonso"],
- ["Jorge", "Sequeiros"],
- ["Richard H", "Myers"],
- ["Marcy E", "Macdonald"]
+ ["R C", "Wolf"],
+ ["F", "Sambataro"],
+ ["N", "Vasic"],
+ ["C", "Sch\u00f6nfeldt-Lecuona"],
+ ["D", "Ecker"],
+ ["B", "Landwehrmeyer"]
],
- "publisher": "Neurogenetics",
- "issn": "1364-6753",
- "date": "2013-05-04",
- "abstract": "Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and behavioral disturbances. It is caused by the expansion of the HTT CAG repeat, which is the major determinant of age at onset (AO) of motor symptoms. Aberrant function of N-methyl-D-aspartate receptors and/or overexposure to dopamine has been suggested to cause significant neurotoxicity, contributing to HD pathogenesis. We used genetic association analysis in 1,628 HD patients to evaluate candidate polymorphisms in N-methyl-D-aspartate receptor subtype genes (GRIN2A rs4998386 and rs2650427, and GRIN2B rs1806201) and functional polymorphisms in genes in the dopamine pathway (DAT1 3' UTR 40-bp variable number tandem repeat (VNTR), DRD4 exon 3 48-bp VNTR, DRD2 rs1800497, and COMT rs4608) as potential modifiers of the disease process. None of the seven polymorphisms tested was found to be associated with significant modification of motor AO, either in a dominant or additive model, after adjusting for ancestry. The results of this candidate-genetic study therefore do not provide strong evidence to support a modulatory role for these variations within glutamatergic and dopaminergic genes in the AO of HD motor manifestations.",
+ "publisher": "European journal of neurology",
+ "issn": "1468-1331",
+ "date": "2008-08-27",
+ "abstract": "Functional neuroimaging studies have suggested a dysfunction of prefrontal regions in clinically pre-symptomatic individuals with the Huntington's disease (HD) gene mutation (pre-HD) during cognitive processing. The objective of this study was to test the impact of cognitive demand on prefrontal connectivity in pre-HD individuals.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23644918"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18754766"
},
{
- "id": "pmid:23624566",
+ "id": "pmid:18608348",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23624566",
- "title": "Characterization of the Huntington intermediate CAG repeat expansion phenotype in PHAROS.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18608348",
+ "title": "Insufficient ex vivo expansion of Valpha24(+) natural killer T cells in malignant lymphoma patients related to the suppressed expression of CD1d molecules on CD14(+) cells.",
"type": "article-journal",
- "doi": "10.1212/wnl.0b013e318294b304",
+ "doi": "10.1080/14653240802072747",
"authors": [
- ["Annie", "Killoran"],
- ["Kevin M", "Biglan"],
- ["Joseph", "Jankovic"],
- ["Shirley", "Eberly"],
- ["Elise", "Kayson"],
- ["David", "Oakes"],
- ["Anne B", "Young"],
- ["Ira", "Shoulson"]
+ ["O", "Imataki"],
+ ["Y", "Heike"],
+ ["H", "Makiyama"],
+ ["A", "Iizuka"],
+ ["Y", "Ikarashi"],
+ ["T", "Ishida"],
+ ["H", "Wakasugi"],
+ ["Y", "Takaue"]
],
- "publisher": "Neurology",
- "issn": "1526-632X",
- "date": "2013-04-26",
- "abstract": "We aimed to describe the clinical phenotype conferred by the intermediate-length huntingtin allele CAG repeat expansion in a population-based study.",
+ "publisher": "Cytotherapy",
+ "issn": "1477-2566",
+ "date": "2008-01-01",
+ "abstract": "Valpha24(+) natural killer T (NKT) cell is a human counterpart of mice Valpha14(+) NKT cell that has a regulatory role for innate and acquired potential antitumor activity. The efficient expansion of NKT cells is an obstacle to the clinical application of Valpha24(+) NKT cells for immunotherapy.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23624566"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18608348"
},
{
- "id": "pmid:23595883",
+ "id": "pmid:18512767",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23595883",
- "title": "Dominant effects of the Huntington's disease HTT CAG repeat length are captured in gene-expression data sets by a continuous analysis mathematical modeling strategy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18512767",
+ "title": "The relationship between CAG repeat length and clinical progression in Huntington's disease.",
"type": "article-journal",
- "doi": "10.1093/hmg/ddt176",
+ "doi": "10.1002/mds.21988",
"authors": [
- ["Jong-Min", "Lee"],
- ["Ekaterina I", "Galkina"],
- ["Rachel M", "Levantovsky"],
- ["Elisa", "Fossale"],
- ["Mary", "Anne Anderson"],
- ["Tammy", "Gillis"],
- ["Jayalakshmi", "Srinidhi Mysore"],
- ["Kathryn R", "Coser"],
- ["Toshi", "Shioda"],
- ["Bin", "Zhang"],
- ["Matthew D", "Furia"],
- ["Jonathan", "Derry"],
- ["Isaac S", "Kohane"],
- ["Ihn Sik", "Seong"],
- ["Vanessa C", "Wheeler"],
- ["James F", "Gusella"],
- ["Marcy E", "MacDonald"]
+ ["Bernard", "Ravina"],
+ ["Megan", "Romer"],
+ ["Radu", "Constantinescu"],
+ ["Kevin", "Biglan"],
+ ["Alicia", "Brocht"],
+ ["Karl", "Kieburtz"],
+ ["Ira", "Shoulson"],
+ ["Michael P", "McDermott"]
],
- "publisher": "Human molecular genetics",
- "issn": "1460-2083",
- "date": "2013-04-16",
- "abstract": "In Huntington's disease (HD), the size of the expanded HTT CAG repeat mutation is the primary driver of the processes that determine age at onset of motor symptoms. However, correlation of cellular biochemical parameters also extends across the normal repeat range, supporting the view that the CAG repeat represents a functional polymorphism with dominant effects determined by the longer allele. A central challenge to defining the functional consequences of this single polymorphism is the difficulty of distinguishing its subtle effects from the multitude of other sources of biological variation. We demonstrate that an analytical approach based upon continuous correlation with CAG size was able to capture the modest (\u223c21%) contribution of the repeat to the variation in genome-wide gene expression in 107 lymphoblastoid cell lines, with alleles ranging from 15 to 92 CAGs. Furthermore, a mathematical model from an iterative strategy yielded predicted CAG repeat lengths that were significantly positively correlated with true CAG allele size and negatively correlated with age at onset of motor symptoms. Genes negatively correlated with repeat size were also enriched in a set of genes whose expression were CAG-correlated in human HD cerebellum. These findings both reveal the relatively small, but detectable impact of variation in the CAG allele in global data in these peripheral cells and provide a strategy for building multi-dimensional data-driven models of the biological network that drives the HD disease process by continuous analysis across allelic panels of neuronal cells vulnerable to the dominant effects of the HTT CAG repeat.",
+ "publisher": "Movement disorders : official journal of the Movement Disorder Society",
+ "issn": "1531-8257",
+ "date": "2008-07-15",
+ "abstract": "The objective of this study was to examine the relationship between CAG repeat length (CAGn) and clinical progression in patients with Huntington's disease (HD). There are conflicting reports about the relationship between CAGn and clinical progression of HD. We conducted an analysis of data from the Coenzyme Q10 and Remacemide Evaluation in Huntington's Disease (CARE-HD) clinical trial. We modeled progression over 30 months on the Unified Huntington's Disease Rating Scale (UHDRS) and supplemental neuropsychological and behavioral tests using multiple linear regression. Mean subject age was 47.9 +/- 10.5 years and mean CAGn was 45.0 +/- 4.1. Multiple linear regression revealed statistically significant associations between CAGn and worsening on several motor, cognitive, and functional outcomes, but not behavioral outcomes. Many effects were clinically important; 10 additional CAG repeats were associated with an 81% increase in progression on the Independence Scale. These associations were not observed in the absence of age adjustment. Age at the time of assessment confounds the association between CAGn and progression. Adjusting for age shows that longer CAGn is associated with greater clinical progression of HD. This finding may account for the variable results from previous studies examining CAGn and progression. Adjusting for CAGn may be important for clinical trials.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23595883"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18512767"
},
{
- "id": "pmid:23576953",
+ "id": "pmid:18502655",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23576953",
- "title": "Characterization of forebrain neurons derived from late-onset Huntington's disease human embryonic stem cell lines.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18502655",
+ "title": "Full length mutant huntingtin is required for altered Ca2+ signaling and apoptosis of striatal neurons in the YAC mouse model of Huntington's disease.",
"type": "article-journal",
- "doi": "10.3389/fncel.2013.00037",
+ "doi": "10.1016/j.nbd.2008.03.010",
"authors": [
- ["Jonathan C", "Niclis"],
- ["Anita", "Pinar"],
- ["John M", "Haynes"],
- ["Walaa", "Alsanie"],
- ["Robert", "Jenny"],
- ["Mirella", "Dottori"],
- ["David S", "Cram"]
+ ["Hua", "Zhang"],
+ ["Qin", "Li"],
+ ["Rona K", "Graham"],
+ ["Elizabeth", "Slow"],
+ ["Michael R", "Hayden"],
+ ["Ilya", "Bezprozvanny"]
],
- "publisher": "Frontiers in cellular neuroscience",
- "issn": "1662-5102",
- "date": "2013-04-05",
- "abstract": "Huntington's disease (HD) is an incurable neurodegenerative disorder caused by a CAG repeat expansion in exon 1 of the Huntingtin (HTT) gene. Recently, induced pluripotent stem cell (iPSC) lines carrying atypical and aggressive (CAG60+) HD variants have been generated and exhibit disparate molecular pathologies. Here we investigate two human embryonic stem cell (hESC) lines carrying CAG37 and CAG51 typical late-onset repeat expansions in comparison to wildtype control lines during undifferentiated states and throughout forebrain neuronal differentiation. Pluripotent HD lines demonstrate growth, viability, pluripotent gene expression, mitochondrial activity and forebrain specification that is indistinguishable from control lines. Expression profiles of crucial genes known to be dysregulated in HD remain unperturbed in the presence of mutant protein and throughout differentiation; however, elevated glutamate-evoked responses were observed in HD CAG51 neurons. These findings suggest typical late-onset HD mutations do not alter pluripotent parameters or the capacity to generate forebrain neurons, but that such progeny may recapitulate hallmarks observed in established HD model systems. Such HD models will help further our understanding of the cascade of pathological events leading to disease onset and progression, while simultaneously facilitating the identification of candidate HD therapeutics.",
+ "publisher": "Neurobiology of disease",
+ "issn": "1095-953X",
+ "date": "2008-04-16",
+ "abstract": "Huntington's disease (HD) is caused by a progressive loss of striatal medium spiny neurons (MSN). The molecular trigger of HD is a polyglutamine expansion in the Huntingtin protein (Htt). The mutant Htt protein forms insoluble nuclear aggregates which have been proposed to play a key role in causing neuronal cell death in HD. Other lines of investigation suggest that expression of mutant Htt facilitates activity of the NR2B subtype of NMDA receptors and the type 1 inositol 1,4,5-trisphosphate receptors (InsP(3)R1), and that disturbed calcium (Ca(2+)) signaling causes apoptosis of MSNs in HD. The YAC128 transgenic HD mouse model expresses the full-length human Htt protein with 120Q CAG repeat expansion and displays an age-dependent loss of striatal neurons as seen in human HD brain. In contrast, the shortstop mice express an amino-terminal fragment of the mutant Htt protein (exons 1 and 2) and display no behavioral abnormalities or striatal neurodegeneration despite widespread formation of neuronal inclusions. Here we compared Ca(2+) signals in primary MSN neuronal cultures derived from YAC128 and shortstop mice to their wild-type non-transgenic littermates. Repetitive application of glutamate results in supranormal Ca(2+) responses in YAC128 MSNs, but not in shortstop MSNs. In addition, while currents mediated by the NR2B subtype of NMDA receptors were increased in YAC128 MSNs, currents in SS MSNs were found to be similar to WT. Furthermore, YAC128 MSNs were sensitized to glutamate-induced apoptosis. Consistent with these findings, we found that application of glutamate induced rapid loss of mitochondrial membrane potential in YAC128 MSNs. In contrast, SS MSNs do not show increased cell death postglutamate treatment nor accelerated loss of mitochondrial membrane potential following glutamate stimulation. Glutamate-induced loss of mitochondrial membrane potential in YAC128 MSNs could be prevented by inhibitors of NR2B NMDA receptors and mGluR1/5 receptors. Our results are consistent with the hypothesis that disturbed neuronal Ca(2+) signaling plays a significant role in the degeneration of MSN containing full-length mutant Htt(exp). Furthermore, the results obtained with neurons from shortstop mice provide additional evidence that not all fragments of mutant Htt(exp) are toxic to neurons.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23576953"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18502655"
},
{
- "id": "pmid:23480802",
+ "id": "pmid:18413470",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23480802",
- "title": "Biomarkers for Huntington's disease: an update.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18413470",
+ "title": "Rapid eye movement sleep disturbances in Huntington disease.",
"type": "article-journal",
- "doi": "10.1517/17530059.2012.701205",
+ "doi": "10.1001/archneur.65.4.482",
"authors": [
- ["Rachael I", "Scahill"],
- ["Ed J", "Wild"],
- ["Sarah J", "Tabrizi"]
+ ["Isabelle", "Arnulf"],
+ ["J\u00f8rgen", "Nielsen"],
+ ["Ebba", "Lohmann"],
+ ["Johannes", "Schiefer"],
+ ["Edward", "Wild"],
+ ["Poul", "Jennum"],
+ ["Eric", "Konofal"],
+ ["Matthew", "Walker"],
+ ["Delphine", "Oudiette"],
+ ["Sarah", "Tabrizi"],
+ ["Alexandra", "Durr"]
],
- "publisher": "Expert opinion on medical diagnostics",
- "issn": "1753-0067",
- "date": "2012-06-24",
- "abstract": "Huntington's disease (HD) is a devastating autosomal-dominant neurodegenerative condition caused by a CAG repeat expansion in the gene encoding huntingtin which is characterised by progressive motor impairment, cognitive decline and neuropsychiatric disturbances. There are currently no disease-modifying treatments available to patients, but a number of therapeutic strategies are currently being investigated, chief among them are nucleotide-based 'gene silencing' approaches, modulation of huntingtin post-translation modification and enhancing clearance of the mutant protein. In 2008, the authors' review highlighted the need to develop and validate biomarkers and provided a systematic head-to-head comparison of such measures. They searched the PubMed database for publications, which covered each of the subheadings mentioned below. They identified from these list studies which had relevance to biomarker development, as defined in their previous review. Building on a tradition of collaborative research in HD, great advances have been made in the field since that time and a range of outcome measures are now being recommended in order to assess efficacy in future therapeutic trials.",
+ "publisher": "Archives of neurology",
+ "issn": "1538-3687",
+ "date": "2008-04-01",
+ "abstract": "Sleep disorders including insomnia, movements during sleep, and daytime sleepiness are common but poorly studied in Huntington disease (HD).",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23480802"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18413470"
},
{
- "id": "pmid:23443539",
+ "id": "pmid:18403212",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23443539",
- "title": "Translation of HTT mRNA with expanded CAG repeats is regulated by the MID1-PP2A protein complex.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18403212",
+ "title": "Sertraline slows disease progression and increases neurogenesis in N171-82Q mouse model of Huntington's disease.",
"type": "article-journal",
- "doi": "10.1038/ncomms2514",
+ "doi": "10.1016/j.nbd.2008.01.015",
"authors": [
- ["Sybille", "Krauss"],
- ["Nadine", "Griesche"],
- ["Ewa", "Jastrzebska"],
- ["Changwei", "Chen"],
- ["D\u00e9siree", "Rutschow"],
- ["Clemens", "Achm\u00fcller"],
- ["Stephanie", "Dorn"],
- ["Sylvia M", "Boesch"],
- ["Maciej", "Lalowski"],
- ["Erich", "Wanker"],
- ["Rainer", "Schneider"],
- ["Susann", "Schweiger"]
+ ["Wenzhen", "Duan"],
+ ["Qi", "Peng"],
+ ["Naoki", "Masuda"],
+ ["Eric", "Ford"],
+ ["Erik", "Tryggestad"],
+ ["Bruce", "Ladenheim"],
+ ["Ming", "Zhao"],
+ ["Jean Lud", "Cadet"],
+ ["John", "Wong"],
+ ["Christopher A", "Ross"]
],
- "publisher": "Nature communications",
- "issn": "2041-1723",
- "date": "2013-01-01",
- "abstract": "Expansion of CAG repeats is a common feature of various neurodegenerative disorders, including Huntington's disease. Here we show that expanded CAG repeats bind to a translation regulatory protein complex containing MID1, protein phosphatase 2A and 40S ribosomal S6 kinase. Binding of the MID1-protein phosphatase 2A protein complex increases with CAG repeat size and stimulates translation of the CAG repeat expansion containing messenger RNA in a MID1-, protein phosphatase 2A- and mammalian target of rapamycin-dependent manner. Our data indicate that pathological CAG repeat expansions upregulate protein translation leading to an overproduction of aberrant protein and suggest that the MID1-complex may serve as a therapeutic target for the treatment of CAG repeat expansion disorders.",
+ "publisher": "Neurobiology of disease",
+ "issn": "1095-953X",
+ "date": "2008-03-10",
+ "abstract": "Huntington's disease (HD) is an inherited progressive neurodegenerative disorder resulting from CAG repeat expansion in the gene that encodes for the protein huntingtin. To identify neuroprotective compound (s) that can slow down disease progression and can be administered long term with few side effects in Huntington's disease, we investigated the effect of sertraline, a selective serotonin reuptake inhibitor (SSRI) which has been shown to upregulate BDNF levels in rodent brains. We report here that in HD mice sertraline increased BDNF levels, preserved chaperone protein HSP70 and Bcl-2 levels in brains, attenuated the progression of brain atrophy and behavioral abnormalities and thereby increased survival. Sertraline also enhanced neurogenesis, which appeared to be responsible for mediating the beneficial effects of sertraline in HD mice. Additionally, the effective levels of sertraline are comparable to the safe levels achievable in humans. The findings suggest that sertraline is a potential candidate for treatment of HD patients.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23443539"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18403212"
},
{
- "id": "pmid:23440000",
+ "id": "pmid:18403126",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23440000",
- "title": "Intermediate CAG Repeats in Huntington's Disease: Analysis of COHORT.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18403126",
+ "title": "Dopamine D1 receptor-mediated aggregation of N-terminal fragments of mutant huntingtin and cell death in a neuroblastoma cell line.",
"type": "article-journal",
- "doi": "10.7916/d8ff3r2p",
+ "doi": "10.1016/j.neuroscience.2008.02.052",
"authors": [
- ["Ainhi D", "Ha"],
- ["Christopher A", "Beck"],
- ["Joseph", "Jankovic"]
+ ["P", "Robinson"],
+ ["M", "Lebel"],
+ ["M", "Cyr"]
],
- "publisher": "Tremor and other hyperkinetic movements (New York, N.Y.)",
- "issn": "2160-8288",
- "date": "2012-02-02",
- "abstract": "There is emerging evidence that clinical and neuro-pathological manifestations of Huntington's disease (HD) may occur in individuals with intermediate length cytosine-adenine-guanine (CAG) repeats (27-35 CAG repeats) in the Huntingtin (HTT) gene. We aim to further define the clinical characteristics of individuals who possess CAG repeat lengths in this range.",
+ "publisher": "Neuroscience",
+ "issn": "1873-7544",
+ "date": "2008-03-06",
+ "abstract": "Huntington's disease (HD) is an inherited neurodegenerative disorder caused by abnormal CAG repeat expansion in the IT15 gene encoding huntingtin protein (htt). Mutated htt is predicted to acquire toxic properties in specific brain regions. For instance, striatal neurons expressing dopamine receptors predominantly degenerate in HD patients. Although the basis of this specific vulnerability remains unclear, a great deal of evidence has documented the ability of the dopamine system to modulate the toxicity of expanded htt. To investigate the relationship between dopamine receptors and expanded htt, we transfected enhanced green fluorescent proteins (EGFP) tagged to normal (25 CAG) or mutant (103 CAG) htt in SK-N-MC neuroblastoma cells that endogenously express D1 receptors. Forming nuclear and cytoplasmic aggregates, mutant htt-EGFP was toxic to cells beyond 24 h post-transfection. Remarkably, low doses of a selective D1 receptors agonist or forskolin, an activator of adenylate cyclase, accelerated the formation of mutant htt nuclear aggregates, whereas the number of cytoplasmic aggregates was decreased. These effects were associated with a minor increase in cell death. Understanding the functional bases of these effects may further elucidate the role of dopamine receptors signaling in the complex pathophysiology of HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23440000"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18403126"
},
{
- "id": "pmid:23398026",
+ "id": "pmid:18349696",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23398026",
- "title": "Clinical features of Chinese patients with Huntington's disease carrying CAG repeats beyond 60 within HTT gene.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18349696",
+ "title": "Low level of harm avoidance is associated with serotonin transporter functional haplotype in alcohol-dependent individuals.",
"type": "article-journal",
- "doi": "10.1111/cge.12120",
+ "doi": "10.1097/ypg.0b013e3282f60333",
"authors": [
- ["Z-J", "Liu"],
- ["Y-M", "Sun"],
- ["W", "Ni"],
- ["Y", "Dong"],
- ["S-S", "Shi"],
- ["Z-Y", "Wu"]
+ ["Gabi", "Koller"],
+ ["Peter", "Zill"],
+ ["Thomas", "Skoruppa"],
+ ["Brigitta", "Bondy"],
+ ["Ulrich W", "Preuss"],
+ ["Michael", "Soyka"]
],
- "publisher": "Clinical genetics",
- "issn": "1399-0004",
- "date": "2013-03-11",
- "abstract": "Patients with Huntington's disease (HD) carrying CAG repeats beyond 60 are less frequently seen and clinical features of them have been rarely reported. We identified four unrelated patients carrying CAG repeats beyond 60 (84.0 \u00b1 13.76, ranging from 74 to 104) from 119 Chinese HD patients via direct sequencing. These four were all early onset with a mean age at presenting symptom of 9.8 \u00b1 1.71 years. Paternal transmission was found in three of them and the fourth was apparently sporadic. In addition, they had atypical onset symptoms including epilepsy, intellectual decline, tics and walking instability, which might lead the clinicians to make the wrong diagnosis in the early stage of disease. Our work explores clinical features of Chinese HD patients with an expanded CAG repeat over 60 and may help the clinicians make a correct diagnosis in the early stage of disease.",
+ "publisher": "Psychiatric genetics",
+ "issn": "1473-5873",
+ "date": "2008-04-01",
+ "abstract": "The serotonin transporter gene (SLC6A4) encodes a trans-membrane protein (5-HTT) that plays an important role in regulating serotonergic neurotransmission, which is known to be involved in many psychiatric disorders. A polymorphism in the transcriptional control region containing long (L) and short (S) variants (5-HTTLPR) as well as alleles of the variable number tandem repeats (VNTR) region were demonstrated. Higher serotonin levels among carriers of the S allele might exhibit increased liability of serotonin-mediated, psychopathology-like anxiety and depression and may impair social skills reflected by harm avoidance.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23398026"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18349696"
},
{
- "id": "pmid:23372043",
+ "id": "pmid:18314311",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23372043",
- "title": "A critical role of astrocyte-mediated nuclear factor-\u03baB-dependent inflammation in Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18314311",
+ "title": "Serotonin transporter gene polymorphisms: effect on serotonin transporter availability in the brain of suicide attempters.",
"type": "article-journal",
- "doi": "10.1093/hmg/ddt036",
+ "doi": "10.1016/j.pscychresns.2007.07.004",
"authors": [
- ["Han-Yun", "Hsiao"],
- ["Yu-Chen", "Chen"],
- ["Hui-Mei", "Chen"],
- ["Pang-Hsien", "Tu"],
- ["Yijuang", "Chern"]
+ ["Jessica", "Bah"],
+ ["Mats", "Lindstr\u00f6m"],
+ ["Lars", "Westberg"],
+ ["Louise", "Manner\u00e5s"],
+ ["Erik", "Ryding"],
+ ["Susanne", "Henningsson"],
+ ["Jonas", "Melke"],
+ ["Ingmar", "Ros\u00e9n"],
+ ["Lil", "Tr\u00e4skman-Bendz"],
+ ["Elias", "Eriksson"]
],
- "publisher": "Human molecular genetics",
- "issn": "1460-2083",
- "date": "2013-01-30",
- "abstract": "Huntington's disease (HD) is an autosomal disease caused by a CAG repeat expansion in the huntingtin (HTT) gene. The resultant mutant HTT protein (mHTT) forms aggregates in various types of cells, including neurons and glial cells and preferentially affects brain function. We found that two HD mouse models (Hdh(150Q) and R6/2) were more susceptible than wild-type (WT) mice to lipopolysaccharide-evoked systemic inflammation and produced more proinflammatory cytokines in the brain. Such an enhanced inflammatory response in the brain was not observed in N171- 82Q mice that express mHTT only in neurons, but not in glial cells. Thus, HD glia might play an important role in chronic inflammation that accelerates disease progression in HD mice. Intriguingly, enhanced activation of nuclear factor (NF)-\u03baB-p65 (p65), a transcriptional mediator of inflammatory responses, was observed in astrocytes of patients and mice with HD. Results obtained using primary R6/2 astrocytes suggest that these cells exhibited higher I\u03baB kinase (IKK) activity that caused prolongation of NF-\u03baB activation, thus upregulating proinflammatory factors during inflammation. R6/2 astrocytes also produced a more-damaging effect on primary R6/2 neurons than did WT astrocytes during inflammation. Blockage of IKK reduced the neuronal toxicity caused by R6/2 astrocytes and ameliorated several HD symptoms of R6/2 mice (e.g. decreased neuronal density, impaired motor coordination and poor cognitive function). Collectively, our results indicate that enhancement of the p65-mediated inflammatory response in astrocytes contributes to HD pathogenesis. Therapeutic interventions aimed at preventing neuronal inflammation may be an important strategy for treating HD.",
+ "publisher": "Psychiatry research",
+ "issn": "0165-1781",
+ "date": "2008-04-15",
+ "abstract": "The efficacy of serotonin reuptake inhibitors in depression and anxiety disorders suggests the gene coding for the serotonin transporter (5-HTT), SLC6A4, as a candidate of importance for these conditions. Positive findings regarding associations between polymorphisms in SLC6A4 have been reported, indicating that these polymorphisms may influence anxiety-related personality traits, as well as the risk of developing depression and suicidality. Serotonin 5-HTT availability was assessed with single photon emission computed tomography (SPECT), using (123)I-beta-CIT as ligand, in a population of unmedicated male suicide attempters (n=9) and in matched controls (n=9). Two polymorphisms in SLC6A4 were assessed, including the 5-HTTLPR located in the promoter region and a variable number of tandem repeats (VNTR) polymorphism in intron 2 (STin2). In suicide attempters, but not in controls, low 5-HTT availability was associated with the S allele of 5-HTTLPR and with the 12 repeat allele of STin2. Data suggest that polymorphisms in SLC6A4 may influence the expression of the brain serotonin transporter in suicide attempters.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23372043"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18314311"
},
{
- "id": "pmid:23346156",
+ "id": "pmid:18307262",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23346156",
- "title": "Decreased Metabolism in the Cerebral Cortex in Early-Stage Huntington's Disease: A Possible Biomarker of Disease Progression?",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18307262",
+ "title": "Huntington's disease as caused by 34 CAG repeats.",
"type": "article-journal",
- "doi": "10.3988/jcn.2013.9.1.21",
+ "doi": "10.1002/mds.21958",
"authors": [
- ["Hyeeun", "Shin"],
- ["Man Ho", "Kim"],
- ["Su Jin", "Lee"],
- ["Kyung-Han", "Lee"],
- ["Mi-Jung", "Kim"],
- ["Ji Sun", "Kim"],
- ["Jin Whan", "Cho"]
+ ["J\u00fcrgen", "Andrich"],
+ ["Larissa", "Arning"],
+ ["Stefan", "Wieczorek"],
+ ["Peter H", "Kraus"],
+ ["Ralf", "Gold"],
+ ["Carsten", "Saft"]
],
- "publisher": "Journal of clinical neurology (Seoul, Korea)",
- "issn": "1738-6586",
- "date": "2013-01-03",
- "abstract": "Huntington's disease (HD) is an autosomal-dominant inherited neurodegenerative disorder. Genetic analysis of abnormal CAG expansion in the IT15 gene allows disease confirmation even in the preclinical stage. However, because there is no treatment to cure or delay the progression of this disease, monitoring of biological markers that predict progression is warranted.",
+ "publisher": "Movement disorders : official journal of the Movement Disorder Society",
+ "issn": "1531-8257",
+ "date": "2008-04-30",
+ "abstract": "Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by an abnormal expansion of a polymorphic stretch of CAG repeats in the coding 5' part of the HD gene on chromosome 4p. Expansions of CAG blocks beyond 35 repeats are associated with the clinical presentation of HD. There is an intermediate range of rare alleles between 27 and 35 CAG repeats with a higher risk for further expansion in subsequent generations. Here, we report a 75-year-old male with clinical features of HD and 34 CAG repeat units.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23346156"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18307262"
},
{
- "id": "pmid:23277128",
+ "id": "pmid:18204817",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23277128",
- "title": "Study of the association of serotonin transporter triallelic 5-HTTLPR and STin2 VNTR polymorphisms with lithium prophylaxis response in bipolar disorder.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18204817",
+ "title": "Interspecies and intraspecies variations in the serotonin transporter gene intron 3 VNTR in nonhuman primates.",
"type": "article-journal",
- "doi": "10.1097/ypg.0b013e32835d6fad",
+ "doi": "10.1007/s10329-007-0077-7",
"authors": [
- ["Hema", "Tharoor"],
- ["Ananthapadmanabha", "Kotambail"],
- ["Sanjeev", "Jain"],
- ["Podila Satya Venkata Narasimha", "Sharma"],
- ["Kapaettu", "Satyamoorthy"]
+ ["Miho", "Inoue-Murayama"],
+ ["Emi", "Hibino"],
+ ["Hiromi", "Iwatsuki"],
+ ["Eiji", "Inoue"],
+ ["Kyung-Won", "Hong"],
+ ["Toshisada", "Nishida"],
+ ["Ikuo", "Hayasaka"],
+ ["Shin'ichi", "Ito"],
+ ["Yuichi", "Murayama"]
],
- "publisher": "Psychiatric genetics",
- "issn": "1473-5873",
- "date": "2013-04-01",
- "abstract": "The 5-hydroxy tryptamine transporter (5-HTT) gene has been previously implicated in lithium response, but the roles of the triallelic 5-HTT linked promoter region (5-HTTLPR) and variable number tandem repeats in the second intron [serotonin transporter intron 2 (STin2)] have not been reported. We examined these polymorphisms in 122 patients with bipolar I disorder, among which 49 patients were classified as good responders, 49 as nonresponders, and 24 as partial responders to lithium prophylaxis. We observed significant variation in the genotype frequencies of STin2 polymorphism among the response groups (P=0.02). There was also a significant association of haplotype consisting of the S allele of 5-HTTLPR and 10 repeat allele of STin2 with lithium response (P=0.01) and no such relationship was found with 5-HTTLPR variants. Our data support preliminary information of a possible association of STin2 and its combined effect with 5-HTTLPR variants with lithium response and also suggest that lithium is likely to be more effective for patients carrying 5-HTT polymorphisms associated with reduced transcriptional activity.",
+ "publisher": "Primates; journal of primatology",
+ "issn": "0032-8332",
+ "date": "2008-01-18",
+ "abstract": "A variable number of tandem repeat (VNTR) polymorphism based on a 16 or 17-bp unit has been reported in the third intron of the human serotonin transporter gene (5-HTT). VNTRs have been shown to affect the transcriptional activity of genes, and VNTR polymorphisms possibly influence human personality and several psychoneurological disorders. To estimate the changes that occurred in the VNTRs during primate evolution, we amplified and sequenced the regions that corresponded to the human VNTRs in various primate species, including apes, Old World monkeys, and New World monkeys. The VNTR sequences were polymorphic in all the ape species examined, and alleles with repeat numbers of 18, 19, 23, and 24 in chimpanzees, 33, 35, 36, 38, and 40 in gorillas, 4 and 6 in orangutans, and 11, 13, 14, and 15 in gibbons were found. On the other hand, only a 5-repeat allele was detected in Old World monkeys such as the Japanese macaque and patas monkey. In this study we demonstrated for the first time that a repeat structure was not present in the corresponding regions in the New World monkeys examined, and only one unit sequence was found in them. These results suggested that the duplication of a unit in the VNTR region occurred in the Cercopithecidae species following the divergence of the Old World and New World monkeys, and various long repeated alleles were generated in humans and apes, except orangutans.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23277128"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18204817"
},
{
- "id": "pmid:25063431",
+ "id": "pmid:18192679",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25063431",
- "title": "Preliminary analysis of Huntington's Disease in South Korea.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18192679",
+ "title": "Huntingtin-associated protein-1 is a modifier of the age-at-onset of Huntington's disease.",
"type": "article-journal",
- "doi": "10.3233/jhd-120040",
+ "doi": "10.1093/hmg/ddn003",
"authors": [
- ["Chae Won", "Shin"],
- ["Yoon Jae", "Choi"],
- ["Manho", "Kim"],
- ["Beom Seok", "Jeon"]
+ ["Silke", "Metzger"],
+ ["Juan", "Rong"],
+ ["Huu-Phuc", "Nguyen"],
+ ["Austin", "Cape"],
+ ["Juergen", "Tomiuk"],
+ ["Anne S", "Soehn"],
+ ["Peter", "Propping"],
+ ["Yun", "Freudenberg-Hua"],
+ ["Jan", "Freudenberg"],
+ ["Liang", "Tong"],
+ ["Shi-Hua", "Li"],
+ ["Xiao-Jiang", "Li"],
+ ["Olaf", "Riess"]
],
- "publisher": "Journal of Huntington's disease",
- "issn": "1879-6397",
- "date": "2013-01-01",
- "abstract": "There have been epidemiological studies of Huntington's disease (HD) in various populations and nations. Only a few studies describing clinical characteristics have been reported in Asia.",
+ "publisher": "Human molecular genetics",
+ "issn": "1460-2083",
+ "date": "2008-01-11",
+ "abstract": "A polyglutamine repeat expansion of more than 36 units in a protein called huntingtin (htt) is the only known cause of Huntington's disease (HD). The expanded repeat length is inversely correlated with the age-at-onset (AAO), however, the onset age among HD patients with CAG repeats below 60 units varies considerably. In addition to environmental factors, genetic factors different from the expanded CAG repeat length can modify the AAO of HD. We hypothezised that htt interacting proteins might contribute to this variation in the AAO and investigated human htt-associated protein-1 (HAP1) using genetic and functional assays. We identified six polymorphisms in the HAP1 gene including one that substitutes methionine (M441) for threonine (T441) at amino acid 441. Analyzing 980 European HD patients, we found that patients homozygous for the M441 genotype show an 8-year delay in the AAO. Functional assays demonstrated that human M441-HAP1 interacts with mutant htt more tightly than does human T441-HAP1, reduces soluble htt degraded products and protects against htt-mediated toxicity. We thus provide genetic and functional evidence that the M441-HAP1 polymorphism modifies the AAO of HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25063431"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18192679"
},
{
- "id": "pmid:23157165",
+ "id": "pmid:19378429",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23157165",
- "title": "CAG/CTG repeats alter the affinity for the histone core and the positioning of DNA in the nucleosome.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19378429",
+ "title": "Use of capillary electrophoresis for accurate determination of CAG repeats causing Huntington disease. An oligonucleotide design avoiding shadow bands.",
"type": "article-journal",
- "doi": "10.1021/bi301416v",
+ "doi": "10.1080/00365510801915171",
"authors": [
- ["Catherine B", "Volle"],
- ["Sarah", "Delaney"]
+ ["Sonia", "Blanco"],
+ ["Antonio", "Suarez"],
+ ["Sandra", "Gandia-Pla"],
+ ["Carolina", "G\u00f3mez-Llorente"],
+ ["Adelaida", "Ant\u00fanez"],
+ ["Jose Antonio", "G\u00f3mez-Capilla"],
+ ["M Esther", "F\u00e1rez-Vidal"]
],
- "publisher": "Biochemistry",
- "issn": "1520-4995",
- "date": "2012-11-27",
- "abstract": "Trinucleotide repeats (TNRs) occur throughout the genome, and their expansion has been linked to several neurodegenerative disorders, including Huntington's disease. TNRs have been studied using both oligonucleotides and plasmids; however, less is know about how repetitive DNA responds to genomic packaging. Here, we investigate the behavior of CAG/CTG repeats incorporated into nucleosome core particles, the most basic unit of chromatin packaging. To assess the general interaction between CAG/CTG repeats and the histone core, we determined the efficiency with which various TNR-containing DNA substrates form nucleosomes, revealing that even short CAG/CTG tracts are robust incorporators. However, the presence of the Huntington gene flanking sequence (htt) decreases the rate of incorporation. Enzymatic and chemical probing revealed repositioning of the DNA in the nucleosome as the number of CAG/CTG repeats increased, regardless of the flanking sequence. Notably, the periodicity of the repeat tract remained unchanged as a function of length and is consistently 10.7 bp per helical turn. In contrast, the periodicity of the nonrepetitive flanking sequence varies and is smaller than the repeat tract at ~10.0-10.5 bp per turn. Furthermore, while the CAG/CTG repeats remain as a canonical duplex in the nucleosome, nucleosome formation causes kinking in a secondary repeat tract in the htt gene, comprised of CCG/CGG repeats. This work highlights the innate ability of CAG/CTG repeats to incorporate and to position in nucleosomes and how that behavior is modulated by the htt flanking sequence. In addition, it illuminates the differences in packaging of healthy and diseased length repeat tracts within the genome.",
+ "publisher": "Scandinavian journal of clinical and laboratory investigation",
+ "issn": "0036-5513",
+ "date": "2008-01-01",
+ "abstract": "Huntington disease (HD) is a neurodegenerative disorder associated with the expansion of a polymorphic trinucleotide CAG repeat in the HD gene. We have developed an assay to accurately determine CAG repeats that combines a novel oligonucleotide design and the resolution of capillary electrophoresis. A mismatch in the second nucleotide from the 3' end enhanced specificity by avoiding mispriming and diminishing shadow bands and artifactual PCR products. The coupling of capillary electrophoresis analysis with the assay added the advantages of accuracy, high resolution, semi-automation, rapid analysis and low sample consumption. Analysis of 200 chromosomes in the Spanish population sample studied (control group) gave a peak frequency for 16 CAG repeats and of 7 triplets for CCG repeats. Diagnosis of HD was confirmed in 22 of 34 individuals with a range of CAG repeats from 39 to 52. Predictive testing was also carried out for 19 relatives of the HD families diagnosed at our laboratory. The method proposed in this article provides an accurate sizing of DNA repeats that can be applied to the analysis of DNA size-related disorders.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23157165"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19378429"
},
{
- "id": "pmid:23008174",
+ "id": "pmid:18091069",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23008174",
- "title": "Huntington's disease: how intermediate are intermediate repeat lengths?",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18091069",
+ "title": "Are cognitive changes progressive in prediagnostic HD?",
"type": "article-journal",
- "doi": "10.1002/mds.25172",
+ "doi": "10.1097/wnn.0b013e31815cfef8",
"authors": [
- ["Ferdinando", "Squitieri"],
- ["Joseph", "Jankovic"]
+ ["Julie C", "Stout"],
+ ["Marjorie", "Weaver"],
+ ["Andrea C", "Solomon"],
+ ["Sarah", "Queller"],
+ ["Siu", "Hui"],
+ ["Shannon A", "Johnson"],
+ ["Jacqueline", "Gray"],
+ ["Xabier", "Beristain"],
+ ["Joanne", "Wojcieszek"],
+ ["Tatiana", "Foroud"]
],
- "publisher": "Movement disorders : official journal of the Movement Disorder Society",
- "issn": "1531-8257",
- "date": "2012-09-24",
- "abstract": "Huntington's disease (HD) is a devastating heredoneurodegenerative disorder associated with a wide variety of neurological and psychiatric symptoms caused by an expanded CAG repeat in the HTT gene. The expansion mutation in HTT is dominantly transmitted and codes for a protein named huntingtin (htt).",
+ "publisher": "Cognitive and behavioral neurology : official journal of the Society for Behavioral and Cognitive Neurology",
+ "issn": "1543-3641",
+ "date": "2007-12-01",
+ "abstract": "To characterize neurocognitive signs of disease progression in prediagnosis and early Huntington disease (HD) and compare the sensitivity of 2 disease staging classification schemes for detecting these signs.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23008174"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18091069"
},
{
- "id": "pmid:22993450",
+ "id": "pmid:18077673",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/22993450",
- "title": "The differential diagnosis of Huntington's disease-like syndromes: 'red flags' for the clinician.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18077673",
+ "title": "Mitochondrial sensitivity and altered calcium handling underlie enhanced NMDA-induced apoptosis in YAC128 model of Huntington's disease.",
"type": "article-journal",
- "doi": "10.1136/jnnp-2012-302532",
+ "doi": "10.1523/jneurosci.3455-07.2007",
"authors": [
- ["Davide", "Martino"],
- ["Maria", "Stamelou"],
- ["Kailash P", "Bhatia"]
+ ["Herman B", "Fernandes"],
+ ["Kenneth G", "Baimbridge"],
+ ["John", "Church"],
+ ["Michael R", "Hayden"],
+ ["Lynn A", "Raymond"]
],
- "publisher": "Journal of neurology, neurosurgery, and psychiatry",
- "issn": "1468-330X",
- "date": "2012-09-19",
- "abstract": "A growing number of progressive heredodegenerative conditions mimic the presentation of Huntington's disease (HD). Differentiating among these HD-like syndromes is necessary when a patient with a combination of movement disorders, cognitive decline, behavioural abnormalities and progressive disease course proves negative to the genetic testing for HD causative mutations, that is, IT15 gene trinucleotide-repeat expansion. The differential diagnosis of HD-like syndromes is complex and may lead to unnecessary and costly investigations. We propose here a guide to this differential diagnosis focusing on a limited number of clinical features ('red flags') that can be identified through accurate clinical examination, collection of historical data and a few routine ancillary investigations. These features include the ethnic background of the patient, the involvement of the facio-bucco-lingual and cervical district by the movement disorder, the co-occurrence of cerebellar features and seizures, the presence of peculiar gait patterns and eye movement abnormalities, and an atypical progression of illness. Additional help may derive from the cognitive-behavioural presentation of the patient, as well as by a restricted number of ancillary investigations, mainly MRI and routine blood tests. These red flags should be constantly updated as the phenotypic characterisation and identification of more reliable diagnostic markers for HD-like syndromes progress over the following years.",
+ "publisher": "The Journal of neuroscience : the official journal of the Society for Neuroscience",
+ "issn": "1529-2401",
+ "date": "2007-12-12",
+ "abstract": "Expansion of a CAG repeat in the Huntington's disease (HD) gene results in progressive neuronal loss, particularly of striatal medium-sized spiny neurons (MSNs). Studies in human HD autopsy brain tissue, as well as cellular and animal models of HD, suggest that increased activity of NMDA-type glutamate receptors and altered mitochondrial function contribute to selective neuronal degeneration. In this regard, the YAC128 mouse model, expressing full-length human huntingtin with 128 glutamine repeats, has been the focus of much interest. Although NMDA-induced apoptosis is enhanced in YAC128 MSNs, here we report that the initial steps in the death signaling pathway, including NMDA receptor (NMDAR) current and cytosolic Ca2+ loading, are similar to those observed in wild-type MSNs. In contrast, we found that the NMDAR-mediated Ca2+ load triggered a strikingly enhanced loss of mitochondrial membrane potential in YAC128 MSNs, suggesting that NMDAR signaling via the mitochondrial apoptotic pathway is altered. This effect was accompanied by impaired cytosolic Ca2+ clearance after removal of NMDA, a difference that was not apparent after high potassium-evoked depolarization-mediated Ca2+ entry. Inhibition of the mitochondrial permeability transition (mPT) reduced peak cytosolic Ca2+ and mitochondrial depolarization evoked by NMDA in YAC128 MSNs but not wild-type MSNs. Hence, in contrast to YAC models with moderate CAG expansions, the enhanced NMDA-induced apoptosis in YAC128 MSNs is predominantly determined by augmented mitochondrial sensitivity to Ca2+-induced activation of the mPT. These results suggest that the CAG repeat length influences the mechanism by which mHtt enhances NMDAR-mediated excitotoxicity.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22993450"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18077673"
},
{
- "id": "pmid:22985800",
+ "id": "pmid:18068007",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/22985800",
- "title": "Abnormal apocrine secretory cell mitochondria in a Huntington disease patient.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18068007",
+ "title": "Analysis of CCG repeats in Huntingtin gene among HD patients and normal populations in Japan.",
"type": "article-journal",
- "doi": "10.1016/j.jns.2012.08.034",
+ "doi": "10.1016/j.arcmed.2007.06.015",
"authors": [
- ["Christos", "Sidiropoulos"],
- ["Peter", "LeWitt"],
- ["Ken", "Hashimoto"]
+ ["Saeid", "Morovvati"],
+ ["Masanori", "Nakagawa"],
+ ["Mitsuhiro", "Osame"],
+ ["Ali", "Karami"]
],
- "publisher": "Journal of the neurological sciences",
- "issn": "1878-5883",
- "date": "2012-09-15",
- "abstract": "Over two decades, a 42-year old woman experienced the gradual onset of choreic involuntary movements, dystonia, and tics. Decreased caudate nucleus metabolism on 2-deoxyglucose PET scan and a heterozygous 49-CAG repeat expansion within the HTT gene established the diagnosis of HD, although no other family history was known. An axillary skin biopsy revealed a distinctive abnormality of mitochondria limited to the apocrine secretory cells on electron microscopy. All mitochondria were transformed into rounded structures with disrupted cristae and prominent myelin figures; many were enlarged up to 4 times the normal. Cytoplasm of apocrine secretory cells showed an abundance of lipid vacuoles, empty vesicles, and dense bodies. Biopsied skeletal muscle histology (light microscopy) was normal, as was a mitochondrial metabolism study. Biopsies from other HD patients have shown similar mitochondrial changes in cerebral neurons, muscle, fibroblasts, and lymphoblasts, adding to evidence for a systemic disturbance of mitochondria in HD.",
+ "publisher": "Archives of medical research",
+ "issn": "0188-4409",
+ "date": "2007-08-23",
+ "abstract": "Huntington's disease (HD) is a hereditary autosomal dominant neurodegenerative disease characterized by motor, cognitive, and psychiatric symptoms. The molecular basis of the disease is the expansion of the trinucleotide CAG in the first exon of a gene on chromosome four (4p 16.3). There is another triplet sequence, a CCG repeat, immediately 3' adjacent to the CAG repeat in Huntingtin. This triplet sequence is also polymorphic, alleles of 7 or 10 repeats are predominant in populations, and strong linkage disequilibrium between the CCG (7) allele and HD has been shown in western HD chromosomes, whereas Japanese HD chromosomes strongly associate with an allele of (CCG)10.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22985800"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18068007"
},
{
- "id": "pmid:22814437",
+ "id": "pmid:17952586",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/22814437",
- "title": "Replacement of huntingtin exon 1 by trans-splicing.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17952586",
+ "title": "Huntington's disease and mitochondrial DNA deletions: event or regular mechanism for mutant huntingtin protein and CAG repeats expansion?!",
"type": "article-journal",
- "doi": "10.1007/s00018-012-1083-5",
+ "doi": "10.1007/s10571-007-9206-5",
"authors": [
- ["Hansj\u00f6rg", "Rindt"],
- ["Pei-Fen", "Yen"],
- ["Christina N", "Thebeau"],
- ["Troy S", "Peterson"],
- ["Gary A", "Weisman"],
- ["Christian L", "Lorson"]
+ ["Mohammad Mehdi", "Banoei"],
+ ["Massoud", "Houshmand"],
+ ["Mehdi Shafa Shariat", "Panahi"],
+ ["Parvin", "Shariati"],
+ ["Maryam", "Rostami"],
+ ["Masoumeh Dehghan", "Manshadi"],
+ ["Tayebeh", "Majidizadeh"]
],
- "publisher": "Cellular and molecular life sciences : CMLS",
- "issn": "1420-9071",
- "date": "2012-07-20",
- "abstract": "Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder caused by polyglutamine expansion in the amino-terminus of huntingtin (HTT). HD offers unique opportunities for promising RNA-based therapeutic approaches aimed at reducing mutant HTT expression, since the HD mutation is considered to be a \"gain-of-function\" mutation. Allele-specific strategies that preserve expression from the wild-type allele and reduce the levels of mutant protein would be of particular interest. Here, we have conducted proof-of-concept studies to demonstrate that spliceosome-mediated trans-splicing is a viable molecular strategy to specifically repair the HTT allele. We employed a dual plasmid transfection system consisting of a pre-mRNA trans-splicing module (PTM) containing HTT exon 1 and a HTT minigene to demonstrate that HTT exon 1 can be replaced in trans. We detected the presence of the trans-spliced RNA in which PTM exon 1 was correctly joined to minigene exons 2 and 3. Furthermore, exon 1 from the PTM was trans-spliced to the endogenous HTT pre-mRNA in cultured cells as well as disease-relevant models, including HD patient fibroblasts and primary neurons from a previously described HD mouse model. These results suggest that the repeat expansion of HTT can be repaired successfully not only in the context of synthetic minigenes but also within the context of HD neurons. Therefore, pre-mRNA trans-splicing may be a promising approach for the treatment of HD and other dominant genetic disorders.",
+ "publisher": "Cellular and molecular neurobiology",
+ "issn": "0272-4340",
+ "date": "2007-10-20",
+ "abstract": "The mitochondrial DNA (mtDNA) may play an essential role in the pathogenesis of the respiratory chain complex activities in neurodegenerative disorders such as Huntington's disease (HD). Research studies were conducted to determine the possible levels of mitochondrial defect (deletion) in HD patients and consideration of interaction between the expanded Huntingtin gene as a nuclear gene and mitochondria as a cytoplasmic organelle. To determine mtDNA damage, we investigated deletions based in four areas of mitochondrial DNA, in a group of 60 Iranian patients clinically diagnosed with HD and 70 healthy controls. A total of 41 patients out of 60 had CAG expansion (group A). About 19 patients did not show expansion but had the clinical symptoms of HD (group B). MtDNA deletions were classified into four groups according to size; 9 kb, 7.5 kb, 7 kb, and 5 kb. We found one of the four-mtDNA deletions in at least 90% of samples. Multiple deletions have also been observed in 63% of HD patients. None of the normal control (group C) showed mtDNA deletions. The sizes or locations of the deletions did not show a clear correlation with expanded CAG repeat and age in our samples. The study presented evidence that HD patients had higher frequencies of mtDNA deletions in lymphocytes in comparison to the controls. It is thus proposed that CAG repeats instability and mutant Htt are causative factor in mtDNA damage.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22814437"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17952586"
},
{
- "id": "pmid:22803944",
+ "id": "pmid:17947312",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/22803944",
- "title": "Initiation of 8-oxoguanine base excision repair within trinucleotide tandem repeats.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17947312",
+ "title": "Corticostriatal synaptic function in mouse models of Huntington's disease: early effects of huntingtin repeat length and protein load.",
"type": "article-journal",
- "doi": "10.1134/s0006297912030054",
+ "doi": "10.1113/jphysiol.2007.142448",
"authors": [
- ["A G", "Derevyanko"],
- ["A V", "Endutkin"],
- ["A A", "Ishchenko"],
- ["M K", "Saparbaev"],
- ["D O", "Zharkov"]
+ ["Austen J", "Milnerwood"],
+ ["Lynn A", "Raymond"]
],
- "publisher": "Biochemistry. Biokhimiia",
- "issn": "1608-3040",
- "date": "2012-03-01",
- "abstract": "Trinucleotide repeat expansion provides a molecular basis for several devastating neurodegenerative diseases. In particular, expansion of a CAG run in the human HTT gene causes Huntington's disease. One of the main reasons for triplet repeat expansion in somatic cells is base excision repair (BER), involving damaged base excision and repair DNA synthesis that may be accompanied by expansion of the repaired strand due to formation of noncanonical DNA structures. We have analyzed the kinetics of excision of a ubiquitously found oxidized purine base, 8-oxoguanine (oxoG), by DNA glycosylase OGG1 from the substrates containing a CAG run flanked by AT-rich sequences. The values of k(2) rate constant for the removal of oxoG from triplets in the middle of the run were higher than for oxoG at the flanks of the run. The value of k(3) rate constant dropped starting from the third CAG-triplet in the run and remained stable until the 3'-terminal triplet, where it decreased even more. In nuclear extracts, the profile of oxoG removal rate along the run resembled the profile of k(2) constant, suggesting that the reaction rate in the extracts is limited by base excision. The fully reconstituted BER was efficient with all substrates unless oxoG was near the 3'-flank of the run, interfering with the initiation of the repair. DNA polymerase \u03b2 was able to perform a strand-displacement DNA synthesis, which may be important for CAG run expansion initiated by BER.",
+ "publisher": "The Journal of physiology",
+ "issn": "0022-3751",
+ "date": "2007-10-18",
+ "abstract": "Huntington's disease (HD) is an autosomal dominant, late onset, neurodegenerative disease characterized by motor deficits and dementia that is caused by expansion of a CAG repeat in the HD gene. Clinical manifestations result from selective neuronal degeneration of predominantly GABAergic striatal medium-sized spiny neurons (MSNs). A growing number of studies demonstrate that personality, mood and cognitive disturbances are some of the earliest signs of HD and may reflect synaptic dysfunction prior to neuronal loss. Previous studies in striatal MSNs demonstrated early alterations in NMDA-type glutamate receptor currents in several HD mouse models, as well as evidence for presynaptic dysfunction prior to disease manifestations in the R6/2 HD fragment mouse model. We have compared corticostriatal synaptic function in full-length, human HD gene-carrying YAC transgenic mice expressing a non-pathogenic CAG repeat (YAC18; control) with three increasingly severe variants of pathogenic HD gene-expressing mice (YAC72 and two different lines of YAC128), at ages that precede any detectable disease phenotype. We report presynaptic dysfunction and a propensity towards synaptic depression in YAC72 and YAC128 compared to YAC18 mice, and, in the most severe model, we also observed altered AMPA receptor function. When normalized to evoked AMPAR currents, postsynaptic NMDAR currents are augmented in all three pathogenic HD YAC variants. These findings demonstrate multiple perturbations to corticostriatal synaptic function in HD mice, furthering our understanding of the early effects of the HD mutation that may contribute to cognitive dysfunction, mood disorders and later development of more serious dysfunction. Furthermore, this study provides a set of neurophysiological sequelae against which to test and compare other mouse models and potential therapies in HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22803944"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17947312"
},
{
- "id": "pmid:22786682",
+ "id": "pmid:17726644",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/22786682",
- "title": "PGC-1\u03b1 rescues Huntington's disease proteotoxicity by preventing oxidative stress and promoting TFEB function.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17726644",
+ "title": "Glutamate uptake is reduced in prefrontal cortex in Huntington's disease.",
"type": "article-journal",
- "doi": "10.1126/scitranslmed.3003799",
+ "doi": "10.1007/s11064-007-9463-1",
"authors": [
- ["Taiji", "Tsunemi"],
- ["Travis D", "Ashe"],
- ["Bradley E", "Morrison"],
- ["Kathryn R", "Soriano"],
- ["Jonathan", "Au"],
- ["Ruben A V\u00e1zquez", "Roque"],
- ["Eduardo R", "Lazarowski"],
- ["Vincent A", "Damian"],
- ["Eliezer", "Masliah"],
- ["Albert R", "La Spada"]
+ ["Bj\u00f8rnar", "Hassel"],
+ ["Shoshi", "Tessler"],
+ ["Richard L M", "Faull"],
+ ["Piers C", "Emson"]
],
- "publisher": "Science translational medicine",
- "issn": "1946-6242",
- "date": "2012-07-11",
- "abstract": "Huntington's disease (HD) is caused by CAG repeat expansions in the huntingtin (htt) gene, yielding proteins containing polyglutamine repeats that become misfolded and resist degradation. Previous studies demonstrated that mutant htt interferes with transcriptional programs coordinated by the peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3) coactivator 1\u03b1 (PGC-1\u03b1), a regulator of mitochondrial biogenesis and oxidative stress. We tested whether restoration of PGC-1\u03b1 could ameliorate the symptoms of HD in a mouse model. We found that PGC-1\u03b1 induction virtually eliminated htt protein aggregation and ameliorated HD neurodegeneration in part by attenuating oxidative stress. PGC-1\u03b1 promoted htt turnover and the elimination of protein aggregates by activating transcription factor EB (TFEB), a master regulator of the autophagy-lysosome pathway. TFEB alone was capable of reducing htt aggregation and neurotoxicity, placing PGC-1\u03b1 upstream of TFEB and identifying these two molecules as important therapeutic targets in HD and potentially other neurodegenerative disorders caused by protein misfolding.",
+ "publisher": "Neurochemical research",
+ "issn": "0364-3190",
+ "date": "2007-08-29",
+ "abstract": "Huntington's disease (HD) is caused by a CAG repeat expansion in the HD gene, but how this mutation causes neuronal dysfunction and degeneration is unclear. Inhibition of glutamate uptake, which could cause excessive stimulation of glutamate receptors, has been found in animals carrying very long CAG repeats in the HD gene. In seven HD patients with moderate CAG expansions (40-52), repeat expansion and HD grade at autopsy were strongly correlated (r=0.88, p=0.0002). Uptake of [(3)H]glutamate was reduced by 43% in prefrontal cortex, but the level of synaptic (synaptophysin, AMPA receptors) and astrocytic markers (GFAP, glutamate transporter EAAT1) were unchanged. Glutamate uptake correlated inversely with CAG repeat expansion (r= -0.82, p=0.015). The reducing agent dithiothreitol improved glutamate uptake in controls, but not in HD brains, suggesting irreversible oxidation of glutamate transporters in HD. We conclude that impairment of glutamate uptake may contribute to neuronal dysfunction and degeneration in HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22786682"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17726644"
},
{
- "id": "pmid:22668780",
+ "id": "pmid:17660463",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/22668780",
- "title": "Mitigation of augmented extrasynaptic NMDAR signaling and apoptosis in cortico-striatal co-cultures from Huntington's disease mice.",
- "type": "article-journal",
- "doi": "10.1016/j.nbd.2012.05.013",
- "authors": [
- ["Austen J", "Milnerwood"],
- ["Alexandra M", "Kaufman"],
- ["Marja D", "Sepers"],
- ["Clare M", "Gladding"],
- ["Lily", "Zhang"],
- ["Liang", "Wang"],
- ["Jing", "Fan"],
- ["Ainsley", "Coquinco"],
- ["Joy Yi", "Qiao"],
- ["Hwan", "Lee"],
- ["Yu Tian", "Wang"],
- ["Max", "Cynader"],
- ["Lynn A", "Raymond"]
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17660463",
+ "title": "Factors associated with HD CAG repeat instability in Huntington disease.",
+ "type": "article-journal",
+ "doi": "10.1136/jmg.2007.050930",
+ "authors": [
+ ["V C", "Wheeler"],
+ ["F", "Persichetti"],
+ ["S M", "McNeil"],
+ ["J S", "Mysore"],
+ ["S S", "Mysore"],
+ ["M E", "MacDonald"],
+ ["R H", "Myers"],
+ ["J F", "Gusella"],
+ ["N S", "Wexler"]
],
- "publisher": "Neurobiology of disease",
- "issn": "1095-953X",
- "date": "2012-06-02",
- "abstract": "We recently reported evidence for disturbed synaptic versus extrasynaptic NMDAR transmission in the early pathogenesis of Huntington's disease (HD), a late-onset neurodegenerative disorder caused by CAG repeat expansion in the gene encoding huntingtin. Studies in glutamatergic cells indicate that synaptic NMDAR transmission increases phosphorylated cyclic-AMP response element binding protein (pCREB) levels and drives neuroprotective gene transcription, whereas extrasynaptic NMDAR activation reduces pCREB and promotes cell death. By generating striatal and cortical neuronal co-cultures to investigate the glutamatergic innervation of striatal neurons, we demonstrate that dichotomous synaptic and extrasynaptic NMDAR signaling also occurs in GABAergic striatal medium-sized spiny neurons (MSNs), which are acutely vulnerable in HD. Further, we show that wild-type (WT) and HD transgenic YAC128 MSNs co-cultured with cortical cells have similar levels of glutamatergic synapses, synaptic NMDAR currents and synaptic GluN2B and GluN2A subunit-containing NMDARs. However, NMDAR whole-cell, and especially extrasynaptic, current is elevated in YAC128 MSNs. Moreover, GluN2B subunit-containing NMDAR surface expression is markedly increased, irrespective of whether or not the co-cultured cortical cells express mutant huntingtin. The data suggest that MSN cell-autonomous increases in extrasynaptic NMDARs are driven by the HD mutation. Consistent with these results, we find that extrasynaptic NMDAR-induced pCREB reductions and apoptosis are also augmented in YAC128 MSNs. Moreover, both NMDAR-mediated apoptosis and CREB-off signaling are blocked by co-application of either memantine or the GluN2B subunit-selective antagonist ifenprodil in YAC128 MSNs. GluN2A-subunit-selective concentrations of the antagonist NVP-AAM077 did not reduce cell death in either genotype. Cortico-striatal co-cultures provide an in vitro model system in which to better investigate striatal neuronal dysfunction in disease than mono-cultured striatal cells. Results from the use of this system, which partially recapitulates the cortico-striatal circuit and is amenable to acute genetic and pharmacological manipulations, suggest that pathophysiological NMDAR signaling is an intrinsic frailty in HD MSNs that can be successfully targeted by pharmacological interventions.",
+ "publisher": "Journal of medical genetics",
+ "issn": "1468-6244",
+ "date": "2007-07-27",
+ "abstract": "The Huntington disease (HD) CAG repeat exhibits dramatic instability when transmitted to subsequent generations. The instability of the HD disease allele in male intergenerational transmissions is reflected in the variability of the CAG repeat in DNA from the sperm of male carriers of the HD gene.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22668780"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17660463"
},
{
- "id": "pmid:22649062",
+ "id": "pmid:17653603",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/22649062",
- "title": "Brain metabolite alterations and cognitive dysfunction in early Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17653603",
+ "title": "Survival of Huntington's disease patients in Serbia: longer survival in female patients.",
"type": "article-journal",
- "doi": "10.1002/mds.25010",
+ "doi": "10.1007/s10654-007-9157-7",
"authors": [
- ["Paul G", "Unschuld"],
- ["Richard A E", "Edden"],
- ["Aaron", "Carass"],
- ["Xinyang", "Liu"],
- ["Megan", "Shanahan"],
- ["Xin", "Wang"],
- ["Kenichi", "Oishi"],
- ["Jason", "Brandt"],
- ["Susan S", "Bassett"],
- ["Graham W", "Redgrave"],
- ["Russell L", "Margolis"],
- ["Peter C M", "van Zijl"],
- ["Peter B", "Barker"],
- ["Christopher A", "Ross"]
+ ["Tatjana", "Pekmezovic"],
+ ["Marina", "Svetel"],
+ ["Jelena", "Maric"],
+ ["Irena", "Dujmovic-Basuroski"],
+ ["Natasa", "Dragasevic"],
+ ["Milica", "Keckarevic"],
+ ["Stanka", "Romac"],
+ ["Vladimir S", "Kostic"]
],
- "publisher": "Movement disorders : official journal of the Movement Disorder Society",
- "issn": "1531-8257",
- "date": "2012-05-30",
- "abstract": "Huntington's disease (HD) is a neurodegenerative disorder characterized by early cognitive decline that progresses at later stages to dementia and severe movement disorder. HD is caused by a cytosine-adenine-guanine triplet-repeat expansion mutation in the Huntingtin gene, allowing early diagnosis by genetic testing. This study aimed to identify the relationship of N-acetylaspartate and other brain metabolites to cognitive function in HD-mutation carriers by using high-field-strength magnetic resonance spectroscopy (MRS) at 7 Tesla. Twelve individuals with the HD mutation in premanifest or early-stage disease versus 12 healthy controls underwent (1)H magnetic resonance spectroscopy (7.2 mL voxel in the posterior cingulate cortex) at 7 Tesla, and also T1-weighted structural magnetic resonance imaging. All participants received standardized tests of cognitive functioning including the Montreal Cognitive Assessment and standardized quantified neurological examination within an hour before scanning. Individuals with the HD mutation had significantly lower posterior cingulate cortex N-acetylaspartate (-9.6%, P = .02) and glutamate (-10.1%, P = .02) levels than did controls. In contrast, in this small group, measures of brain morphology including striatal and ventricle volumes did not differ significantly. Linear regression with Montreal Cognitive Assessment scores revealed significant correlations with N-acetylaspartate (r(2) = 0.50, P = .01) and glutamate (NAA) (r(2) = 0.64, P = .002) in HD subjects. Our data suggest a relationship between reduced N-acetylaspartate and glutamate levels in the posterior cingulate cortex with cognitive decline in the early stages of HD. N-acetylaspartate and glutamate magnetic resonance spectroscopy signals of the posterior cingulate cortex region may serve as potential biomarkers of disease progression or treatment outcome in HD and other neurodegenerative disorders with early cognitive dysfunction, when structural brain changes are still minor.",
+ "publisher": "European journal of epidemiology",
+ "issn": "0393-2990",
+ "date": "2007-07-25",
+ "abstract": "The objective of this study was to estimate probability of survival of Huntington's disease (HD) patients in Serbia as a function of CAG repeat length and selected demographic variables. This follow-up study was carried out at the Institute of Neurology, Clinical Centre of Serbia, Belgrade, 1982-2004. The study group consisted of 112 HD patients. The significant inverse correlation was found between CAG repeat length and age at onset of HD (r = -0.732, P = 0.001) and age at death (r = -0.760, P = 0.001). The cumulative probabilities of survival in a five, ten, fifteen, and twenty-years' period were 90.9, 63.2, 10.3 and 4.5%, respectively. Higher survival probabilities were registered in female patients, as well as in those with older age at onset and lower number of CAG repeat length ( or = Vonsattel et al's grade I, five patients lacking striatal tissue for review, and two at-risk individuals with grade 0 and grade I HD pathology, respectively. One patient with HD-like pathology and two patients and four at-risk individuals without HD pathology lacked HD inclusions. In the genetically analyzed cases, the inclusions were exclusively and consistently observed in association with repeat expansion [(CAG)(n) > or = 39, n = 81]. Thirteen inclusion-positive cases, including the grade 0 at-risk individual, had a false negative original pathological diagnosis of HD and four had an unjustly questionable diagnosis. A false positive diagnosis was made in the inclusion-negative case with HD-like pathology. These results indicate that immunohistochemical analysis for HD inclusions facilitates the pathological evaluation of HD and enhances its accuracy.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22454241"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17493035"
},
{
- "id": "pmid:22425717",
+ "id": "pmid:17478887",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/22425717",
- "title": "Impaired cortico-striatal functional connectivity in prodromal Huntington's Disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17478887",
+ "title": "Decreased VIP and VPAC2 receptor expression in the biological clock of the R6/2 Huntington's disease mouse.",
"type": "article-journal",
- "doi": "10.1016/j.neulet.2012.02.095",
+ "doi": "10.1385/jmn/31:02:139",
"authors": [
- ["Paul G", "Unschuld"],
- ["Suresh E", "Joel"],
- ["Xinyang", "Liu"],
- ["Megan", "Shanahan"],
- ["Russell L", "Margolis"],
- ["Kevin M", "Biglan"],
- ["Susan S", "Bassett"],
- ["David J", "Schretlen"],
- ["Graham W", "Redgrave"],
- ["Peter C M", "van Zijl"],
- ["James J", "Pekar"],
- ["Christopher A", "Ross"]
+ ["Jan", "Fahrenkrug"],
+ ["Natalija", "Popovic"],
+ ["Birgitte", "Georg"],
+ ["Patrik", "Brundin"],
+ ["Jens", "Hannibal"]
],
- "publisher": "Neuroscience letters",
- "issn": "1872-7972",
- "date": "2012-03-07",
- "abstract": "Huntington's Disease (HD) is a neurodegenerative disease caused by a CAG triplet-repeat expansion-mutation in the Huntingtin gene. Subjects at risk for HD can be identified by genetic testing in the prodromal phase. Structural changes of basal-ganglia nuclei such as the caudate nucleus are well-replicated findings observable early in prodromal-HD subjects and may be preceded by distinct functional alterations of cortico-striatal circuits. This study aims to assess functional integrity of the motor system as a cortico-striatal circuit with particular clinical relevance in HD. Ten subjects in the prodromal phase of HD and ten matched controls were administered blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) at rest (3T). Functional connectivity was measured as synchrony of BOLD activity between the caudate nucleus and thirteen cortical brain regions (seeds). Basal-ganglia volumes were assessed as established markers of disease progression in prodromal-HD. Linear regression analysis was performed to test for a relationship between structural changes and group differences in functional connectivity. Prodromal-HD subjects showed reduced BOLD synchrony between two seeds in the premotor cortex (BA6) and the caudate nucleus. While similar effect sizes could be observed for reduced basal-ganglia volumes and differences in functional connectivity, coefficients of determination indicate a moderate relationship between functional connectivity and striatal atrophy. Our data show reduced cortico-striatal functional connectivity at rest in prodromal-HD and suggest a relation to early structural brain changes. Additional longitudinal studies are necessary to elucidate the temporal relationship between functional alterations and earliest structural brain changes in prodromal-HD.",
+ "publisher": "Journal of molecular neuroscience : MN",
+ "issn": "0895-8696",
+ "date": "2007-01-01",
+ "abstract": "Huntington's disease (HD) is a fatal genetic neurodegenerative disorder caused by a CAG triplet repeat expansion in the gene encoding the protein huntingtin. The most studied model of HD, the R6/2 transgenic mouse, replicates many features of the disease. In addition to motor, cognitive, and endocrine dysfunctions, these mice exhibit a progressive disruption of circadian rhythms. This is accompanied by an altered expression of the circadian clock genes in the suprachiasmatic nucleus/nuclei (SCN), the principal circadian pacemaker in the brain. The neuropeptide vasoactive intestinal polypeptide (VIP) and its receptor VPAC2 are highly expressed in the SCN, and VIPergic signaling plays an essential role in maintenance of ongoing circadian rhythmicity. We found a marked reduction in both VIP mRNA and VPAC2 receptor mRNA, quantified by RT-PCR, as well as a decrease in VIP immunostaining in the SCN of R6/2 mice. These changes were coupled to a disruption of circadian rhythm. We observed no loss of neurons in the SCN and therefore suggest that the changes in VIP and VPAC2 receptor are due to their decreased expression. In conclusion, we propose that impaired VIPergic signaling is an additional candidate mechanism for disruption of circadian rhythms in R6/2 mice.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22425717"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17478887"
},
{
- "id": "pmid:22383888",
+ "id": "pmid:17383831",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/22383888",
- "title": "A pathogenic mechanism in Huntington's disease involves small CAG-repeated RNAs with neurotoxic activity.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17383831",
+ "title": "Haploinsufficiency of yeast FEN1 causes instability of expanded CAG/CTG tracts in a length-dependent manner.",
"type": "article-journal",
- "doi": "10.1371/journal.pgen.1002481",
+ "doi": "10.1016/j.gene.2007.01.025",
"authors": [
- ["M\u00f3nica", "Ba\u00f1ez-Coronel"],
- ["Silvia", "Porta"],
- ["Birgit", "Kagerbauer"],
- ["Elisabet", "Mateu-Huertas"],
- ["Lorena", "Pantano"],
- ["Isidre", "Ferrer"],
- ["Manuel", "Guzm\u00e1n"],
- ["Xavier", "Estivill"],
- ["Eul\u00e0lia", "Mart\u00ed"]
+ ["Jiahui", "Yang"],
+ ["Catherine H", "Freudenreich"]
],
- "publisher": "PLoS genetics",
- "issn": "1553-7404",
- "date": "2012-02-23",
- "abstract": "Huntington's disease (HD) is an autosomal dominantly inherited disorder caused by the expansion of CAG repeats in the Huntingtin (HTT) gene. The abnormally extended polyglutamine in the HTT protein encoded by the CAG repeats has toxic effects. Here, we provide evidence to support that the mutant HTT CAG repeats interfere with cell viability at the RNA level. In human neuronal cells, expanded HTT exon-1 mRNA with CAG repeat lengths above the threshold for complete penetrance (40 or greater) induced cell death and increased levels of small CAG-repeated RNAs (sCAGs), of \u224821 nucleotides in a Dicer-dependent manner. The severity of the toxic effect of HTT mRNA and sCAG generation correlated with CAG expansion length. Small RNAs obtained from cells expressing mutant HTT and from HD human brains significantly decreased neuronal viability, in an Ago2-dependent mechanism. In both cases, the use of anti-miRs specific for sCAGs efficiently blocked the toxic effect, supporting a key role of sCAGs in HTT-mediated toxicity. Luciferase-reporter assays showed that expanded HTT silences the expression of CTG-containing genes that are down-regulated in HD. These results suggest a possible link between HD and sCAG expression with an aberrant activation of the siRNA/miRNA gene silencing machinery, which may trigger a detrimental response. The identification of the specific cellular processes affected by sCAGs may provide insights into the pathogenic mechanisms underlying HD, offering opportunities to develop new therapeutic approaches.",
+ "publisher": "Gene",
+ "issn": "0378-1119",
+ "date": "2007-02-12",
+ "abstract": "Trinucleotide repeat diseases, such as Huntington's disease, are caused by the expansion of trinucleotide repeats above a threshold of about 35 repeats. Once expanded, the repeats are unstable and tend to expand further both in somatic cells and during transmission, resulting in a more severe disease phenotype. Flap endonuclease 1 (Fen1), has an endonuclease activity specific for 5' flap structures and is involved in Okazaki fragment processing and base excision repair. Fen1 also plays an important role in preventing instability of CAG/CTG trinucleotide repeat sequences, as the expansion frequency of CAG/CTG repeats is increased in FEN1 mutants in vitro and in yeast cells defective for the yeast homolog, RAD27. Here we have tested whether one copy of yeast FEN1 is enough to maintain CAG/CTG tract stability in diploid yeast cells. We found that CAG/CTG repeats are stable in RAD27 +/- cells if the tract is 70 repeats long and exhibit a slightly increased expansion frequency if the tract is 85 or 130 repeats long. However for CAG-155 tracts, the repeat expansion frequency in RAD27 +/- cells is significantly higher than in RAD27 +/+ cells. This data indicates that cells containing longer CAG/CTG repeats need more Fen1 protein to maintain tract stability and that maintenance of long CAG/CTG repeats is particularly sensitive to Fen1 levels. Our results may explain the relatively small effects seen in the Huntington's disease (HD) FEN1 +/- heterozygous mice and myotonic dystrophy type 1 (DM1) FEN1 +/- heterozygous mice, and suggest that inefficient flap processing by Fen1 could play a role in the continued expansions seen in humans with trinucleotide repeat expansion diseases.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22383888"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17383831"
},
{
- "id": "pmid:22367996",
+ "id": "pmid:17363167",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/22367996",
- "title": "Loss of junctophilin-3 contributes to Huntington disease-like 2 pathogenesis.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17363167",
+ "title": "Plasma neurofilament heavy chain levels in Huntington's disease.",
"type": "article-journal",
- "doi": "10.1002/ana.22598",
+ "doi": "10.1016/j.neulet.2007.02.053",
"authors": [
- ["Ana I", "Seixas"],
- ["Susan E", "Holmes"],
- ["Hiroshi", "Takeshima"],
- ["Amira", "Pavlovich"],
- ["Nancy", "Sachs"],
- ["Jennifer L", "Pruitt"],
- ["Isabel", "Silveira"],
- ["Christopher A", "Ross"],
- ["Russell L", "Margolis"],
- ["Dobrila D", "Rudnicki"]
+ ["Edward J", "Wild"],
+ ["Axel", "Petzold"],
+ ["Geoff", "Keir"],
+ ["Sarah J", "Tabrizi"]
],
- "publisher": "Annals of neurology",
- "issn": "1531-8249",
- "date": "2012-02-01",
- "abstract": "Huntington disease-like 2 (HDL2) is a progressive, late onset autosomal dominant neurodegenerative disorder, with remarkable similarities to Huntington disease (HD). HDL2 is caused by a CTG/CAG repeat expansion. In the CTG orientation, the repeat is located within the alternatively spliced exon 2A of junctophilin-3 (JPH3), potentially encoding polyleucine and polyalanine, whereas on the strand antisense to JPH3, the repeat is in frame to encode polyglutamine. The JPH3 protein product serves to stabilize junctional membrane complexes and regulate neuronal calcium flux. We have previously demonstrated the potential pathogenic properties of JPH3 transcripts containing expanded CUG repeats. The aim of this study was to test the possibility that loss of JPH3 expression or expanded amino acid tracts also contribute to HDL2 pathogenesis.",
+ "publisher": "Neuroscience letters",
+ "issn": "0304-3940",
+ "date": "2007-02-24",
+ "abstract": "There is a need for biomarkers of onset and progression in Huntington's disease (HD), as current outcome measures lack the reliability to enable the efficient conduct of disease-modifying trials. Neurofilament heavy chain (NfH) is a neuron-specific protein for the neuro-axonal compartment that has been proposed as a marker for axonal injury, degeneration and loss and its clinical use as a biomarker has been suggested in several neurodegenerative diseases. We used an enzyme-linked immunosorbent assay to quantify NfH levels in plasma in control subjects, premanifest HD mutation carriers and subjects with early and moderate manifest HD. We found no correlation between plasma NfH level and disease stage, or calculated parameters based on CAG repeat length, the major determinant of disease course in HD, and no evidence that NfH may be a predictor of disease onset. We conclude that plasma NfH concentration is not a useful biomarker of onset or progression in HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22367996"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17363167"
},
{
- "id": "pmid:22359536",
+ "id": "pmid:17356014",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/22359536",
- "title": "Characterization of a large group of individuals with huntington disease and their relatives enrolled in the COHORT study.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17356014",
+ "title": "Extended polyglutamine repeats trigger a feedback loop involving the mitochondrial complex III, the proteasome and huntingtin aggregates.",
"type": "article-journal",
- "doi": "10.1371/journal.pone.0029522",
+ "doi": "10.1093/hmg/ddm023",
"authors": [
- ["E Ray", "Dorsey"]
+ ["Hirokazu", "Fukui"],
+ ["Carlos T", "Moraes"]
],
- "publisher": "PloS one",
- "issn": "1932-6203",
- "date": "2012-02-16",
- "abstract": "Careful characterization of the phenotype and genotype of Huntington disease (HD) can foster better understanding of the condition.",
+ "publisher": "Human molecular genetics",
+ "issn": "0964-6906",
+ "date": "2007-03-13",
+ "abstract": "Mitochondrial abnormalities represent a major cytopathology in Huntington's disease (HD), a fatal neurodegenerative disease caused by CAG repeat expansions in the gene encoding huntingtin (Htt). In the present study, we investigated whether defects in the mitochondrial respiratory function are consequences of the expression of mutant Htt or they promote the formation of Htt aggregates. To take advantage of existing mitochondrial DNA mutants, we developed human osteosarcoma 143B cells expressing mutant Htt in an inducible manner and found that cells expressing mutant Htt but not wild-type Htt exhibited a reduced activity of complex III and an increased activity of complex IV. Conversely, pharmacological treatments that inhibited complex III activity significantly promoted the formation of Htt aggregates. This complex III-mediated modulation of Htt aggregates was also observed in a neuronal progenitor RN33B cell line transduced by lentivirus carrying mutant Htt. This effect of complex III inhibition on the Htt aggregates appeared to be mediated by the inhibition of proteasome activity, but not by ATP depletion or production of reactive oxygen species. Accordingly, complex III mutant cells also showed decreased proteasome activity. These results suggest the presence of a feedback system connecting the mitochondrial respiratory complex III and the production of Htt aggregates. Our results suggest that therapeutic interventions targeting complex III and/or proteasome could ameliorate the progress of HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22359536"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17356014"
},
{
- "id": "pmid:22237433",
+ "id": "pmid:17352930",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/22237433",
- "title": "Assessing the analytic validity of molecular testing for Huntington disease using data from an external proficiency testing survey.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17352930",
+ "title": "Genetic criteria for Huntington's disease pathogenesis.",
"type": "article-journal",
- "doi": "10.1038/gim.0b013e3182310bb5",
+ "doi": "10.1016/j.brainresbull.2006.10.014",
"authors": [
- ["Glenn E", "Palomaki"],
- ["C Sue", "Richards"]
+ ["James F", "Gusella"],
+ ["Marcy", "Macdonald"]
],
- "publisher": "Genetics in medicine : official journal of the American College of Medical Genetics",
- "issn": "1530-0366",
- "date": "2011-09-26",
- "abstract": "Documenting high analytic validity of the molecular diagnostic test for Huntington disease is important because of counseling implications. This dominantly inherited adult onset disorder (prevalence of three or more per 100,000) is characterized by chorea, ataxia, and personality changes. The molecular basis is excessive CAG repeats in the HTT gene.",
+ "publisher": "Brain research bulletin",
+ "issn": "0361-9230",
+ "date": "2006-11-15",
+ "abstract": "Genetic analysis aims to identify the variations in DNA sequence whose functional consequences produce heritable variations in phenotype. In one of the first successes of unbiased molecular genetic analysis in human disease, the Huntington's disease (HD) gene was mapped and cloned without any prior knowledge of the nature of its protein product or of the molecular defect that underlies the characteristic phenotype of the disorder. However, while the cloning of HD and recognition of its trinucleotide repeat expansion spawned a plethora of approaches to investigating HD through its distinctive neuropathology, the role for genetic strategies in HD research did not end there. The use of genetic analysis has remained a critical tool for defining the characteristics of the mechanism that triggers the pathogenic process, permitting the investigation of early events that occur long before traditionally recognized pathology. Delineation of these events can reveal molecular targets for development of therapies that prevent onset of HD. Most recently, an extension of genetic analysis to the identification of non-linked genetic variations that alter the course of HD pathogenesis has offered the promise of identifying modifier genes to reveal biological pathways active throughout the disease process and to provide valid targets for pharmacological intervention. Thus, unbiased genetic strategies have not only provided a crucial entr\u00e9e into molecular investigation of HD via a root cause that was previously unsuspected, they also represent a continuing route to accelerate the ultimate goal of developing an effective treatment for HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22237433"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17352930"
},
{
- "id": "pmid:22235343",
+ "id": "pmid:17307423",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/22235343",
- "title": "Variation within the Huntington's disease gene influences normal brain structure.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17307423",
+ "title": "Repeat length polymorphism of the serotonin transporter gene influences pulmonary artery pressure in heart failure.",
"type": "article-journal",
- "doi": "10.1371/journal.pone.0029809",
+ "doi": "10.1016/j.ahj.2006.12.011",
"authors": [
- ["Mark", "M\u00fchlau"],
- ["Juliane", "Winkelmann"],
- ["Dan", "Rujescu"],
- ["Ina", "Giegling"],
- ["Nikolaos", "Koutsouleris"],
- ["Christian", "Gaser"],
- ["Milan", "Arsic"],
- ["Adolph", "Weindl"],
- ["Maximilian", "Reiser"],
- ["Eva M", "Meisenzahl"]
+ ["Thomas P", "Olson"],
+ ["Eric M", "Snyder"],
+ ["Robert P", "Frantz"],
+ ["Stephen T", "Turner"],
+ ["Bruce D", "Johnson"]
],
- "publisher": "PloS one",
- "issn": "1932-6203",
- "date": "2012-01-03",
- "abstract": "Genetics of the variability of normal and diseased brain structure largely remains to be elucidated. Expansions of certain trinucleotide repeats cause neurodegenerative disorders of which Huntington's disease constitutes the most common example. Here, we test the hypothesis that variation within the IT15 gene on chromosome 4, whose expansion causes Huntington's disease, influences normal human brain structure. In 278 normal subjects, we determined CAG repeat length within the IT15 gene on chromosome 4 and analyzed high-resolution T1-weighted magnetic resonance images by the use of voxel-based morphometry. We found an increase of GM with increasing long CAG repeat and its interaction with age within the pallidum, which is involved in Huntington's disease. Our study demonstrates that a certain trinucleotide repeat influences normal brain structure in humans. This result may have important implications for the understanding of both the healthy and diseased brain.",
+ "publisher": "American heart journal",
+ "issn": "1097-6744",
+ "date": "2007-03-01",
+ "abstract": "Pulmonary hypertension is common in patients with heart failure (HF); however, for a given degree of left ventricular dysfunction, the range in pulmonary artery pressures (PAPs) is large. Polymorphisms of the serotonin transporter (5-HTT) gene have been implicated in contributing to smooth muscle dysfunction and remodeling of the pulmonary vasculature. This study examined the influence of a repeat length polymorphism in the promoter region of the 5-HTT gene on PAP between patients with HF and healthy control participants.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22235343"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17307423"
},
{
- "id": "pmid:22219281",
+ "id": "pmid:17299512",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/22219281",
- "title": "Transgenic mouse model expressing the caspase 6 fragment of mutant huntingtin.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17299512",
+ "title": "Monoamine metabolites level in CSF is related to the 5-HTT gene polymorphism in treatment-resistant depression.",
"type": "article-journal",
- "doi": "10.1523/jneurosci.1305-11.2012",
+ "doi": "10.1038/sj.npp.1301336",
"authors": [
- ["Elaine", "Waldron-Roby"],
- ["Tamara", "Ratovitski"],
- ["XiaoFang", "Wang"],
- ["Mali", "Jiang"],
- ["Erin", "Watkin"],
- ["Nikolas", "Arbez"],
- ["Rona K", "Graham"],
- ["Michael R", "Hayden"],
- ["Zhipeng", "Hou"],
- ["Susumu", "Mori"],
- ["Deborah", "Swing"],
- ["Mikhail", "Pletnikov"],
- ["Wenzhen", "Duan"],
- ["Lino", "Tessarollo"],
- ["Christopher A", "Ross"]
+ ["Ikuko", "Kishida"],
+ ["Eleni", "Aklillu"],
+ ["Chiaki", "Kawanishi"],
+ ["Leif", "Bertilsson"],
+ ["Hans", "Agren"]
],
- "publisher": "The Journal of neuroscience : the official journal of the Society for Neuroscience",
- "issn": "1529-2401",
- "date": "2012-01-04",
- "abstract": "Huntington's disease (HD) is caused by a polyglutamine expansion in the Huntingtin (Htt) protein. Proteolytic cleavage of Htt into toxic N-terminal fragments is believed to be a key aspect of pathogenesis. The best characterized putative cleavage event is at amino acid 586, hypothesized to be mediated by caspase 6. A corollary of the caspase 6 cleavage hypothesis is that the caspase 6 fragment should be a toxic fragment. To test this hypothesis, and further characterize the role of this fragment, we have generated transgenic mice expressing the N-terminal 586 aa of Htt with a polyglutamine repeat length of 82 (N586-82Q), under the control of the prion promoter. N586-82Q mice show a clear progressive rotarod deficit by 4 months of age, and are hyperactive starting at 5 months, later changing to hypoactivity before early mortality. MRI studies reveal widespread brain atrophy, and histologic studies demonstrate an abundance of Htt aggregates, mostly cytoplasmic, which are predominantly composed of the N586-82Q polypeptide. Smaller soluble N-terminal fragments appear to accumulate over time, peaking at 4 months, and are predominantly found in the nuclear fraction. This model appears to have a phenotype more severe than current full-length Htt models, but less severe than HD mouse models expressing shorter Htt fragments. These studies suggest that the caspase 6 fragment may be a transient intermediate, that fragment size is a factor contributing to the rate of disease progression, and that short soluble nuclear fragments may be most relevant to pathogenesis.",
+ "publisher": "Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology",
+ "issn": "0893-133X",
+ "date": "2007-02-14",
+ "abstract": "The serotonin (5-hydroxytryptamine) transporter (5-HTT) is considered to affect the pathogenesis of mood disorders. Large number of genetic association studies between 5-HTT functional polymorphisms and vulnerability of mood disorders and therapeutic response to antidepressants has been carried out. We investigated the influence of 5-HTT-linked polymorphic region (5-HTTLPR) and 5-HTT 17 bp variable number of tandem repeat polymorphism (5-HTTVNTR) polymorphisms on concentrations of monoamine metabolites in cerebrospinal fluid (CSF) among treatment-resistant patients with mood disorders. Subjects were 119 Swedish patients with persistent mood disorders and 141 healthy subjects. In 112 of these patients, we measured 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol in CSF. Genotyping for 5-HTT polymorphisms from genomic DNA was carried out by PCR. There was no significant difference in allele/genotype frequency between patients and healthy subjects. In patients with mood disorders, we found significant difference in mean 5-HIAA concentration between 5-HTTLPR genotypes (p=0.03). Although the 5-HIAA concentration showed a tendency to be higher in short (S) carriers than in non-S carriers of the 5-HTTLPR in patients (p=0.06), when considering patients with major depressive disorder (MDD), the 5-HIAA concentration was significantly higher among S carriers than among non-S carriers (p=0.02). Moreover, the 5-HIAA concentration was higher in S/S subjects compared to long (L)/L (p=0.0001) and L/S (p=0.002) subjects in patients with MDD. Similarly, there was higher HVA concentration in S/S subjects compared to L/L (p=0.002) and L/S subjects (p=0.002). There was no effect of 5-HTTVNTR. Our findings show that the 5-HTTLPR polymorphism affects 5-HIAA and HVA concentrations among treatment-resistant patients with mood disorders.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22219281"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17299512"
},
{
- "id": "pmid:23925262",
+ "id": "pmid:17181545",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23925262",
- "title": "A mixed fixed ratio/progressive ratio procedure reveals an apathy phenotype in the BAC HD and the z_Q175 KI mouse models of Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17181545",
+ "title": "The relationship between CAG repeat length and age of onset differs for Huntington's disease patients with juvenile onset or adult onset.",
"type": "article-journal",
- "doi": "10.1371/4f972cffe82c0",
+ "doi": "10.1111/j.1469-1809.2006.00335.x",
"authors": [
- ["Stephen", "Oakeshott"],
- ["Russell", "Port"],
- ["Jane", "Cummins-Sutphen"],
- ["Jason", "Berger"],
- ["Judy", "Watson-Johnson"],
- ["Sylvie", "Ramboz"],
- ["Neil", "Paterson"],
- ["Seung", "Kwak"],
- ["David", "Howland"],
- ["Dani", "Brunner"]
+ ["J Michael", "Andresen"],
+ ["Javier", "Gay\u00e1n"],
+ ["Luc", "Djouss\u00e9"],
+ ["Simone", "Roberts"],
+ ["Denise", "Brocklebank"],
+ ["Stacey S", "Cherny"],
+ ["Lon R", "Cardon"],
+ ["James F", "Gusella"],
+ ["Marcy E", "MacDonald"],
+ ["Richard H", "Myers"],
+ ["David E", "Housman"],
+ ["Nancy S", "Wexler"]
],
- "publisher": "PLoS currents",
- "issn": "2157-3999",
- "date": "2012-04-25",
- "abstract": "Apathy, characterized by generally reduced interest in and likelihood to perform goal-directed actions, is a recognized symptom of Huntington's disease (HD), a devastating neurological disorder caused by a CAG repeat expansion of the Htt gene located on chromosome 4. The present experiments used a modified progressive ratio task that incorporated a fixed-ratio schedule of reinforcement component to assess consummatory behavior, and a progressive-ratio schedule component that required increasing numbers of lever-presses for successive reinforcers (0.01 ml of evaporated milk). The studies revealed an apathetic phenotype in two mouse models of HD, with decreased response rates either overall or only at higher ratio requirements in the progressive-ratio component relative to wild-type controls. Based on the procedure used (within-session fixed- and progressive-ratio components), it is proposed that an observed phenotype can be ascribed either specifically to reduced motivation to work for food reinforcement or more generally to deficits in consummatory behavior. This procedure provides a simple means to assess this type of phenotype in rodents, with issues in consummatory vs. incentive motivation reflected in general alterations in fixed- versus progressive alterations on an escalating-ratio schedules respectively, providing translational measures of the amotivation/apathy construct of the human realm to the homologous construct of incentive motivation in preclinical models of human disease.",
+ "publisher": "Annals of human genetics",
+ "issn": "0003-4800",
+ "date": "2006-12-19",
+ "abstract": "Age of onset for Huntington's disease (HD) varies inversely with the length of the disease-causing CAG repeat expansion in the HD gene. A simple exponential regression model yielded adjusted R-squared values of 0.728 in a large set of Venezuelan kindreds and 0.642 in a North American, European, and Australian sample (the HD MAPS cohort). We present evidence that a two-segment exponential regression curve provides a significantly better fit than the simple exponential regression. A plot of natural log-transformed age of onset against CAG repeat length reveals this segmental relationship. This two-segment exponential regression on age of onset data increases the adjusted R-squared values by 0.012 in the Venezuelan kindreds and by 0.035 in the HD MAPS cohort. Although the amount of additional variance explained by the segmental regression approach is modest, the two slopes of the two-segment regression are significantly different from each other in both the Venezuelan kindreds [F(2, 439) = 11.13, P= 2 x 10(-5)] and in the HD MAPS cohort [F(2, 688) = 38.27, P= 2 x 10(-16)]. In both populations, the influence of each CAG repeat on age of onset appears to be stronger in the adult-onset range of CAG repeats than in the juvenile-onset range.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23925262"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17181545"
},
{
- "id": "pmid:23476655",
+ "id": "pmid:17174018",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23476655",
- "title": "Predicting Disease Onset from Mutation Status Using Proband and Relative Data with Applications to Huntington's Disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17174018",
+ "title": "Association between obsessive-compulsive disorder and a variable number of tandem repeats polymorphism in intron 2 of the serotonin transporter gene.",
"type": "article-journal",
- "doi": "10.1155/2012/375935",
+ "doi": "10.1016/j.pnpbp.2006.10.016",
"authors": [
- ["Tianle", "Chen"],
- ["Yuanjia", "Wang"],
- ["Yanyuan", "Ma"],
- ["Karen", "Marder"],
- ["Douglas R", "Langbehn"]
+ ["Enrique", "Baca-Garcia"],
+ ["Concepcion", "Vaquero-Lorenzo"],
+ ["Montserrat", "Diaz-Hernandez"],
+ ["Beatriz", "Rodriguez-Salgado"],
+ ["Helen", "Dolengevich-Segal"],
+ ["Manuel", "Arrojo-Romero"],
+ ["Carlota", "Botillo-Martin"],
+ ["Antonio", "Ceverino"],
+ ["Jose Fernandez", "Piqueras"],
+ ["M Mercedes", "Perez-Rodriguez"],
+ ["Jeronimo", "Saiz-Ruiz"]
],
- "publisher": "Journal of probability and statistics",
- "issn": "1687-952X",
- "date": "2012-01-01",
- "abstract": "Huntington's disease (HD) is a progressive neurodegenerative disorder caused by an expansion of CAG repeats in the IT15 gene. The age-at-onset (AAO) of HD is inversely related to the CAG repeat length and the minimum length thought to cause HD is 36. Accurate estimation of the AAO distribution based on CAG repeat length is important for genetic counseling and the design of clinical trials. In the Cooperative Huntington's Observational Research Trial (COHORT) study, the CAG repeat length is known for the proband participants. However, whether a family member shares the huntingtin gene status (CAG expanded or not) with the proband is unknown. In this work, we use the expectation-maximization (EM) algorithm to handle the missing huntingtin gene information in first-degree family members in COHORT, assuming that a family member has the same CAG length as the proband if the family member carries a huntingtin gene mutation. We perform simulation studies to examine performance of the proposed method and apply the methods to analyze COHORT proband and family combined data. Our analyses reveal that the estimated cumulative risk of HD symptom onset obtained from the combined data is slightly lower than the risk estimated from the proband data alone.",
+ "publisher": "Progress in neuro-psychopharmacology & biological psychiatry",
+ "issn": "0278-5846",
+ "date": "2006-12-13",
+ "abstract": "Pharmacological studies indicate a dysregulation of the serotonergic system in obsessive-compulsive disorder (OCD). A variable number tandem repeats (VNTR) polymorphism with three alleles (Stin2.9, Stin2.10, Stin2.12) has been described in intron 2 of the serotonin transporter (5-HTT) gene. This polymorphism has been associated with unipolar depression, bipolar disorder, schizophrenia, and anxiety disorders including OCD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23476655"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17174018"
},
{
- "id": "pmid:22179316",
+ "id": "pmid:17115386",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/22179316",
- "title": "Sirt1 mediates neuroprotection from mutant huntingtin by activation of the TORC1 and CREB transcriptional pathway.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17115386",
+ "title": "Autopsy-proven Huntington's disease with 29 trinucleotide repeats.",
"type": "article-journal",
- "doi": "10.1038/nm.2559",
+ "doi": "10.1002/mds.21195",
"authors": [
- ["Hyunkyung", "Jeong"],
- ["Dena E", "Cohen"],
- ["Libin", "Cui"],
- ["Andrea", "Supinski"],
- ["Jeffrey N", "Savas"],
- ["Joseph R", "Mazzulli"],
- ["John R", "Yates"],
- ["Laura", "Bordone"],
- ["Leonard", "Guarente"],
- ["Dimitri", "Krainc"]
+ ["Christopher", "Kenney"],
+ ["Suzanne", "Powell"],
+ ["Joseph", "Jankovic"]
],
- "publisher": "Nature medicine",
- "issn": "1546-170X",
- "date": "2011-12-18",
- "abstract": "Sirt1, a NAD-dependent protein deacetylase, has emerged as a key regulator of mammalian transcription in response to cellular metabolic status and stress. Here we show that Sirt1 has a neuroprotective role in models of Huntington's disease, an inherited neurodegenerative disorder caused by a glutamine repeat expansion in huntingtin protein (HTT). Brain-specific knockout of Sirt1 results in exacerbation of brain pathology in a mouse model of Huntington's disease, whereas overexpression of Sirt1 improves survival, neuropathology and the expression of brain-derived neurotrophic factor (BDNF) in Huntington's disease mice. We show that Sirt1 deacetylase activity directly targets neurons to mediate neuroprotection from mutant HTT. The neuroprotective effect of Sirt1 requires the presence of CREB-regulated transcription coactivator 1 (TORC1), a brain-specific modulator of CREB activity. We show that under normal conditions, Sirt1 deacetylates and activates TORC1 by promoting its dephosphorylation and its interaction with CREB. We identified BDNF as a key target of Sirt1 and TORC1 transcriptional activity in both normal and Huntington's disease neurons. Mutant HTT interferes with the TORC1-CREB interaction to repress BDNF transcription, and Sirt1 rescues this defect in vitro and in vivo. These studies suggest a key role for Sirt1 in transcriptional networks in both the normal and Huntington's disease brain and offer an opportunity for therapeutic development.",
+ "publisher": "Movement disorders : official journal of the Movement Disorder Society",
+ "issn": "0885-3185",
+ "date": "2007-01-01",
+ "abstract": "Huntington's disease (HD) is a neurodegenerative disorder associated with expansion of CAG trinucleotide repeats in the huntingtin gene. A minimum of 36 CAG repeats is usually reported in patients with clinical features of HD; 30 to 35 repeats represent an intermediate range. Here we report a 65-year-old male with autopsy-proven HD and 29 CAG repeats.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22179316"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17115386"
},
{
- "id": "pmid:22011578",
+ "id": "pmid:17018562",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/22011578",
- "title": "Ser46 phosphorylation and prolyl-isomerase Pin1-mediated isomerization of p53 are key events in p53-dependent apoptosis induced by mutant huntingtin.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17018562",
+ "title": "Replication of twelve association studies for Huntington's disease residual age of onset in large Venezuelan kindreds.",
"type": "article-journal",
- "doi": "10.1073/pnas.1106198108",
+ "doi": "10.1136/jmg.2006.045153",
"authors": [
- ["Alice", "Grison"],
- ["Fiamma", "Mantovani"],
- ["Anna", "Comel"],
- ["Elena", "Agostoni"],
- ["Stefano", "Gustincich"],
- ["Francesca", "Persichetti"],
- ["Giannino", "Del Sal"]
+ ["J M", "Andresen"],
+ ["J", "Gay\u00e1n"],
+ ["S S", "Cherny"],
+ ["D", "Brocklebank"],
+ ["G", "Alkorta-Aranburu"],
+ ["E A", "Addis"],
+ ["L R", "Cardon"],
+ ["D E", "Housman"],
+ ["N S", "Wexler"]
],
- "publisher": "Proceedings of the National Academy of Sciences of the United States of America",
- "issn": "1091-6490",
- "date": "2011-10-19",
- "abstract": "Huntington disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in the gene coding for huntingtin protein. Several mechanisms have been proposed by which mutant huntingtin (mHtt) may trigger striatal neurodegeneration, including mitochondrial dysfunction, oxidative stress, and apoptosis. Furthermore, mHtt induces DNA damage and activates a stress response. In this context, p53 plays a crucial role in mediating mHtt toxic effects. Here we have dissected the pathway of p53 activation by mHtt in human neuronal cells and in HD mice, with the aim of highlighting critical nodes that may be pharmacologically manipulated for therapeutic intervention. We demonstrate that expression of mHtt causes increased phosphorylation of p53 on Ser46, leading to its interaction with phosphorylation-dependent prolyl isomerase Pin1 and consequent dissociation from the apoptosis inhibitor iASPP, thereby inducing the expression of apoptotic target genes. Inhibition of Ser46 phosphorylation by targeting homeodomain-interacting protein kinase 2 (HIPK2), PKC\u03b4, or ataxia telangiectasia mutated kinase, as well as inhibition of the prolyl isomerase Pin1, prevents mHtt-dependent apoptosis of neuronal cells. These results provide a rationale for the use of small-molecule inhibitors of stress-responsive protein kinases and Pin1 as a potential therapeutic strategy for HD treatment.",
+ "publisher": "Journal of medical genetics",
+ "issn": "1468-6244",
+ "date": "2006-10-03",
+ "abstract": "The major determinant of age of onset in Huntington's disease is the length of the causative triplet CAG repeat. Significant variance remains, however, in residual age of onset even after repeat length is factored out. Many genetic polymorphisms have previously shown evidence of association with age of onset of Huntington's disease in several different populations.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22011578"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17018562"
},
{
- "id": "pmid:21989477",
+ "id": "pmid:17018277",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21989477",
- "title": "NMDA receptor gene variations as modifiers in Huntington disease: a replication study.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17018277",
+ "title": "Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration.",
"type": "article-journal",
- "doi": "10.1371/currents.rrn1247",
+ "doi": "10.1016/j.cell.2006.09.015",
"authors": [
- ["Carsten", "Saft"],
- ["J\u00f6rg T", "Epplen"],
- ["Stefan", "Wieczorek"],
- ["G Bernhard", "Landwehrmeyer"],
- ["Raymund A C", "Roos"],
- ["Justo Garcia", "de Yebenes"],
- ["Matthias", "Dose"],
- ["Sarah J", "Tabrizi"],
- ["David", "Craufurd"],
- ["Larissa", "Arning"]
+ ["Libin", "Cui"],
+ ["Hyunkyung", "Jeong"],
+ ["Fran", "Borovecki"],
+ ["Christopher N", "Parkhurst"],
+ ["Naoko", "Tanese"],
+ ["Dimitri", "Krainc"]
],
- "publisher": "PLoS currents",
- "issn": "2157-3999",
- "date": "2011-10-04",
- "abstract": "Several candidate modifier genes which, in addition to the pathogenic CAG repeat expansion, influence the age at onset (AO) in Huntington disease (HD) have already been described. The aim of this study was to replicate association of variations in the N-methyl D-aspartate receptor subtype genes GRIN2A and GRIN2B in the \"REGISTRY\" cohort from the European Huntington Disease Network (EHDN). The analyses did replicate the association reported between the GRIN2A rs2650427 variation and AO in the entire cohort. Yet, when subjects were stratified by AO subtypes, we found nominally significant evidence for an association of the GRIN2A rs1969060 variation and the GRIN2B rs1806201 variation. These findings further implicate the N-methyl D-aspartate receptor subtype genes as loci containing variation associated with AO in HD.",
+ "publisher": "Cell",
+ "issn": "0092-8674",
+ "date": "2006-10-06",
+ "abstract": "Huntington's disease (HD) is an inherited neurodegenerative disease caused by a glutamine repeat expansion in huntingtin protein. Transcriptional deregulation and altered energy metabolism have been implicated in HD pathogenesis. We report here that mutant huntingtin causes disruption of mitochondrial function by inhibiting expression of PGC-1alpha, a transcriptional coactivator that regulates several metabolic processes, including mitochondrial biogenesis and respiration. Mutant huntingtin represses PGC-1alpha gene transcription by associating with the promoter and interfering with the CREB/TAF4-dependent transcriptional pathway critical for the regulation of PGC-1alpha gene expression. Crossbreeding of PGC-1alpha knockout (KO) mice with HD knockin (KI) mice leads to increased neurodegeneration of striatal neurons and motor abnormalities in the HD mice. Importantly, expression of PGC-1alpha partially reverses the toxic effects of mutant huntingtin in cultured striatal neurons. Moreover, lentiviral-mediated delivery of PGC-1alpha in the striatum provides neuroprotection in the transgenic HD mice. These studies suggest a key role for PGC-1alpha in the control of energy metabolism in the early stages of HD pathogenesis.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21989477"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17018277"
},
{
- "id": "pmid:21962718",
+ "id": "pmid:16987871",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21962718",
- "title": "Clinical and genetic characteristics in patients with Huntington's Disease from Argentina.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/16987871",
+ "title": "Cholinergic neuronal defect without cell loss in Huntington's disease.",
"type": "article-journal",
- "doi": "10.1016/j.parkreldis.2011.09.011",
+ "doi": "10.1093/hmg/ddl252",
"authors": [
- ["Emilia", "Gatto"],
- ["Virginia", "Parisi"],
- ["Gabriel", "Persi"],
- ["Daniela Paola", "Converso"],
- ["Jos\u00e9 Luis", "Etcheverry"],
- ["Viviana", "Varela"],
- ["Ariel", "Lopez"],
- ["Liliana", "Alba"],
- ["Gustavo", "Fretchel"]
+ ["Ruben", "Smith"],
+ ["Hinfan", "Chung"],
+ ["Sara", "Rundquist"],
+ ["Marion L C", "Maat-Schieman"],
+ ["Lesley", "Colgan"],
+ ["Elisabet", "Englund"],
+ ["Yong-Jian", "Liu"],
+ ["Raymund A C", "Roos"],
+ ["Richard L M", "Faull"],
+ ["Patrik", "Brundin"],
+ ["Jia-Yi", "Li"]
],
- "publisher": "Parkinsonism & related disorders",
- "issn": "1873-5126",
- "date": "2011-10-01",
- "abstract": "Huntington's Disease (HD) is a neurodegenerative disease, caused by the expansion of an unstable (CAG)(n) in the HTT gene. There is scarce data about the disease in Argentina.",
+ "publisher": "Human molecular genetics",
+ "issn": "0964-6906",
+ "date": "2006-09-20",
+ "abstract": "Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG-repeat expansion in the huntingtin (IT15) gene. The striatum is one of the regions most affected by neurodegeneration, resulting in the loss of the medium-sized spiny neurons. Traditionally, the large cholinergic striatal interneurons are believed to be spared. Recent studies demonstrate that neuronal dysfunction without cell death also plays an important role in early and mid-stages of the disease. Here, we report that cholinergic transmission is affected in a HD transgenic mouse model (R6/1) and in tissues from HD patients. Stereological analysis shows no loss of cholinergic neurons in the striatum or septum in R6/1 mice. In contrast, the levels of mRNA and protein for vesicular acetylcholine transporter (VAChT) and choline acetyltransferase (ChAT) are decreased in the striatum and cortex, and acetylcholine esterase activity is lowered in the striatum of R6/1 mice already at young ages. Accordingly, VAChT is also reduced in striatal tissue from patients with HD. The decrease of VAChT in the patient samples studied is restricted to the striatum and does not occur in the hippocampus or the spinal cord. The expression and localization of REST/NRSF, a transcriptional regulator for the VAChT and ChAT genes, are not altered in cholinergic neurons. We show that the R6/1 mice exhibit severe deficits in learning and reference memory. Taken together, our data show that the cholinergic system is dysfunctional in R6/1 and HD patients. Consequently, they provide a rationale for testing of pro-cholinergic drugs in this disease.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21962718"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16987871"
},
{
- "id": "pmid:21907324",
+ "id": "pmid:16925544",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21907324",
- "title": "Striatal volume contributes to the prediction of onset of Huntington disease in incident cases.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/16925544",
+ "title": "Juvenile Huntington disease.",
"type": "article-journal",
- "doi": "10.1016/j.biopsych.2011.07.030",
+ "doi": "10.1111/j.1440-1754.2006.00921.x",
"authors": [
- ["Elizabeth H", "Aylward"],
- ["Dawei", "Liu"],
- ["Peggy C", "Nopoulos"],
- ["Christopher A", "Ross"],
- ["Ronald K", "Pierson"],
- ["James A", "Mills"],
- ["Jeffrey D", "Long"],
- ["Jane S", "Paulsen"]
+ ["Nimeshan", "Geevasinga"],
+ ["Fiona H", "Richards"],
+ ["Kristi J", "Jones"],
+ ["Monique M", "Ryan"]
],
- "publisher": "Biological psychiatry",
- "issn": "1873-2402",
- "date": "2011-09-09",
- "abstract": "Previous neuroimaging research indicates that brain atrophy in Huntington disease (HD) begins many years before movement abnormalities become severe enough to warrant diagnosis. Most clinical trials being planned for individuals in the prediagnostic stage of HD propose to use delay of disease onset as the primary outcome measure. Although formulas have been developed based on age and CAG repeat length, to predict when HD motor onset will occur, it would be useful to have additional measures that can improve the accuracy of prediction of disease onset.",
+ "publisher": "Journal of paediatrics and child health",
+ "issn": "1034-4810",
+ "date": "2006-09-01",
+ "abstract": "Huntington disease (HD) is a dominantly inherited neurodegenerative disorder related to expansion of a triplet repeat sequence in the huntington gene on chromosome 4. Adult HD usually presents with chorea and personality changes. Juvenile HD is far less common and presents with parkinsonism, dystonia and seizures. We report a case of juvenile HD, showing extreme anticipation, in which diagnosis was delayed because of failure to recognise the significance of the family history and the characteristic clinical and radiologic features of this condition.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21907324"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16925544"
},
{
- "id": "pmid:21897851",
+ "id": "pmid:16918952",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21897851",
- "title": "Quantification of age-dependent somatic CAG repeat instability in Hdh CAG knock-in mice reveals different expansion dynamics in striatum and liver.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/16918952",
+ "title": "The androgen receptor gene CAG repeat polymorphism does not predict increased risk of heart disease: longitudinal results from the Massachusetts Male Ageing Study.",
"type": "article-journal",
- "doi": "10.1371/journal.pone.0023647",
+ "doi": "10.1111/j.1365-2265.2006.02598.x",
"authors": [
- ["Jong-Min", "Lee"],
- ["Ricardo Mouro", "Pinto"],
- ["Tammy", "Gillis"],
- ["Jason C", "St Claire"],
- ["Vanessa C", "Wheeler"]
+ ["Stephanie T", "Page"],
+ ["Varant", "Kupelian"],
+ ["William J", "Bremner"],
+ ["John B", "McKinlay"]
],
- "publisher": "PloS one",
- "issn": "1932-6203",
- "date": "2011-08-29",
- "abstract": "Age at onset of Huntington's disease (HD) is largely determined by the CAG trinucleotide repeat length in the HTT gene. Importantly, the CAG repeat undergoes tissue-specific somatic instability, prevalent in brain regions that are disease targets, suggesting a potential role for somatic CAG repeat instability in modifying HD pathogenesis. Thus, understanding underlying mechanisms of somatic CAG repeat instability may lead to discoveries of novel therapeutics for HD. Investigation of the dynamics of the CAG repeat size changes over time may provide insights into the mechanisms underlying CAG repeat instability.",
+ "publisher": "Clinical endocrinology",
+ "issn": "0300-0664",
+ "date": "2006-09-01",
+ "abstract": "Sex steroids may contribute to the increased prevalence of heart disease (HD) in men compared to age-matched women. Androgens bind their cognate receptor, and androgen action is inversely proportional to the number of CAG repeats in exon 1 of the androgen receptor gene. Longer, less androgenic CAG repeats have been associated with higher high-density lipoprotein (HDL) levels, which might protect against HD. Therefore, we hypothesized that CAG repeat length contributes to HD risk in men.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21897851"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16918952"
},
{
- "id": "pmid:21896309",
+ "id": "pmid:16914060",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21896309",
- "title": "Protective role of the ubiquitin binding protein Tollip against the toxicity of polyglutamine-expansion proteins.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/16914060",
+ "title": "Genome-wide significance for a modifier of age at neurological onset in Huntington's disease at 6q23-24: the HD MAPS study.",
"type": "article-journal",
- "doi": "10.1016/j.neulet.2011.08.043",
+ "doi": "10.1186/1471-2350-7-71",
"authors": [
- ["Asami", "Oguro"],
- ["Hiroshi", "Kubota"],
- ["Miho", "Shimizu"],
- ["Shoichi", "Ishiura"],
- ["Yoriko", "Atomi"]
+ ["Jian-Liang", "Li"],
+ ["Michael R", "Hayden"],
+ ["Simon C", "Warby"],
+ ["Alexandra", "Durr"],
+ ["Patrick J", "Morrison"],
+ ["Martha", "Nance"],
+ ["Christopher A", "Ross"],
+ ["Russell L", "Margolis"],
+ ["Adam", "Rosenblatt"],
+ ["Ferdinando", "Squitieri"],
+ ["Luigi", "Frati"],
+ ["Estrella", "G\u00f3mez-Tortosa"],
+ ["Carmen Ayuso", "Garc\u00eda"],
+ ["Oksana", "Suchowersky"],
+ ["Mary Lou", "Klimek"],
+ ["Ronald J A", "Trent"],
+ ["Elizabeth", "McCusker"],
+ ["Andrea", "Novelletto"],
+ ["Marina", "Frontali"],
+ ["Jane S", "Paulsen"],
+ ["Randi", "Jones"],
+ ["Tetsuo", "Ashizawa"],
+ ["Alice", "Lazzarini"],
+ ["Vanessa C", "Wheeler"],
+ ["Ranjana", "Prakash"],
+ ["Gang", "Xu"],
+ ["Luc", "Djouss\u00e9"],
+ ["Jayalakshmi Srinidhi", "Mysore"],
+ ["Tammy", "Gillis"],
+ ["Michael", "Hakky"],
+ ["L Adrienne", "Cupples"],
+ ["Marie H", "Saint-Hilaire"],
+ ["Jang-Ho J", "Cha"],
+ ["Steven M", "Hersch"],
+ ["John B", "Penney"],
+ ["Madaline B", "Harrison"],
+ ["Susan L", "Perlman"],
+ ["Andrea", "Zanko"],
+ ["Ruth K", "Abramson"],
+ ["Anthony J", "Lechich"],
+ ["Ayana", "Duckett"],
+ ["Karen", "Marder"],
+ ["P Michael", "Conneally"],
+ ["James F", "Gusella"],
+ ["Marcy E", "MacDonald"],
+ ["Richard H", "Myers"]
],
- "publisher": "Neuroscience letters",
- "issn": "1872-7972",
- "date": "2011-08-27",
- "abstract": "Huntington disease (HD) is caused by the expansion of polyglutamine (polyQ) repeats in the amino-terminal of hungtintin (htt). PolyQ-expanded htt forms intracellular ubiquitinated aggregates in neurons and causes neuronal cell death. Here, utilizing a HD cellular model, we report that Tollip, an ubiquitin binding protein that participates in intracellular transport via endosomes, co-localizes with and stimulates aggregation of polyQ-expanded amino-terminal htt. Furthermore, we demonstrate that Tollip protects cells against the toxicity of polyQ-expanded htt. We propose that association of Tollip with polyubiquitin accelerates aggregation of toxic htt species into inclusions and thus provides a cell protective role by sequestration.",
+ "publisher": "BMC medical genetics",
+ "issn": "1471-2350",
+ "date": "2006-08-17",
+ "abstract": "Age at onset of Huntington's disease (HD) is correlated with the size of the abnormal CAG repeat expansion in the HD gene; however, several studies have indicated that other genetic factors also contribute to the variability in HD age at onset. To identify modifier genes, we recently reported a whole-genome scan in a sample of 629 affected sibling pairs from 295 pedigrees, in which six genomic regions provided suggestive evidence for quantitative trait loci (QTL), modifying age at onset in HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21896309"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16914060"
},
{
- "id": "pmid:21555070",
+ "id": "pmid:16690085",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21555070",
- "title": "An antisense CAG repeat transcript at JPH3 locus mediates expanded polyglutamine protein toxicity in Huntington's disease-like 2 mice.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/16690085",
+ "title": "Association between serotonin transporter gene and borderline personality disorder.",
"type": "article-journal",
- "doi": "10.1016/j.neuron.2011.03.021",
+ "doi": "10.1016/j.jpsychires.2006.03.010",
"authors": [
- ["Brian", "Wilburn"],
- ["Dobrila D", "Rudnicki"],
- ["Jing", "Zhao"],
- ["Tara Murphy", "Weitz"],
- ["Yin", "Cheng"],
- ["Xiaofeng", "Gu"],
- ["Erin", "Greiner"],
- ["Chang Sin", "Park"],
- ["Nan", "Wang"],
- ["Bryce L", "Sopher"],
- ["Albert R", "La Spada"],
- ["Alex", "Osmand"],
- ["Russell L", "Margolis"],
- ["Yi E", "Sun"],
- ["X William", "Yang"]
+ ["Xingqun", "Ni"],
+ ["Kirsten", "Chan"],
+ ["Natalie", "Bulgin"],
+ ["Tricia", "Sicard"],
+ ["Ramprasad", "Bismil"],
+ ["Shelley", "McMain"],
+ ["James L", "Kennedy"]
],
- "publisher": "Neuron",
- "issn": "1097-4199",
- "date": "2011-05-12",
- "abstract": "Huntington's disease-like-2 (HDL2) is a phenocopy of Huntington's disease caused by CTG/CAG repeat expansion at the Junctophilin-3 (JPH3) locus. The mechanisms underlying HDL2 pathogenesis remain unclear. Here we developed a BAC transgenic mouse model of HDL2 (BAC-HDL2) that exhibits progressive motor deficits, selective neurodegenerative pathology, and ubiquitin-positive nuclear inclusions (NIs). Molecular analyses reveal a promoter at the transgene locus driving the expression of a CAG repeat transcript (HDL2-CAG) from the strand antisense to JPH3, which encodes an expanded polyglutamine (polyQ) protein. Importantly, BAC-HDL2 mice, but not control BAC mice, accumulate polyQ-containing NIs in a pattern strikingly similar to those in the patients. Furthermore, BAC mice with genetic silencing of the expanded CUG transcript still express HDL2-CAG transcript and manifest polyQ pathogenesis. Finally, studies of HDL2 mice and patients revealed CBP sequestration into NIs and evidence for interference of CBP-mediated transcriptional activation. These results suggest overlapping polyQ-mediated pathogenic mechanisms in HD and HDL2.",
+ "publisher": "Journal of psychiatric research",
+ "issn": "0022-3956",
+ "date": "2006-05-11",
+ "abstract": "Borderline personality disorder (BPD) is characterized by a pervasive pattern of instability in regulation of emotion, interpersonal relationships, self-image, and impulse control beginning in early adulthood. BPD affects about 1-2% of the general population and has a high mortality rate as a result of suicide and impulsive behaviour. The serotonin transporter gene (5-HTT) is considered as a candidate gene for BPD as multiple lines of evidence have suggested that it plays an important role in suicide, impulsive behaviour, and emotional liability. To test for an association between 5-HTT and BPD, we genotyped three common polymorphisms: the serotonin transporter linked promoter region (5-HTTLPR); a variable number of tandem repeat (VNTR) in intron 2, and a single nucleotide variant (A/G) within the LPR region. Eighty-nine Caucasian patients with BPD and 269 Caucasian healthy controls were analyzed. The program UNPHASED was used to compare allele and haplotype frequencies between cases and controls. Significant differences in allele frequencies of the VNTR marker (p=0.012) and haplotype frequencies (p=0.002) between patients and controls were found. Compared with healthy controls, patients with BPD showed higher frequencies of the 10 repeat of the VNTR marker and the S-10 haplotype, and lower 12 repeat and L(A)-12 haplotype. Our results suggest that the serotonin transporter gene may play a role in the aetiology of borderline personality disorder.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21555070"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16690085"
},
{
- "id": "pmid:21540131",
+ "id": "pmid:16687439",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21540131",
- "title": "Parent-of-origin differences of mutant HTT CAG repeat instability in Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/16687439",
+ "title": "Genetic background modifies nuclear mutant huntingtin accumulation and HD CAG repeat instability in Huntington's disease knock-in mice.",
"type": "article-journal",
- "doi": "10.1016/j.ejmg.2011.04.002",
+ "doi": "10.1093/hmg/ddl125",
"authors": [
- ["N Ahmad", "Aziz"],
- ["Martine J", "van Belzen"],
- ["Ilona D", "Coops"],
- ["Ren\u00e9 D M", "Belfroid"],
- ["Raymund A C", "Roos"]
+ ["Alejandro", "Lloret"],
+ ["Ella", "Dragileva"],
+ ["Allison", "Teed"],
+ ["Janice", "Espinola"],
+ ["Elisa", "Fossale"],
+ ["Tammy", "Gillis"],
+ ["Edith", "Lopez"],
+ ["Richard H", "Myers"],
+ ["Marcy E", "MacDonald"],
+ ["Vanessa C", "Wheeler"]
],
- "publisher": "European journal of medical genetics",
- "issn": "1878-0849",
- "date": "2011-04-23",
- "abstract": "Huntington's disease (HD) is a progressive autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion in the HD gene (HTT). The CAG domain of mutant HTT is unstable upon intergenerational transmission, however, little is known about the underlying mechanisms.",
+ "publisher": "Human molecular genetics",
+ "issn": "0964-6906",
+ "date": "2006-05-10",
+ "abstract": "Genetically precise models of Huntington's disease (HD), Hdh CAG knock-in mice, are powerful systems in which phenotypes associated with expanded HD CAG repeats are studied. To dissect the genetic pathways that underlie such phenotypes, we have generated Hdh(Q111) knock-in mouse lines that are congenic for C57BL/6, FVB/N and 129Sv inbred genetic backgrounds and investigated four Hdh(Q111) phenotypes in these three genetic backgrounds: the intergenerational instability of the HD CAG repeat and the striatal-specific somatic HD CAG repeat expansion, nuclear mutant huntingtin accumulation and intranuclear inclusion formation. Our results reveal increased intergenerational and somatic instability of the HD CAG repeat in C57BL/6 and FVB/N backgrounds compared with the 129Sv background. The accumulation of nuclear mutant huntingtin and the formation of intranuclear inclusions were fastest in the C57BL/6 background, slowest in the 129Sv background and intermediate in the FVB/N background. Inbred strain-specific differences were independent of constitutive HD CAG repeat size and did not correlate with Hdh mRNA levels. These data provide evidence for genetic modifiers of both intergenerational HD CAG repeat instability and striatal-specific phenotypes. Different relative contributions of C57BL/6 and 129Sv genetic backgrounds to the onset of nuclear mutant huntingtin and somatic HD CAG repeat expansion predict that the initiation of each of these two phenotypes is modified by different genes. Our findings set the stage for defining disease-related genetic pathways that will ultimately provide insight into disease mechanism.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21540131"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16687439"
},
{
- "id": "pmid:21519949",
+ "id": "pmid:16626669",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21519949",
- "title": "Genotype-, aging-dependent abnormal caspase activity in Huntington disease blood cells.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/16626669",
+ "title": "DNA microarray analysis of striatal gene expression in symptomatic transgenic Huntington's mice (R6/2) reveals neuroinflammation and insulin associations.",
"type": "article-journal",
- "doi": "10.1007/s00702-011-0646-1",
+ "doi": "10.1016/j.brainres.2006.02.102",
"authors": [
- ["Ferdinando", "Squitieri"],
- ["Vittorio", "Maglione"],
- ["Sara", "Orobello"],
- ["Francesco", "Fornai"]
+ ["Susan F", "Crocker"],
+ ["Willard J", "Costain"],
+ ["Harold A", "Robertson"]
],
- "publisher": "Journal of neural transmission (Vienna, Austria : 1996)",
- "issn": "1435-1463",
- "date": "2011-04-26",
- "abstract": "Huntington's Disease (HD) is caused by trinucleotide CAG repeat expansion >36 in huntingtin (htt), a protein with several documented functions. The elongated polyglutamine (polyQ) stretch in the N-terminal region of htt leads to dysfunctional and degenerative events in neurons and peripheral tissues. In this study, by extending the analysis to several caspase activities (i.e. caspase 2, 3, 6, 8 and 9), we describe genotype- and time- dependent caspase activity abnormalities, decreased cell viability and a large set of alterations in mitochondria morphology, in cultured blood cells from HD patients. Patients homozygous for CAG repeat mutations and heterozygous with high size mutations causing juvenile onset (JHD) presented significantly increased caspase 2, 3, 6, 8 and 9 activities, decreased cell viability and pronounced morphological abnormalities, compared with cells carrying low mutation size and controls. After cyanide treatment, all caspases increased their activities in homozygous and highly expanded heterozygous cells, caspase 8 and 9 increased also in those cells carrying low-size mutations, remarking their key role as 'caspase initiators' in HD. The remarkable ageing-dependent abnormalities in peripheral cells carrying particularly toxic mutations (i.e. homozygotes' and JHD's blood cells) points out the potential dependence of clinical HD development and progression on either mutated htt dosage or missing wild type htt. Peripheral tissues (i.e. blood cells) may theoretically represent an important tool for studying HD mechanisms and searching for new biomarkers, according to the patients' genotype.",
+ "publisher": "Brain research",
+ "issn": "0006-8993",
+ "date": "2006-04-19",
+ "abstract": "Huntington's disease (HD) is an inherited, progressive neurodegenerative disorder caused by CAG repeat expansion in the gene that codes for the protein huntingtin. The underlying neuropathological events leading to the selectivity of striatal neuronal loss are unknown. However, the huntingtin mutation interferes at several levels of normal cell function. The complexity of this disease makes microarray analysis an appealing technique to begin the identification of common pathways that may contribute to the pathology. In this study, striatal tissue was extracted for gene expression profiling from wild-type and symptomatic transgenic Huntington mice (R6/2) expressing part of the human Huntington's disease gene. We interrogated a 15 K high-density mouse EST array not previously used for HD and identified 170 significantly differentially expressed ESTs in symptomatic R6/2 mice. Of the 80 genes with known function, 9 genes had previously been identified as altered in HD. 71 known genes were associated with HD for the first time. The data obtained from this study confirm and extend previous observations using DNA microarray techniques on genetic models for HD, revealing novel changes in expression in a number of genes not previously associated with HD. Further bioinformatic analysis, using software to construct biological association maps, focused attention on proteins such as insulin and TH1-mediated cytokines, suggesting that they may be important regulators of affected genes. These results may provide insight into the regulation and interaction of genes that contribute to adaptive and pathological processes involved in HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21519949"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16626669"
},
{
- "id": "pmid:21427085",
+ "id": "pmid:16564426",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21427085",
- "title": "Inhibition of mutant huntingtin expression by RNA duplex targeting expanded CAG repeats.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/16564426",
+ "title": "Normal sensitivity to excitotoxicity in a transgenic Huntington's disease rat.",
"type": "article-journal",
- "doi": "10.1093/nar/gkr156",
+ "doi": "10.1016/j.brainresbull.2006.01.003",
"authors": [
- ["Agnieszka", "Fiszer"],
- ["Agnieszka", "Mykowska"],
- ["Wlodzimierz J", "Krzyzosiak"]
+ ["C", "Winkler"],
+ ["J M A C", "Gil"],
+ ["I M", "Ara\u00fajo"],
+ ["O", "Riess"],
+ ["T", "Skripuletz"],
+ ["S", "von H\u00f6rsten"],
+ ["A", "Peters\u00e9n"]
],
- "publisher": "Nucleic acids research",
- "issn": "1362-4962",
- "date": "2011-03-22",
- "abstract": "The specific silencing of the gene of interest is the major objective of RNA interference technology; therefore, unique sequences but not abundant sequence repeats are targeted by silencing reagents. Here, we describe the targeting of expanded CAG repeats that occur in transcripts derived from the mutant allele of the gene implicated in Huntington's disease (HD) in the presence of the normal allele and other human mRNAs containing CAG and CUG repeat tracts. We show that a high degree of silencing selectivity may be achieved between the repeated sequences. We demonstrate preferential suppression of the mutant huntingtin allele and concomitant activation of the normal huntingtin allele in cell lines derived from HD patients that were transfected with short RNA duplexes composed of CAG and CUG repeats containing mutations at specific positions. These effects may lead to promising therapeutic modalities for HD, a condition for which no therapy presently exists.",
+ "publisher": "Brain research bulletin",
+ "issn": "0361-9230",
+ "date": "2006-01-20",
+ "abstract": "Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by a CAG repeat expansion in the HD gene. Excitotoxic cell damage by excessive stimulation of glutamate receptors has been hypothesized to contribute to the pathogenesis of HD. Transgenic mouse models of HD have shown variable sensitivity to excitotoxicity. The models differ in the genetic background, the type and length of the promoter driving the transgene expression, the CAG repeat length and/or the HD gene construct length. Furthermore, one has to differentiate whether transgenic or knock-in models have been used. All these factors may be involved in determining the responsiveness to an excitotoxic insult. Here, we explored the responsiveness to excitotoxic damage using a transgenic HD rat model carrying 22% of the rat HD gene which is driven by the rat HD promoter and which harbors 51 CAG repeats. 3 and 18 months old transgenic HD rats and their wild-type littermates received unilateral intrastriatal injections of the glutamate analogue quinolinic acid. Lesion size was assessed 7 days later using the degenerative stain Fluoro-Jade and by immunohistochemistry for the neuronal protein NeuN. No difference in susceptibility to excitotoxicity was found between the groups. Our study supports mouse data showing maintained susceptibility to excitotoxicity with the expression of around 25% of the full HD gene. Differences in sensitivity to excitotoxicity between genetic animal models of HD may be dependent on the length of the expressed HD gene although additional factors are also likely to be important.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21427085"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16564426"
},
{
- "id": "pmid:21370269",
+ "id": "pmid:16526033",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21370269",
- "title": "An item response analysis of the motor and behavioral subscales of the unified Huntington's disease rating scale in huntington disease gene expansion carriers.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/16526033",
+ "title": "Intergeneration CAG expansion and contraction in a Chinese HD family.",
"type": "article-journal",
- "doi": "10.1002/mds.23574",
+ "doi": "10.1002/ajmg.b.30261",
"authors": [
- ["Anthony L", "Vaccarino"],
- ["Karen", "Anderson"],
- ["Beth", "Borowsky"],
- ["Kevin", "Duff"],
- ["Joseph", "Giuliano"],
- ["Mark", "Guttman"],
- ["Aileen K", "Ho"],
- ["Michael", "Orth"],
- ["Jane S", "Paulsen"],
- ["Terrence", "Sills"],
- ["Daniel P", "van Kammen"],
- ["Kenneth R", "Evans"]
+ ["Yanping", "Tang"],
+ ["Ying", "Wang"],
+ ["Ping", "Yang"],
+ ["Yuan", "Liu"],
+ ["Bo", "Wang"],
+ ["Robert", "Podolsky"],
+ ["Richard", "McIndoe"],
+ ["Cong-Yi", "Wang"]
],
- "publisher": "Movement disorders : official journal of the Movement Disorder Society",
- "issn": "1531-8257",
- "date": "2011-03-02",
- "abstract": "Although the Unified Huntington's Disease Rating Scale (UHDRS) is widely used in the assessment of Huntington disease (HD), the ability of individual items to discriminate individual differences in motor or behavioral manifestations has not been extensively studied in HD gene expansion carriers without a motor-defined clinical diagnosis (ie, prodromal-HD or prHD). To elucidate the relationship between scores on individual motor and behavioral UHDRS items and total score for each subscale, a nonparametric item response analysis was performed on retrospective data from 2 multicenter longitudinal studies. Motor and behavioral assessments were supplied for 737 prHD individuals with data from 2114 visits (PREDICT-HD) and 686 HD individuals with data from 1482 visits (REGISTRY). Option characteristic curves were generated for UHDRS subscale items in relation to their subscale score. In prHD, overall severity of motor signs was low, and participants had scores of 2 or above on very few items. In HD, motor items that assessed ocular pursuit, saccade initiation, finger tapping, tandem walking, and to a lesser extent, saccade velocity, dysarthria, tongue protrusion, pronation/supination, Luria, bradykinesia, choreas, gait, and balance on the retropulsion test were found to discriminate individual differences across a broad range of motor severity. In prHD, depressed mood, anxiety, and irritable behavior demonstrated good discriminative properties. In HD, depressed mood demonstrated a good relationship with the overall behavioral score. These data suggest that at least some UHDRS items appear to have utility across a broad range of severity, although many items demonstrate problematic features.",
+ "publisher": "American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics",
+ "issn": "1552-4841",
+ "date": "2006-04-05",
+ "abstract": "The prevalence of juvenile-onset Huntington's disease (HD) is about ten times lower than adult HD. Here we report a Chinese HD family showing both intergeneration CAG expansion and contraction. The expansion resulted from a paternal transmission which leads to juvenile-onset HD for a 17-year-old Chinese boy (III-5). More interestingly, a contraction was noticed in a maternal transmission (III-3), which changed the CAG repeat from an expanded, disease-causing allele (48 repeats) to a normal or intermediate allele (34 repeats). Of note, the contraction resulted in a deletion of 14 CAG repeats, which is much larger than previously reported contractions. Our results are consistent with previous observations in Western Caucasians that juvenile-onset HD is more likely inherited through the male germline.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21370269"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16526033"
},
{
- "id": "pmid:21347256",
+ "id": "pmid:16515395",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21347256",
- "title": "Unusual structures are present in DNA fragments containing super-long Huntingtin CAG repeats.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/16515395",
+ "title": "Serotonin transporter polymorphisms and side effects in antidepressant therapy--a pilot study.",
"type": "article-journal",
- "doi": "10.1371/journal.pone.0017119",
+ "doi": "10.2217/14622416.7.2.159",
"authors": [
- ["Daniel", "Duzdevich"],
- ["Jinliang", "Li"],
- ["Jhoon", "Whang"],
- ["Hirohide", "Takahashi"],
- ["Kunio", "Takeyasu"],
- ["David T F", "Dryden"],
- ["A Jennifer", "Morton"],
- ["J Michael", "Edwardson"]
+ ["Johannes", "Popp"],
+ ["Stefan", "Leucht"],
+ ["Stephan", "Heres"],
+ ["Werner", "Steimer"]
],
- "publisher": "PloS one",
- "issn": "1932-6203",
- "date": "2011-02-11",
- "abstract": "In the R6/2 mouse model of Huntington's disease (HD), expansion of the CAG trinucleotide repeat length beyond about 300 repeats induces a novel phenotype associated with a reduction in transcription of the transgene.",
+ "publisher": "Pharmacogenomics",
+ "issn": "1462-2416",
+ "date": "2006-03-01",
+ "abstract": "To assess the influence of the serotonin transporter variable number of tandem repeat (HTT-VNTR) polymorphism and the serotonin transporter-gene-linked polymorphic region (HTTLPR) polymorphism on development of side effects under antidepressant therapy.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21347256"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16515395"
},
{
- "id": "pmid:21211002",
+ "id": "pmid:16321399",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21211002",
- "title": "Localization of sequence variations in PGC-1\u03b1 influence their modifying effect in Huntington disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/16321399",
+ "title": "Oligoproline effects on polyglutamine conformation and aggregation.",
"type": "article-journal",
- "doi": "10.1186/1750-1326-6-1",
+ "doi": "10.1016/j.jmb.2005.10.053",
"authors": [
- ["Hong Van B", "Che"],
- ["Silke", "Metzger"],
- ["Esteban", "Portal"],
- ["Carolin", "Deyle"],
- ["Olaf", "Riess"],
- ["Huu Phuc", "Nguyen"]
+ ["Anusri", "Bhattacharyya"],
+ ["Ashwani K", "Thakur"],
+ ["Veronique M", "Chellgren"],
+ ["Geetha", "Thiagarajan"],
+ ["Angela D", "Williams"],
+ ["Brian W", "Chellgren"],
+ ["Trevor P", "Creamer"],
+ ["Ronald", "Wetzel"]
],
- "publisher": "Molecular neurodegeneration",
- "issn": "1750-1326",
- "date": "2011-01-06",
- "abstract": "Huntington disease (HD) is caused by a polyglutamine expansion of more than 35 units in the huntingtin protein. This expanded repeat length inversely correlates with the age-at-onset (AAO), however, additional genetic factors apart from the expanded CAG repeat size are thought to influence the course and the AAO in HD. Until now, among others, the gene encoding PCG-1\u03b1 (PPARGC1A) was shown to modify the AAO in two independent, however small, populations. PGC-1\u03b1 is involved in the induction of various mechanisms regulating mitochondrial biogenesis and oxidative stress defence. Furthermore, several studies have linked impairment of its function and/or its expression to HD pathogenesis. As the identification of distinct modifiers in association studies is largely dependent on the size of the observed population, we investigated nine different single nucleotide polymorphisms (SNPs) in PPARGC1A in order to replicate the disease modifying effect in more than 800 European HD patients and to identify an association with AAO in HD.",
+ "publisher": "Journal of molecular biology",
+ "issn": "0022-2836",
+ "date": "2005-11-09",
+ "abstract": "There are nine known expanded CAG repeat neurological diseases, including Huntington's disease (HD), each involving the repeat expansion of polyglutamine (polyGln) in a different protein. Similar conditions can be induced in animal models by expression of the polyGln sequence alone or in other protein contexts. Besides the polyGln sequence, the cellular context of the disease protein, and the sequence context of the polyGln within the disease protein, are both likely to contribute to polyGln physical behavior and to pathology. In HD, the N-terminal, exon-1 segment of the protein huntingtin contains the polyGln sequence immediately followed by an oligoproline region. We show here that introduction of a P10 sequence C-terminal to polyGln in synthetic peptides decreases both the rate of formation and the apparent stability of the amyloid-like aggregates associated with this family of diseases. The sequence can be trimmed to P6 without altering the suppression, but a P3 sequence is ineffective. Spacers up to at least three amino acid residues in length can be inserted between polyGln and P10 without altering this effect. There is no suppression, however, when the P10 sequence is either placed on the N-terminal side of polyGln or attached to polyGln via a side-chain tether. The nucleation mechanism of a Q40 sequence is unchanged upon addition of a P10 C-terminal extension, yielding a critical nucleus of one. The effects of oligoPro length and structural context on polyGln aggregation are correlated strongly with alterations in the circular dichroism spectra of the monomeric peptides. For example, the P10 sequence eliminates the small amount of alpha helical content otherwise exhibited by the Q40 sequence. The P10 sequence may suppress aggregation by stabilizing an aggregation-incompetent conformation of the monomer. The effect is transportable: a P10 sequence fixed to the C terminus of the sequence Abeta similarly modulates amyloid fibril formation.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21211002"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16321399"
},
{
- "id": "pmid:21192926",
+ "id": "pmid:16261565",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21192926",
- "title": "Longitudinal behavioral, cross-sectional transcriptional and histopathological characterization of a knock-in mouse model of Huntington's disease with 140 CAG repeats.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/16261565",
+ "title": "Preclinical Huntington's disease: compensatory brain responses during learning.",
"type": "article-journal",
- "doi": "10.1016/j.expneurol.2010.12.017",
+ "doi": "10.1002/ana.20684",
"authors": [
- ["Aaron C", "Rising"],
- ["Jia", "Xu"],
- ["Aaron", "Carlson"],
- ["Vincent V", "Napoli"],
- ["Eileen M", "Denovan-Wright"],
- ["Ronald J", "Mandel"]
+ ["Andrew", "Feigin"],
+ ["Maria-Felice", "Ghilardi"],
+ ["Chaorui", "Huang"],
+ ["Yilong", "Ma"],
+ ["Maren", "Carbon"],
+ ["Mark", "Guttman"],
+ ["Jane S", "Paulsen"],
+ ["Claude P", "Ghez"],
+ ["David", "Eidelberg"]
],
- "publisher": "Experimental neurology",
- "issn": "1090-2430",
- "date": "2010-12-28",
- "abstract": "The discovery of the gene mutation responsible for Huntington's disease (HD), huntingtin, in 1993 allowed for a better understanding of the pathology of and enabled the development of animal models. HD is caused by the expansion of a polyglutamine repeat region in the N-terminal of the huntingtin protein. Here we examine the behavioral, transcriptional, histopathological and anatomical characteristics of a knock-in HD mouse model with a 140 polyglutamine expansion in the huntingtin protein. This CAG 140 model contains a portion of the human exon 1 with 140 CAG repeats knocked into the mouse huntingtin gene. We have longitudinally examined the rearing behavior, accelerating rotarod, constant speed rotarod and gait for age-matched heterozygote, homozygote and non-transgenic mice and have found a significant difference in the afflicted mice. However, while there were significant differences between the non-transgenic and the knock-in mice, these behaviors were not progressive. As in HD, we show that the CAG 140 mice also have a significant decrease in striatally enriched mRNA transcripts. In addition, striatal neuronal intranuclear inclusion density increases with age. Lastly these CAG 140 mice show slight cortical thinning compared to non-transgenic mice, similarly to the cortical thinning recently reported in HD.",
+ "publisher": "Annals of neurology",
+ "issn": "0364-5134",
+ "date": "2006-01-01",
+ "abstract": "Motor sequence learning is abnormal in presymptomatic Huntington's disease (p-HD). The neural substrates underlying this early manifestation of HD are poorly understood. To study the mechanism of this cognitive abnormality in p-HD, we used positron emission tomography to record brain activity during motor sequence learning in these subjects. Eleven p-HD subjects (age, 45.8 +/- 11.0 years; CAG repeat length, 41.6 +/- 1.8) and 11 age-matched control subjects (age, 45.3 +/- 13.4 years) underwent H(2) (15)O positron emission tomography while performing a set of kinematically controlled motor sequence learning and execution tasks. Differences in regional brain activation responses between groups and conditions were assessed. In addition, we identified discrete regions in which learning-related activity correlated with performance. We found that sequence learning was impaired in p-HD subjects despite normal motor performance. In p-HD, activation responses during learning were abnormally increased in the left mediodorsal thalamus and orbitofrontal cortex (OFC; BA 11/47). Impaired learning performance in these subjects was associated with increased activation responses in the precuneus (BA 18/31). These data suggest that enhanced activation of thalamocortical pathways during motor learning can compensate for caudate degeneration in p-HD. Nonetheless, this mechanism may not be sufficient to sustain a normal level of task performance, even during the presymptomatic stage of the disease.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21192926"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16261565"
},
{
- "id": "pmid:22832606",
+ "id": "pmid:16221531",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/22832606",
- "title": "Simultaneous genotyping of multiple polymorphisms in human serotonin transporter gene and detection of novel allelic variants.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/16221531",
+ "title": "The platelet maximum number of A2A-receptor binding sites (Bmax) linearly correlates with age at onset and CAG repeat expansion in Huntington's disease patients with predominant chorea.",
"type": "article-journal",
- "doi": "10.1038/tp.2011.34",
+ "doi": "10.1016/j.neulet.2005.09.037",
"authors": [
- ["R", "Avula"],
- ["A", "Rand"],
- ["J L", "Black"],
- ["D J", "O'Kane"]
+ ["Vittorio", "Maglione"],
+ ["Milena", "Cannella"],
+ ["Tiziana", "Martino"],
+ ["Antonio", "De Blasi"],
+ ["Luigi", "Frati"],
+ ["Ferdinando", "Squitieri"]
],
- "publisher": "Translational psychiatry",
- "issn": "2158-3188",
- "date": "2011-08-16",
- "abstract": "The serotonin transporter, called SLC6A4, SERT or 5-HTT, modulates neurotransmission by removal of serotonin from the synapse of serotonergic neurons, facilitating serotonin reuptake into the presynaptic terminus. Selective serotonin reuptake inhibitors block the action of the serotonin transporter and are used to treat depression and other neuropsychiatric disorders. Three polymorphisms in the 5-HTT gene have been implicated in treatment response and neuropsychiatric disorders. A 44-bp promoter ins/del polymorphism (5-HTTLPR) produces primarily long and/or short alleles due to either 14 (short) or 16 (long) repeats of variably conserved 20-23 bp units. Also implicated, a 17-18 bp variable number tandem repeat found in intron2 (StIn2) is expressed as triallelic content with 9, 10, or 12 repeats (StIn2.9, StIn2.10 or StIn2.12). Finally, a single nucleotide polymorphism rs25531 located within the promoter polymorphic-linked region alters the function of the long promoter allele. We developed a PCR-based fragment analysis assay, which is analyzed on an ABI sequencer, whereby we are able to detect all three genotypes simultaneously. Using this technique, we identified novel sequences, which demonstrate promoter repeat regions containing (1) a 17 repeat with rs25531 A/G polymorphism, (2) two with 18-repeat units, (3) one with 20-repeat units and (4) a 24-repeat sequence. The novel repeats were confirmed by direct sequencing of gel-purified amplicons.",
+ "publisher": "Neuroscience letters",
+ "issn": "0304-3940",
+ "date": "2005-10-10",
+ "abstract": "Huntington's disease (HD) is caused by an expanded CAG mutation and may show a heterogeneous clinical presentation. To date, although the age at onset mostly depends on the expanded CAG repeat number, no validated easy-to-test biomarkers exist either for following up patients progression rate or for exactly predicting age at onset (defined as the time when motor clinical manifestations first became noticeable). We tested the function of A(2A) receptor, strongly expressed in the brain striatum and peripheral cells, in patients' blood platelets and confirmed a maximum number of binding sites (B(max)) higher than in controls (216 +/- 9 versus 137 +/- 7; p=0.0001). We found a linear correlation between the receptor B(max) and the expanded CAG repeat number (n=52, r(2)=0.19, p=0.0011). When we selected the patients according to their clinical presentation (according to the predominating motor manifestations) and plotted the receptor B(max) against patients' age at onset, we found a significant linear correlation only when considering those subjects with chorea predominant on all other motor symptoms (n=26, r(2)=0.39, p=0.0007). Because the typical chorea may depend on early dysfunction of the striatum in HD, peripheral A(2A) amplification in blood platelets might reflect a central dysfunction in this part of the brain. Further studies on a larger sample size should confirm whether the analysis of A(2A)-receptor binding in patients' blood could be a useful clinical marker according to the patients' phenotype.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22832606"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16221531"
},
{
- "id": "pmid:21147489",
+ "id": "pmid:16111888",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21147489",
- "title": "The neurology and natural history of patients with indeterminate CAG repeat length mutations of the Huntington disease gene.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/16111888",
+ "title": "Evaluation of the benzothiazole aggregation inhibitors riluzole and PGL-135 as therapeutics for Huntington's disease.",
"type": "article-journal",
- "doi": "10.1016/j.jns.2010.11.015",
+ "doi": "10.1016/j.nbd.2005.07.007",
"authors": [
- ["Peter K", "Panegyres"],
- ["Judy G S", "Goh"]
+ ["Emma", "Hockly"],
+ ["Jamie", "Tse"],
+ ["Amy L", "Barker"],
+ ["Donna L", "Moolman"],
+ ["Jean-Luc", "Beunard"],
+ ["Adrian P", "Revington"],
+ ["Kim", "Holt"],
+ ["Sunny", "Sunshine"],
+ ["Hilary", "Moffitt"],
+ ["Kirupa", "Sathasivam"],
+ ["Benjamin", "Woodman"],
+ ["Erich E", "Wanker"],
+ ["Philip A S", "Lowden"],
+ ["Gillian P", "Bates"]
],
- "publisher": "Journal of the neurological sciences",
- "issn": "1878-5883",
- "date": "2010-12-13",
- "abstract": "This study aims to understand the neurological manifestations of patients with an indeterminate CAG repeat length (36-39) of the Huntingtin gene, HTT.",
+ "publisher": "Neurobiology of disease",
+ "issn": "0969-9961",
+ "date": "2005-08-18",
+ "abstract": "Huntington's disease (HD) is an inherited progressive neurological disorder for which there is no effective therapy. It is caused by a CAG/polyglutamine repeat expansion that leads to abnormal protein aggregation and deposition in the brain. Several compounds have been shown to disrupt the aggregation process in vitro, including a number of benzothiazoles. To further explore the therapeutic potential of the benzothiazole aggregation inhibitors, we assessed PGL-135 and riluzole in hippocampal slice cultures derived from the R6/2 mouse, confirming their ability to inhibit aggregation with an EC50 of 40 microM in this system. Preliminary pharmacological work showed that PGL-135 was metabolically unstable, and therefore, we conducted a preclinical trial in the R6/2 mouse with riluzole. At the maximum tolerated dose, we achieved steady-state riluzole levels of 100 microM in brain. However, this was insufficient to inhibit aggregation in vivo and we found no improvement in the disease phenotype.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21147489"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16111888"
},
{
- "id": "pmid:21106039",
+ "id": "pmid:16096998",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21106039",
- "title": "Functional increase of brain histaminergic signaling in Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/16096998",
+ "title": "Juvenile onset Huntington disease resulting from a very large maternal expansion.",
"type": "article-journal",
- "doi": "10.1111/j.1750-3639.2010.00465.x",
+ "doi": "10.1002/ajmg.a.30891",
"authors": [
- ["Daniel J", "van Wamelen"],
- ["Ling", "Shan"],
- ["N Ahmad", "Aziz"],
- ["Jasper J", "Anink"],
- ["Ai-Min", "Bao"],
- ["Raymund A C", "Roos"],
- ["Dick F", "Swaab"]
+ ["F A", "Nahhas"],
+ ["J", "Garbern"],
+ ["K M", "Krajewski"],
+ ["B B", "Roa"],
+ ["G L", "Feldman"]
],
- "publisher": "Brain pathology (Zurich, Switzerland)",
- "issn": "1750-3639",
- "date": "2010-12-27",
- "abstract": "To evaluate whether central histaminergic signaling in Huntington's disease (HD) patients is affected, we assessed mRNA levels of histidine decarboxylase (HDC), volume of and neuron number in the hypothalamic tuberomamillary nucleus (TMN) (HD n = 8, controls n = 8). In addition, we assessed histamine N-methyltransferase (HMT) and histamine receptor (H(1) R, H(2) R and H(3) R) mRNA levels in the inferior frontal gyrus (IFG) (n = 9 and 9) and caudate nucleus (CN) (n = 6 and 6) by real-time polymerase chain reaction. In HD patients, TMN volume and neuronal number was unaltered (P = 0.72, P = 0.25). The levels of HDC mRNA (P = 0.046), IFG HMT (P < 0.001), H(1) R (P < 0.001) and H(3) R mRNA levels (P = 0.011) were increased, while CN H(2) R and H(3) R mRNA levels were decreased (P = 0.041, P = 0.009). In HD patients, we observed a positive correlation between IFG H(3) R mRNA levels and CAG repeat length (P = 0.024) and negative correlations between age at onset of disease and IFG HMT (P = 0.015) and H(1) R (P = 0.021) mRNA levels. These findings indicate a functional increase in brain histaminergic signaling in HD, and provide a rationale for the use of histamine receptor antagonists.",
+ "publisher": "American journal of medical genetics. Part A",
+ "issn": "1552-4825",
+ "date": "2005-09-01",
+ "abstract": "We report a 5(1/2)-year-old girl with a maternal family history of Huntington disease (HD), who presented clinically with unbalanced gait, impaired speech, and increasing difficulty with fine motor control. Onset of symptoms began at the age of 3(1/2) years. The suspected diagnosis of juvenile HD, based upon her family history, was confirmed by DNA analysis. At age 7, the patient died secondary to complications of her underlying disorder. Juvenile-onset Huntington disease is uncommon, predominantly transmitted by fathers and is always associated with very large expansions of the CAG repeat. Interestingly, this patient inherited a large CAG size expansion from her mother, who herself had symptoms of HD at the age of 18. Molecular analysis revealed that the mother had 70 CAG repeats whereas our patient had approximately 130 CAG repeats. This is the largest reported CAG expansion from a maternal transmission that has been confirmed molecularly and it demonstrates that very large expansions can also occur through the maternal lineage.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21106039"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16096998"
},
{
- "id": "pmid:21068430",
+ "id": "pmid:16082690",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21068430",
- "title": "Tapping linked to function and structure in premanifest and symptomatic Huntington disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/16082690",
+ "title": "Family-based association study of serotonin transporter gene polymorphisms in attention deficit hyperactivity disorder: no evidence for association in UK and Taiwanese samples.",
"type": "article-journal",
- "doi": "10.1212/wnl.0b013e3182020123",
+ "doi": "10.1002/ajmg.b.30203",
"authors": [
- ["N", "Bechtel"],
- ["R I", "Scahill"],
- ["H D", "Rosas"],
- ["T", "Acharya"],
- ["S J A", "van den Bogaard"],
- ["C", "Jauffret"],
- ["M J", "Say"],
- ["A", "Sturrock"],
- ["H", "Johnson"],
- ["C E", "Onorato"],
- ["D H", "Salat"],
- ["A", "Durr"],
- ["B R", "Leavitt"],
- ["R A C", "Roos"],
- ["G B", "Landwehrmeyer"],
- ["D R", "Langbehn"],
- ["J C", "Stout"],
- ["S J", "Tabrizi"],
- ["R", "Reilmann"]
+ ["Xiaohui", "Xu"],
+ ["Jonathan", "Mill"],
+ ["Chi-Ken", "Chen"],
+ ["Keeley", "Brookes"],
+ ["Eric", "Taylor"],
+ ["Philip", "Asherson"]
],
- "publisher": "Neurology",
- "issn": "1526-632X",
- "date": "2010-11-10",
- "abstract": "Motor signs are functionally disabling features of Huntington disease. Characteristic motor signs define disease manifestation. Their severity and onset are assessed by the Total Motor Score of the Unified Huntington's Disease Rating Scale, a categorical scale limited by interrater variability and insensitivity in premanifest subjects. More objective, reliable, and precise measures are needed which permit clinical trials in premanifest populations. We hypothesized that motor deficits can be objectively quantified by force-transducer-based tapping and correlate with disease burden and brain atrophy.",
+ "publisher": "American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics",
+ "issn": "1552-4841",
+ "date": "2005-11-05",
+ "abstract": "Five independent studies have reported associations between serotonin transporter gene (5-HTT) polymorphisms and attention deficit hyperactivity disorder (ADHD). Four studies found evidence for association between the long-allele of a 44-base pair insertion/deletion polymorphism (5-HTTLPR), one of the studies found association to a variable number tandem repeat within intron 2, another to the T-allele of a single base pair substitution in the 3'-untranslated regions and another reported preferential transmission of a haplotype of the three markers (long-allele/10-repeat-allele/T-allele). One further study found no evidence for these associations. We investigated the association of these three markers in two samples of ADHD patients from the United Kingdom (n = 197) and Taiwan (n = 212), using within-family tests of association. No association was found between any of the three markers in either of the two populations. Although we found some evidence for the preferential transmission of a rare haplotype (long-allele/9-repeat-allele/T-allele; chi2 = 4.5, P = 0.034), we concluded that this most likely occurred by chance factors alone.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21068430"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16082690"
},
{
- "id": "pmid:20935170",
+ "id": "pmid:15986189",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/20935170",
- "title": "Huntington's and myotonic dystrophy hESCs: down-regulated trinucleotide repeat instability and mismatch repair machinery expression upon differentiation.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15986189",
+ "title": "Association study of a novel functional polymorphism of the serotonin transporter gene in bipolar disorder and suicidal behaviour.",
"type": "article-journal",
- "doi": "10.1093/hmg/ddq456",
+ "doi": "10.1007/s00213-005-0046-z",
"authors": [
- ["Anna", "Seriola"],
- ["Claudia", "Spits"],
- ["Jodie P", "Simard"],
- ["Pierre", "Hilven"],
- ["Patrick", "Haentjens"],
- ["Christopher E", "Pearson"],
- ["Karen", "Sermon"]
+ ["Vincenzo", "De Luca"],
+ ["Subi", "Tharmalingam"],
+ ["Nicole", "King"],
+ ["John", "Strauss"],
+ ["Natalie", "Bulgin"],
+ ["James L", "Kennedy"]
],
- "publisher": "Human molecular genetics",
- "issn": "1460-2083",
- "date": "2010-10-08",
- "abstract": "Huntington's disease (HD) and myotonic dystrophy (DM1) are caused by trinucleotide repeat expansions. The repeats show different instability patterns according to the disorder, cell type and developmental stage. Here we studied the behavior of these repeats in DM1- and HD-derived human embryonic stem cells (hESCs) before and after differentiation, and its relationship to the DNA mismatch repair (MMR). The relatively small (CAG)44 HD expansion was stable in undifferentiated and differentiated HD hESCs. In contrast, the DM1 repeat showed instability from the earliest passages onwards in DM1 hESCs with (CTG)250 or (CTG)1800. Upon differentiation the DM1 repeat was stabilized. MMR genes, including hMSH2, hMSH3 and hMSH6 were assessed at the transcript and protein levels in differentiated cells. The coincidence of differentiation-induced down-regulated MMR expression with reduced instability of the long expanded repeats in hESCs is consistent with a known requirement of MMR proteins for repeat instability in transgenic mice. This is the first demonstration of a correlation between altered repeat instability of an endogenous DM1 locus and natural MMR down-regulation, in contrast to the commonly used murine knock-down systems.",
+ "publisher": "Psychopharmacology",
+ "issn": "0033-3158",
+ "date": "2005-09-29",
+ "abstract": "A serotonin transporter gene linked polymorphic region (5-HTTLPR) has been investigated in several genetic association studies, including studies of bipolar disorder (BD) and suicidality. The current study was designed to examine whether the new long (A/G) variant polymorphism of the 5-HTT gene may be associated with the suicide attempts in 305 families with at least one member having BD. No association with history of suicide attempt was found either in the multiallelic HTTLPR (LRS=0.15, df=2, P=0.92), or with the intron 2 variable number tandem repeat (VNTR) polymorphism (LRS=0.87 df=2 P=0.64). When we performed a haplotype analysis, we found no association between suicide attempt and haplotype distribution (LRS=1.84 df=4 P=0.76). These findings suggest that this new polymorphism in the 5-HTT gene may not influence suicidal behaviour in patients with bipolar disorder.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20935170"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15986189"
},
{
- "id": "pmid:20919768",
+ "id": "pmid:15954918",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/20919768",
- "title": "Neurocognitive signs in prodromal Huntington disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15954918",
+ "title": "Interleukin-1 gene cluster polymorphisms predict risk of ESRD.",
"type": "article-journal",
- "doi": "10.1037/a0020937",
+ "doi": "10.1111/j.1523-1755.2005.00403.x",
"authors": [
- ["Julie C", "Stout"],
- ["Jane S", "Paulsen"],
- ["Sarah", "Queller"],
- ["Andrea C", "Solomon"],
- ["Kathryn B", "Whitlock"],
- ["J Colin", "Campbell"],
- ["Noelle", "Carlozzi"],
- ["Kevin", "Duff"],
- ["Leigh J", "Beglinger"],
- ["Douglas R", "Langbehn"],
- ["Shannon A", "Johnson"],
- ["Kevin M", "Biglan"],
- ["Elizabeth H", "Aylward"]
+ ["James B", "Wetmore"],
+ ["Adriana M", "Hung"],
+ ["David H", "Lovett"],
+ ["Saunak", "Sen"],
+ ["Omer", "Quershy"],
+ ["Kirsten L", "Johansen"]
],
- "publisher": "Neuropsychology",
- "issn": "1931-1559",
- "date": "2011-01-01",
- "abstract": "PREDICT-HD is a large-scale international study of people with the Huntington disease (HD) CAG-repeat expansion who are not yet diagnosed with HD. The objective of this study was to determine the stage in the HD prodrome at which cognitive differences from CAG-normal controls can be reliably detected.",
+ "publisher": "Kidney international",
+ "issn": "0085-2538",
+ "date": "2005-07-01",
+ "abstract": "Patients with chronic kidney disease manifest an inflammatory state relative to healthy individuals. Inflammation is regulated in part by genes of the interleukin-1 (IL-1) gene cluster. We hypothesized that polymorphisms in this gene cluster may be associated with risk of end-stage renal disease (ESRD).",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20919768"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15954918"
},
{
- "id": "pmid:24868381",
+ "id": "pmid:15906159",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/24868381",
- "title": "A case of juvenile huntington disease in a 6-year-old boy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15906159",
+ "title": "Early changes in Huntington's disease patient brains involve alterations in cytoskeletal and synaptic elements.",
"type": "article-journal",
- "doi": "10.14802/jmd.10012",
+ "doi": "10.1007/s11068-004-0514-8",
"authors": [
- ["Jun-Sang", "Sunwoo"],
- ["Soon-Tae", "Lee"],
- ["Manho", "Kim"]
+ ["Nicholas A", "DiProspero"],
+ ["Er-Yun", "Chen"],
+ ["Vinod", "Charles"],
+ ["Markus", "Plomann"],
+ ["Jeffrey H", "Kordower"],
+ ["Danilo A", "Tagle"]
],
- "publisher": "Journal of movement disorders",
- "issn": "2005-940X",
- "date": "2010-10-30",
- "abstract": "Huntington disease is a neurodegenerative disorder distinguished by the triad of dominant inheritance, choreoathetosis and dementia, usually with onset in the fourth and fifth decades. It is caused by an unstable cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the gene IT15 in locus 4p16.3. Juvenile HD that constitutes about 3% to 10% of all patients is clinically different from adult-onset form and characterized by a larger number of CAG repeats typically exceeding 60. We report a case of a 6-year-old boy with myoclonic seizure and 140 CAG repeats confirmed by molecular genetic analysis.",
+ "publisher": "Journal of neurocytology",
+ "issn": "0300-4864",
+ "date": "2004-09-01",
+ "abstract": "Huntington's disease (HD) is caused by a polyglutamine repeat expansion in the N-terminus of the huntingtin protein. Huntingtin is normally present in the cytoplasm where it may interact with structural and synaptic elements. The mechanism of HD pathogenesis remains unknown but studies indicate a toxic gain-of-function possibly through aberrant protein interactions. To investigate whether early degenerative changes in HD involve alterations of cytoskeletal and vesicular components, we examined early cellular changes in the frontal cortex of HD presymptomatic (PS), early pathological grade (grade 1) and late-stage (grade 3 and 4) patients as compared to age-matched controls. Morphologic analysis using silver impregnation revealed a progressive decrease in neuronal fiber density and organization in pyramidal cell layers beginning in presymptomatic HD cases. Immunocytochemical analyses for the cytoskeletal markers alpha -tubulin, microtubule-associated protein 2, and phosphorylated neurofilament demonstrated a concomitant loss of staining in early grade cases. Immunoblotting for synaptic proteins revealed a reduction in complexin 2, which was marked in some grade 1 HD cases and significantly reduced in all late stage cases. Interestingly, we demonstrate that two synaptic proteins, dynamin and PACSIN 1, which were unchanged by immunoblotting, showed a striking loss by immunocytochemistry beginning in early stage HD tissue suggesting abnormal distribution of these proteins. We propose that mutant huntingtin affects proteins involved in synaptic function and cytoskeletal integrity before symptoms develop which may influence early disease onset and/or progression.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24868381"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15906159"
},
{
- "id": "pmid:20688164",
+ "id": "pmid:15832309",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/20688164",
- "title": "Cerebral cortex structure in prodromal Huntington disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15832309",
+ "title": "Ancient origin of the CAG expansion causing Huntington disease in a Spanish population.",
"type": "article-journal",
- "doi": "10.1016/j.nbd.2010.07.014",
+ "doi": "10.1002/humu.20167",
"authors": [
- ["Peggy C", "Nopoulos"],
- ["Elizabeth H", "Aylward"],
- ["Christopher A", "Ross"],
- ["Hans J", "Johnson"],
- ["Vincent A", "Magnotta"],
- ["Andrew R", "Juhl"],
- ["Ronald K", "Pierson"],
- ["James", "Mills"],
- ["Douglas R", "Langbehn"],
- ["Jane S", "Paulsen"]
+ ["Javier", "Garc\u00eda-Planells"],
+ ["Juan A", "Burguera"],
+ ["Pilar", "Sol\u00eds"],
+ ["Jos\u00e9 M", "Mill\u00e1n"],
+ ["Dami\u00e1n", "Ginestar"],
+ ["Francesc", "Palau"],
+ ["Carmen", "Espin\u00f3s"]
],
- "publisher": "Neurobiology of disease",
- "issn": "1095-953X",
- "date": "2010-08-02",
- "abstract": "Neuroimaging studies of subjects who are gene-expanded for Huntington Disease, but not yet diagnosed (termed prodromal HD), report that the cortex is \"spared,\" despite the decrement in striatal and cerebral white-matter volume. Measurement of whole-cortex volume can mask more subtle, but potentially clinically relevant regional changes in volume, thinning, or surface area. The current study addressed this limitation by evaluating cortical morphology of 523 prodromal HD subjects. Participants included 693 individuals enrolled in the PREDICT-HD protocol. Of these participants, 523 carried the HD gene mutation (prodromal HD group); the remaining 170 were non gene-expanded and served as the comparison group. Based on age and CAG repeat length, gene-expanded subjects were categorized as \"Far from onset,\" \"Midway to onset,\" \"Near onset,\" and \"already diagnosed.\" MRI scans were processed using FreeSurfer. Cortical volume, thickness, and surface area were not significantly different between the Far from onset group and controls. However, beginning in the Midway to onset group, the cortex showed significant volume decrement, affecting most the posterior and superior cerebral regions. This pattern progressed when evaluating the groups further into the disease process. Areas that remained mostly unaffected included ventral and medial regions of the frontal and temporal cortex. Morphologic changes were mostly in thinning as surface area did not substantially change in most regions. Early in the course of HD, the cortex shows changes that are manifest as cortical thinning and are most robust in the posterior and superior regions of the cerebrum.",
+ "publisher": "Human mutation",
+ "issn": "1098-1004",
+ "date": "2005-05-01",
+ "abstract": "Huntington disease (HD) is an autosomal dominant neurodegenerative disorder characterized clinically by progressive motor impairment, cognitive decline, and emotional deterioration. The disease is caused by the abnormal expansion of a CAG trinucleotide repeat in the first exon of the huntingtin gene in chromosome 4p16.3. HD is spread worldwide and it is generally accepted that few mutational events account for the origin of the pathogenic CAG expansion in most populations. We have investigated the genetic history of HD mutation in 83 family probands from the Land of Valencia, in Eastern Spain. An analysis of the HD/CCG repeat in informative families suggested that at least two main chromosomes were associated in the Valencian population, one associated with allele 7 (77 mutant chromosomes) and one associated with allele 10 (two mutant chromosomes). Haplotype A-7-A (H1) was observed in 47 out of 48 phase-known mutant chromosomes, obtained by segregation analysis, through the haplotype analysis of rs1313770-HD/CCG-rs82334, as it also was in 120 out of 166 chromosomes constructed by means of the PHASE program. The genetic history and geographical distribution of the main haplotype H1 were both studied by constructing extended haplotypes with flanking short tandem repeats (STRs) D4S106 and D4S3034. We found that we were able to determine the age of the CAG expansion associated with the haplotype H1 as being between 4,700 and 10,000 years ago. Furthermore, we observed a nonhomogenous distribution in the different regions associated with the different extended haplotypes of the ancestral haplotype H1, suggesting that local founder effects have occurred.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20688164"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15832309"
},
{
- "id": "pmid:20655708",
+ "id": "pmid:15811941",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/20655708",
- "title": "Association of serotonin transporter promoter (5-HTTLPR) and intron 2 (VNTR-2) polymorphisms with treatment response in temporal lobe epilepsy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15811941",
+ "title": "RNA interference improves motor and neuropathological abnormalities in a Huntington's disease mouse model.",
"type": "article-journal",
- "doi": "10.1016/j.eplepsyres.2010.06.008",
+ "doi": "10.1073/pnas.0501507102",
"authors": [
- ["Hrvoje", "Hecimovic"],
- ["Jasminka", "Stefulj"],
- ["Lipa", "Cicin-Sain"],
- ["Vida", "Demarin"],
- ["Branimir", "Jernej"]
+ ["Scott Q", "Harper"],
+ ["Patrick D", "Staber"],
+ ["Xiaohua", "He"],
+ ["Steven L", "Eliason"],
+ ["In\u00eas H", "Martins"],
+ ["Qinwen", "Mao"],
+ ["Linda", "Yang"],
+ ["Robert M", "Kotin"],
+ ["Henry L", "Paulson"],
+ ["Beverly L", "Davidson"]
],
- "publisher": "Epilepsy research",
- "issn": "1872-6844",
- "date": "2010-07-23",
- "abstract": "Temporal lobe epilepsy (TLE) is the most common epilepsy and about 30% of patients have poorly controlled seizures. Neurobiology underlying responsiveness to medical treatment in TLE patients is unclear and there are currently no biological tests to predict course of the disease. Animal and human studies repeatedly suggested serotonergic dysfunction in subjects with TLE. We investigated association of serotonin transporter (5-HTT) gene polymorphisms with medical treatment response in patients with TLE.",
+ "publisher": "Proceedings of the National Academy of Sciences of the United States of America",
+ "issn": "0027-8424",
+ "date": "2005-04-05",
+ "abstract": "Huntington's disease (HD) is a fatal, dominant neurogenetic disorder. HD results from polyglutamine repeat expansion (CAG codon, Q) in exon 1 of HD, conferring a toxic gain of function on the protein huntingtin (htt). Currently, no preventative treatment exists for HD. RNA interference (RNAi) has emerged as a potential therapeutic tool for treating dominant diseases by directly reducing disease gene expression. Here, we show that RNAi directed against mutant human htt reduced htt mRNA and protein expression in cell culture and in HD mouse brain. Importantly, htt gene silencing improved behavioral and neuropathological abnormalities associated with HD. Our data provide support for the further development of RNAi for HD therapy.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20655708"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15811941"
},
{
- "id": "pmid:20645403",
+ "id": "pmid:15764008",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/20645403",
- "title": "Tongue force analysis assesses motor phenotype in premanifest and symptomatic Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15764008",
+ "title": "Yugoslav HD phenocopies analyzed on the presence of mutations in PrP, ferritin, and Jp-3 genes.",
"type": "article-journal",
- "doi": "10.1002/mds.23243",
+ "doi": "10.1080/00207450590519571",
"authors": [
- ["Ralf", "Reilmann"],
- ["Stefan", "Bohlen"],
- ["Thomas", "Klopstock"],
- ["Andreas", "Bender"],
- ["Adolf", "Weindl"],
- ["Philipp", "Saemann"],
- ["Dorothee P", "Auer"],
- ["E Bernd", "Ringelstein"],
- ["Herwig W", "Lange"]
+ ["Milica", "Keckarevi\u0107"],
+ ["Dusanka", "Savi\u0107"],
+ ["Marina", "Svetel"],
+ ["Vladimir", "Kosti\u0107"],
+ ["Slobodanka", "Vukosavi\u0107"],
+ ["Stanka", "Romac"]
],
- "publisher": "Movement disorders : official journal of the Movement Disorder Society",
- "issn": "1531-8257",
- "date": "2010-10-15",
- "abstract": "Motor symptoms in Huntington's Disease (HD) are commonly assessed by the Unified Huntington's Disease Rating Scale-Total Motor Score (UHDRS-TMS). However, the UHDRS-TMS is limited by interrater variability, its categorical nature, and insensitivity in premanifest subjects. More objective and quantitative measures of motor phenotype may complement the use of the UHDRS-TMS as outcome measure and increase the power and sensitivity of clinical trials. Deficits in tongue protrusion are well acknowledged in HD and constitute a subitem of the UHDRS-TMS. We, therefore, investigated whether objective and quantitative assessment of tongue protrusion forces (TPF) provides measures that (1) correlate to the severity of motor phenotype detected in the UHDRS-TMS in symptomatic HD, (2) detect a motor phenotype in premanifest HD gene-carriers, and (3) exhibit a correlation to the genotype as assessed by a disease burden score (based on CAG-repeat length and age). Using a precalibrated force transducer, the ability of premanifest gene carriers (n = 15) and subjects with symptomatic HD (n = 20) to generate and maintain isometric TPF at three target force levels (0.25, 0.5, and 1.0 N) was assessed and compared with age-matched controls (n = 20) in a cross-sectional study. Measures of variability of TPF and tongue contact time distinguished controls, premanifest, and symptomatic HD groups and correlated to the UHDRS-TMS and disease burden score, suggesting a strong genotype-phenotype correlation. Group distinction was most reliable at the lowest target force level. We conclude that assessment of TPF may be a useful objective and quantitative marker of motor dysfunction in premanifest and symptomatic HD.",
+ "publisher": "The International journal of neuroscience",
+ "issn": "0020-7454",
+ "date": "2005-02-01",
+ "abstract": "Huntington disease (HD) is a well-defined autosomal dominant neurodegenerative disease caused by CAG repeat expansions in HD gene. There are a significant number of HD cases where this mutation was not found and such cases are named HD-like phenotype (HDL). This article reports 48 patients with HDL phenotype. Patients were analyzed on the presence of mutations in prion (PrP), ferritin and junctophilin-3 (JP-3) genes. None of the patients showed the presence of the mutation in analyzed genes. This could suggest that there is some other gene/genes where the mutation can cause the disease with clinical features of HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20645403"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15764008"
},
{
- "id": "pmid:20552561",
+ "id": "pmid:15716522",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/20552561",
- "title": "Synthesis of pathological and nonpathological human exon 1 huntingtin.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15716522",
+ "title": "Incidence and mutation rates of Huntington's disease in Spain: experience of 9 years of direct genetic testing.",
"type": "article-journal",
- "doi": "10.1002/psc.1252",
+ "doi": "10.1136/jnnp.2004.036806",
"authors": [
- ["David", "Singer"],
- ["Thomas", "Zauner"],
- ["Maika", "Genz"],
- ["Ralf", "Hoffmann"],
- ["Thole", "Zuchner"]
+ ["M A", "Ramos-Arroyo"],
+ ["S", "Moreno"],
+ ["A", "Valiente"]
],
- "publisher": "Journal of peptide science : an official publication of the European Peptide Society",
- "issn": "1099-1387",
- "date": "2010-07-01",
- "abstract": "Huntington's disease (HD) is a neurodegenerative disorder that affects approximately 1 in 10 000 individuals. The underlying gene mutation was identified as a CAG-triplet repeat expansion in the gene huntingtin. The CAG sequence codes for glutamine, and in HD, an expansion of the polyglutamine (poly-Q) stretch above 35 glutamine residues results in pathogenicity. It has been demonstrated in various animal models that only the expression of exon 1 huntingtin, a 67-amino acid-long polypeptide plus a variable poly-Q stretch, is sufficient to cause full HD-like pathology. Therefore, a deeper understanding of exon 1 huntingtin, its structure, aggregation mechanism and interaction with other proteins is crucial for a better understanding of the disease. Here, we describe the synthesis of a 109-amino acid-long exon 1 huntingtin peptide including a poly-Q stretch of 42 glutamines. This microwave-assisted solid phase peptide synthesis resulted in milligram amounts of peptide with high purity. We also synthesized a nonpathogenic version of exon 1 huntingtin (90-amino acid long including a poly-Q stretch of 23 glutamine residues) using the same strategy. In circular dichroism spectroscopy, both polypeptides showed weak alpha-helical properties with the longer peptide showing a higher helical degree. These model peptides have great potential for further biomedical analyses, e.g. for large-scale pre-screenings for aggregation inhibitors, further structural analyses as well as protein-protein interaction studies.",
+ "publisher": "Journal of neurology, neurosurgery, and psychiatry",
+ "issn": "0022-3050",
+ "date": "2005-03-01",
+ "abstract": "Prior to the discovery of the Huntington's disease (HD) mutation, the prevalence, incidence, and new mutation rates for this disease were based on the presence of progressive choreic movements and a positive family history.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20552561"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15716522"
},
{
- "id": "pmid:20457230",
+ "id": "pmid:15704211",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/20457230",
- "title": "Longitudinal analysis of the behavioural phenotype in Hdh(CAG)150 Huntington's disease knock-in mice.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15704211",
+ "title": "Mitochondrial impairment in patients and asymptomatic mutation carriers of Huntington's disease.",
"type": "article-journal",
- "doi": "10.1016/j.brainresbull.2010.05.004",
+ "doi": "10.1002/mds.20373",
"authors": [
- ["Simon", "Brooks"],
- ["Gemma", "Higgs"],
- ["Lesley", "Jones"],
- ["Stephen B", "Dunnett"]
+ ["Carsten", "Saft"],
+ ["Jochen", "Zange"],
+ ["J\u00fcrgen", "Andrich"],
+ ["Klaus", "M\u00fcller"],
+ ["Katrin", "Lindenberg"],
+ ["Bernhard", "Landwehrmeyer"],
+ ["Matthias", "Vorgerd"],
+ ["Peter H", "Kraus"],
+ ["Horst", "Przuntek"],
+ ["Ludger", "Sch\u00f6ls"]
],
- "publisher": "Brain research bulletin",
- "issn": "1873-2747",
- "date": "2010-05-08",
- "abstract": "In people with Huntington's disease, an expanded CAG repeat sequence on the HTT gene confers a toxic gain function resulting in a progressive and fatal neurodegeneration. The Hdh((CAG)Q150) Huntington's disease mouse line is a knock-in model of the disease that carries \u223c150 CAG repeats on the normal mouse Htt locus. To determine that these mice are a useful model of the disease, they were assessed longitudinally for motor and cognitive deficits relevant to the human disease state. Each test was conducted bi-monthly across the lifespan of the animal. The results indicate that the Hdh(Q150/Q150) mice were impaired on each of the measures used, with deficits appearing on a 3-stage water maze test at 4 months of age and on prepulse inhibition at 6 months of age, both of which were prior to the manifestation of motor abnormalities. Grip strength, as measured by the inverted cage lid test, was reduced in the Hdh(Q150/Q150) mice from 10 months of age, when the male mice also exhibited weight loss relative to their wildtype littermates. On the accelerating rotarod, deficits in the carrier mice did not appear until they were 21 months old. Our results demonstrate that the Hdh((CAG)150) is a valid model of HD that displays early and progressive cognitive deficits that precede the onset of motor abnormalities.",
+ "publisher": "Movement disorders : official journal of the Movement Disorder Society",
+ "issn": "0885-3185",
+ "date": "2005-06-01",
+ "abstract": "Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the IT-15 gene; however, it remains unknown how the mutation leads to selective neurodegeneration. Several lines of evidence suggest impaired mitochondrial function as a component of the neurodegenerative process in HD. We assessed energy metabolism in the skeletal muscle of 15 HD patients and 12 asymptomatic mutation carriers in vivo using 31P magnetic resonance spectroscopy. Phosphocreatine recovery after exercise is a direct measure of ATP synthesis and was slowed significantly in HD patients and mutation carriers in comparison to age- and gender-matched healthy controls. We found that oxidative function is impaired to a similar extent in manifest HD patients and asymptomatic mutation carriers. Our findings suggest that mitochondrial dysfunction is an early and persistent component of the pathophysiology of HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20457230"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15704211"
},
{
- "id": "pmid:20385209",
+ "id": "pmid:15635668",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/20385209",
- "title": "Striatal and white matter predictors of estimated diagnosis for Huntington disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15635668",
+ "title": "Serotonin transporter intron 2 polymorphism associated with rigid-compulsive behaviors in Dutch individuals with pervasive developmental disorder.",
"type": "article-journal",
- "doi": "10.1016/j.brainresbull.2010.04.003",
+ "doi": "10.1002/ajmg.b.30122",
"authors": [
- ["Jane S", "Paulsen"],
- ["Peggy C", "Nopoulos"],
- ["Elizabeth", "Aylward"],
- ["Christopher A", "Ross"],
- ["Hans", "Johnson"],
- ["Vincent A", "Magnotta"],
- ["Andrew", "Juhl"],
- ["Ronald K", "Pierson"],
- ["James", "Mills"],
- ["Douglas", "Langbehn"],
- ["Martha", "Nance"]
+ ["Erik J", "Mulder"],
+ ["George M", "Anderson"],
+ ["Ido P", "Kema"],
+ ["Astrid M", "Brugman"],
+ ["Cees E J", "Ketelaars"],
+ ["Annelies", "de Bildt"],
+ ["Natasja D J", "van Lang"],
+ ["Johan A", "den Boer"],
+ ["Ruud B", "Minderaa"]
],
- "publisher": "Brain research bulletin",
- "issn": "1873-2747",
- "date": "2010-04-10",
- "abstract": "Previous MRI studies with participants prior to manifest Huntington disease have been conducted in small single-site samples. The current study reports data from a systematic multi-national study during the prodromal period of Huntington disease and examines whether various brain structures make unique predictions about the proximity to manifest disease. MRI scans were acquired from 657 participants enrolled at 1 of 32 PREDICT-HD research sites. Only prodromal Huntington disease participants (those not meeting motor criteria for diagnosis) were included and subgrouped by estimated diagnosis proximity (Near, Mid, and Far) based upon a formula incorporating age and CAG-repeat length. Results show volumes of all three subgroups differed significantly from Controls for total brain tissue, cerebral spinal fluid, white matter, cortical gray matter, thalamus, caudate, and putamen. Total striatal volume demonstrated the largest differences between Controls and all three prodromal subgroups. Cerebral white matter offered additional independent power in the prediction of estimated proximity to diagnosis. In conclusion, this large cross-sectional study shows that changes in brain volume are detectable years to decades prior to estimated motor diagnosis of Huntington disease. This suggests that a clinical trial of a putative neuroprotective agent could begin as much as 15 years prior to estimated motor diagnosis in a cohort of persons at risk for but not meeting clinical motor diagnostic criteria for Huntington disease, and that neuroimaging (striatal and white matter volumes) may be among the best predictors of diagnosis proximity.",
+ "publisher": "American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics",
+ "issn": "1552-4841",
+ "date": "2005-02-05",
+ "abstract": "Two putatively functional polymorphisms of the serotonin transporter gene (HTT, SLC6A4) were examined for associations with risk for pervasive developmental disorders (PDDs) and specific autism phenotypes. Dutch patients diagnosed with PDD (N = 125, age range 5-20 years, DSM-IV-TR based criteria, ADI-R and ADOS behavioral assessments) and their parents (N = 230) were genotyped for promoter ins/del (5-HTTLPR) and intron 2 variable number of tandem repeats (VNTR) alleles. Using the transmission disequilibrium test (TDT), no disorder-specific preferential transmission of promoter (long and short) or intron 2 (10- and 12-repeat) alleles was observed. However, multivariate analysis of continuous autism-related behavioral measures revealed that subjects with intron 2 12/12 genotype were significantly more impaired in the rigid-compulsive domain (P = 0.008). Quantitative TDT (QTDT) analysis also showed significant association of the intron 2 VNTR 12-repeat allele with rigid-compulsive behavior (P = 0.015). These results suggest that intron 2 VNTR alleles or nearby polymorphisms in linkage disequilibrium may play a role in specific aspects of the behavioral phenotype of autism.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20385209"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15635668"
},
{
- "id": "pmid:20145031",
+ "id": "pmid:15468075",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/20145031",
- "title": "Late-onset Huntington disease with intermediate CAG repeats: true or false?",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15468075",
+ "title": "Huntington's Disease-like 2 (HDL2) in North America and Japan.",
"type": "article-journal",
- "doi": "10.1136/jnnp.2008.170902",
+ "doi": "10.1002/ana.20248",
"authors": [
- ["Justus L", "Groen"],
- ["Rob M A", "de Bie"],
- ["Elisabeth M J", "Foncke"],
- ["Raymund A C", "Roos"],
- ["Klaus L", "Leenders"],
- ["Marina A J", "Tijssen"]
+ ["Russell L", "Margolis"],
+ ["Susan E", "Holmes"],
+ ["Adam", "Rosenblatt"],
+ ["Lisa", "Gourley"],
+ ["Elizabeth", "O'Hearn"],
+ ["Christopher A", "Ross"],
+ ["William K", "Seltzer"],
+ ["Ruth H", "Walker"],
+ ["Tetsuo", "Ashizawa"],
+ ["Astrid", "Rasmussen"],
+ ["Michael", "Hayden"],
+ ["Elisabeth W", "Almqvist"],
+ ["Juliette", "Harris"],
+ ["Stanley", "Fahn"],
+ ["Marcy E", "MacDonald"],
+ ["Jayalakshmi", "Mysore"],
+ ["Takayoshi", "Shimohata"],
+ ["Shoji", "Tsuji"],
+ ["Nicholas", "Potter"],
+ ["Kazuhiro", "Nakaso"],
+ ["Yoshiki", "Adachi"],
+ ["Kenji", "Nakashima"],
+ ["Thomas", "Bird"],
+ ["Amanda", "Krause"],
+ ["Penny", "Greenstein"]
],
- "publisher": "Journal of neurology, neurosurgery, and psychiatry",
- "issn": "1468-330X",
- "date": "2010-02-01",
- "abstract": "Huntington disease (HD) is a neurodegenerative disorder associated with an expanded CAG trinucleotide repeat length in the huntingtin gene. 'Intermediate alleles' with 27 to 35 CAG repeats generally do not cause HD but are unstable upon germ-line transmission. Insights in CAG repeat mosaicism and enhanced trinucleotide expansion in postmitotic neurons indicate that in the intermediate range, other factors than the CAG repeat length in diagnostic tests have to be considered. Here, we report two patients with mild, late onset HD and an intermediate repeat allele. The authors anticipate that intermediate repeats can cause late-onset HD due to disease modifiers and may be more common than previously stated.",
+ "publisher": "Annals of neurology",
+ "issn": "0364-5134",
+ "date": "2004-11-01",
+ "abstract": "Huntington's Disease-like 2 (HDL2) is a progressive, autosomal dominant, neurodegenerative disorder with marked clinical and pathological similarities to Huntington's disease (HD). The causal mutation is a CTG/CAG expansion mutation on chromosome 16q24.3, in a variably spliced exon of junctophilin-3. The frequency of HDL2 was determined in nine independent series of patients referred for HD testing or selected for the presence of an HD-like phenotype in North America or Japan. The repeat length, ancestry, and age of onset of all North American HDL2 cases were determined. The results show that HDL2 is very rare, with a frequency of 0 to 15% among patients in the nine case series with an HD-like presentation who do not have the HD mutation. HDL2 is predominantly, and perhaps exclusively, found in individuals of African ancestry. Repeat expansions ranged from 44 to 57 triplets, with length instability in maternal transmission detected in a repeat of r2=0.29, p=0.0098). The results further support the evidence that the repeat expansion at the chromosome 16q24.3 locus is the direct cause of HDL2 and provide preliminary guidelines for the genetic testing of patients with an HD-like phenotype.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20145031"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15468075"
},
{
- "id": "pmid:20001119",
+ "id": "pmid:15372528",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/20001119",
- "title": "Disrupted temporal control in the R6/2 mouse model of Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15372528",
+ "title": "Mosaicism of the CAG repeat sequence in the Huntington disease gene in a pair of monozygotic twins.",
"type": "article-journal",
- "doi": "10.1037/a0017650",
+ "doi": "10.1002/ajmg.a.30128",
"authors": [
- ["Fuat", "Balci"],
- ["Mark", "Day"],
- ["Aislinn", "Rooney"],
- ["Dani", "Brunner"]
+ ["Anne", "N\u00f8rrem\u00f8lle"],
+ ["Lis", "Hasholt"],
+ ["Cathrine Bie", "Petersen"],
+ ["Hans", "Eiberg"],
+ ["Steen G", "Hasselbalch"],
+ ["Peter", "Gideon"],
+ ["J\u00f8rgen E", "Nielsen"],
+ ["Sven Asger", "S\u00f8rensen"]
],
- "publisher": "Behavioral neuroscience",
- "issn": "1939-0084",
- "date": "2009-12-01",
- "abstract": "Huntington's disease is characterized by corticostriatal dysfunction and degeneration of the striatum with progressive loss of the medium spiny neurons. These circuits are important for instrumental responding, interval timing, and temporal control over motor output. We investigated the acquisition of timed operant responding in two R6/2 Huntington's Disease models, differing in CAG repeat length and genetic background (115 and 250 CAG repeats, and a mixed CBAxC57 or pure C57 background) and their corresponding wild type controls using the peak procedure. Both mouse lines exhibited similar response control deficits. In unreinforced peak trials, mice either did not learn to terminate an ongoing response past reinforcement time or required more trials to acquisition compared to the wild type mice. While transgenic and wild type mice did not exhibit differences in temporal accuracy, response curves were flatter in transgenic mice, suggesting decreased temporal control over operant responding. The results are discussed in terms of the neurobiology of interval timing, instrumental responding, and the neuropathology of HD and R6/2 mice.",
+ "publisher": "American journal of medical genetics. Part A",
+ "issn": "1552-4825",
+ "date": "2004-10-01",
+ "abstract": "We report on a pair of monozygotic twins belonging to a family segregating Huntington disease (HD). In routine DNA analysis of blood cells, they displayed three alleles of the CAG repeat sequence in the HD gene. Two different cell lines, carrying the normal allele together with either an expanded allele with 47 CAGs or an intermediate allele with 37 CAGs, were detected in blood and buccal epithelium from both twins. To our knowledge, this is the first case described of HD gene CAG repeat length mosaicism in blood cells. Haplotype analysis established that the 37 CAG allele most likely arose by contraction of the maternal 47 CAG allele. The contraction must have taken place postzygotically, possibly at a very early stage of development, and probably before separation of the twins. One of the twins has presented symptoms of HD for 4 years; his skin fibroblasts and hair roots carried only the cell line with the 47 CAG repeat allele. The other twin, who is without symptoms at present, displayed mosaicism in skin fibroblasts and hair roots. If the proportion of the two cell lines in the brain of each twin resembles that of their hair roots (another tissue originating from the ectoderm), the mosaicism in the unaffected twin would mean that only a part of his brain cells carried the expanded allele, which could explain why he, in contrast to his brother, has no symptoms at this time.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20001119"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15372528"
},
{
- "id": "pmid:19997493",
+ "id": "pmid:15345132",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/19997493",
- "title": "Stoichiometry of base excision repair proteins correlates with increased somatic CAG instability in striatum over cerebellum in Huntington's disease transgenic mice.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15345132",
+ "title": "In vitro proliferation and expansion of hematopoietic progenitors present in mobilized peripheral blood from normal subjects and cancer patients.",
"type": "article-journal",
- "doi": "10.1371/journal.pgen.1000749",
+ "doi": "10.1089/scd.2004.13.382",
"authors": [
- ["Agathi-Vassiliki", "Goula"],
- ["Brian R", "Berquist"],
- ["David M", "Wilson"],
- ["Vanessa C", "Wheeler"],
- ["Yvon", "Trottier"],
- ["Karine", "Merienne"]
+ ["Guadalupe", "Mart\u00ednez-Jaramillo"],
+ ["Patricia", "Flores-Guzm\u00e1n"],
+ ["Juan Jos\u00e9", "Montesinos"],
+ ["Sandra", "Quintana"],
+ ["Javier", "Bautista"],
+ ["Elizabeth", "S\u00e1nchez-Valle"],
+ ["Mar\u00eda", "de Jes\u00fas Nambo"],
+ ["Hector", "Mayani"]
],
- "publisher": "PLoS genetics",
- "issn": "1553-7404",
- "date": "2009-12-04",
- "abstract": "Huntington's disease (HD) is a progressive neurodegenerative disorder caused by expansion of an unstable CAG repeat in the coding sequence of the Huntingtin (HTT) gene. Instability affects both germline and somatic cells. Somatic instability increases with age and is tissue-specific. In particular, the CAG repeat sequence in the striatum, the brain region that preferentially degenerates in HD, is highly unstable, whereas it is rather stable in the disease-spared cerebellum. The mechanisms underlying the age-dependence and tissue-specificity of somatic CAG instability remain obscure. Recent studies have suggested that DNA oxidation and OGG1, a glycosylase involved in the repair of 8-oxoguanine lesions, contribute to this process. We show that in HD mice oxidative DNA damage abnormally accumulates at CAG repeats in a length-dependent, but age- and tissue-independent manner, indicating that oxidative DNA damage alone is not sufficient to trigger somatic instability. Protein levels and activities of major base excision repair (BER) enzymes were compared between striatum and cerebellum of HD mice. Strikingly, 5'-flap endonuclease activity was much lower in the striatum than in the cerebellum of HD mice. Accordingly, Flap Endonuclease-1 (FEN1), the main enzyme responsible for 5'-flap endonuclease activity, and the BER cofactor HMGB1, both of which participate in long-patch BER (LP-BER), were also significantly lower in the striatum compared to the cerebellum. Finally, chromatin immunoprecipitation experiments revealed that POLbeta was specifically enriched at CAG expansions in the striatum, but not in the cerebellum of HD mice. These in vivo data fit a model in which POLbeta strand displacement activity during LP-BER promotes the formation of stable 5'-flap structures at CAG repeats representing pre-expanded intermediate structures, which are not efficiently removed when FEN1 activity is constitutively low. We propose that the stoichiometry of BER enzymes is one critical factor underlying the tissue selectivity of somatic CAG expansion.",
+ "publisher": "Stem cells and development",
+ "issn": "1547-3287",
+ "date": "2004-08-01",
+ "abstract": "In the present study, we have assessed, in a comparative manner, the in vitro proliferation and expansion potentials of hematopoietic progenitor cells (HPC) present in mobilized peripheral blood from normal subjects (MPB-n; n = 18) and cancer patients (MPB-c; n = 18). The latter included patients with breast cancer (BrCa; n = 8), Hodgkin disease (HD; n = 4), non-Hodgkin lymphoma (NHL; n = 3), and acute myeloid leukemia (AML; n = 3). Progenitor cells from normal bone marrow (BM) and umbilical cord blood (UCB) were included as controls. HPC, enriched by a negative selection procedure, were cultured for 25 days, in serum-free liquid media in the presence of a cytokine combination including early- and late-acting cytokines. Our results demonstrate that the in vitro biological properties of progenitor cells present in MPB differ, depending on whether they are derived from healthy individuals, from patients with solid tumors, or from patients with hematological neoplasias. Among all cell sources analyzed, UCB-derived progenitors showed the greatest proliferation and expansion potentials (1000-fold increase in total cell numbers on day 15, and a 22-fold increase in myeloid progenitor cell numbers, at day 10). Progenitor cells present in MPB from hematologically normal individuals showed proliferation and expansion potentials comparable to those of HPC from normal BM (500-fold increase in total cell numbers on day 15, and a 14-fold increase in myeloid progenitor cell numbers, at day 10). The proliferation/expansion potentials of MPB progenitors from BrCa patients were also within the normal range, although in the lower levels (327-fold increase in total cell numbers, on day 15, and 11.8-fold increase in myeloid progenitors, at day 10). In contrast, progenitors present in MPB from patients with HD, NHL, and especially AML, showed reduced in vitro capacities (119-, 102-, and 51-fold increase in total cell numbers, respectively; and 8-, 4-, and 2.6-fold increase in myeloid progenitor cells, respectively). To our knowledge, this is the first report in which the in vitro proliferation and expansion potentials of HPC from MPB from normal subjects and cancer patients are assessed simultaneously in a comparative manner.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19997493"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15345132"
},
{
- "id": "pmid:19857538",
+ "id": "pmid:15254954",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/19857538",
- "title": "The hOGG1 Ser326Cys polymorphism and Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15254954",
+ "title": "Markedly asymmetrical parkinsonism as a leading feature of adult-onset Huntington's disease.",
"type": "article-journal",
- "doi": "10.1016/j.tox.2009.10.019",
+ "doi": "10.1002/mds.20093",
"authors": [
- ["Fabio", "Copped\u00e8"],
- ["Francesca", "Migheli"],
- ["Roberto", "Ceravolo"],
- ["Elisa", "Bregant"],
- ["Anna", "Rocchi"],
- ["Lucia", "Petrozzi"],
- ["Elisa", "Unti"],
- ["Renata", "Lonigro"],
- ["Gabriele", "Siciliano"],
- ["Lucia", "Migliore"]
+ ["Shih-Ching", "Wang"],
+ ["Guey-Jen", "Lee-Chen"],
+ ["Cheng-Kung", "Wang"],
+ ["Chiung-Mei", "Chen"],
+ ["Lok-Ming", "Tang"],
+ ["Yih-Ru", "Wu"]
],
- "publisher": "Toxicology",
- "issn": "1879-3185",
- "date": "2009-10-24",
- "abstract": "Increasing evidence supports a role for oxidative DNA damage and impaired DNA repair mechanisms in the pathogenesis of age related neurodegenerative diseases. Within this context there is a current interest in the understanding of the role played by polymorphisms of DNA repair genes in the inter-individual risk to develop neurodegenerative pathologies, as well as in the onset and the progression of disease symptoms. Particularly, somatic CAG repeat expansion of the gene encoding for huntingtin has been observed in tissues of patients affected by Huntington's disease (HD), including blood and brain. Recent evidence suggests that somatic CAG repeat expansion in HD cells might contribute to disease age at onset and is mediated by the DNA repair OGG1 enzyme, during the removal of 8-oxoguanine (8-oxoG) from the DNA. There is also evidence that the expression of hMTH1, which removes 8-oxoG from the nucleotide pool, protects mice from HD-like symptoms, and progenitor striatal cells from the toxic effects of the mutant huntingtin. The hOGG1 Ser326Cys polymorphism results in reduced OGG1 activity and increased 8-oxoG formation. In the present study, performed on blood DNA from 91 HD subjects, we observed that bearers of the mutant Cys326 allele (Ser326Cys+Cys326Cys) tend to have an increased number of CAG repeats of the expanded HD allele (P=0.049); moreover bearers of at least one copy of the mutant Cys326 allele, mainly heterozygous subjects, showed a significant (P=0.041) earlier disease onset than Ser326Ser wild-type individuals, suggesting a possible role of the hOGG1 Ser326Cys polymorphism in HD phenotype.",
+ "publisher": "Movement disorders : official journal of the Movement Disorder Society",
+ "issn": "0885-3185",
+ "date": "2004-07-01",
+ "abstract": "We report on a 28-year-old man who presented with right hand tremor, bradykinesia, and rigidity of his right side extremities. Our case report emphasizes that markedly asymmetrical parkinsonism can be an initial presentation of adult-onset Huntington's disease (HD), and different clinical presentations can be observed in members of an individual HD family with the same CAG repeat length.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19857538"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15254954"
},
{
- "id": "pmid:19823894",
+ "id": "pmid:15147313",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/19823894",
- "title": "Magnetization transfer imaging in 'premanifest' Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15147313",
+ "title": "Dendritic spine pathology and deficits in experience-dependent dendritic plasticity in R6/1 Huntington's disease transgenic mice.",
"type": "article-journal",
- "doi": "10.1007/s00415-009-5339-4",
+ "doi": "10.1111/j.0953-816x.2004.03374.x",
"authors": [
- ["Caroline K", "Jurgens"],
- ["Reineke", "Bos"],
- ["Jasper", "Luyendijk"],
- ["Marie-No\u00eblle W", "Witjes-An\u00e9"],
- ["Jeroen", "van der Grond"],
- ["Huub A M", "Middelkoop"],
- ["Raymund A C", "Roos"]
+ ["Tara L", "Spires"],
+ ["Helen E", "Grote"],
+ ["Sylvia", "Garry"],
+ ["Patricia M", "Cordery"],
+ ["Anton", "Van Dellen"],
+ ["Colin", "Blakemore"],
+ ["Anthony J", "Hannan"]
],
- "publisher": "Journal of neurology",
- "issn": "1432-1459",
- "date": "2009-10-13",
- "abstract": "To investigate whether magnetization transfer imaging (MTI) is a useful detector of diffuse brain abnormalities in 'premanifest' carriers of the Huntington's disease (HD) gene mutation. Furthermore we examined the relations between MTI, clinical measures and CAG repeat length. Sixteen premanifest carriers of the HD gene without motor manifestation and 14 non-carriers underwent a clinical evaluation and a MRI scan. MTI analysis of whole brain, grey matter and white matter was performed producing magnetization transfer ratio (MTR) histograms. A lower peak height of the grey matter MTR histogram in carriers was significantly associated with more UHDRS motor abnormalities. Furthermore, a lower peak height of the whole brain, grey and white matter was strongly associated with a longer CAG repeat length. MTI measures themselves did not differ significantly between carriers and non-carriers. In premanifest HD mutation carriers, a lower MTR peak height, reflecting worse histological brain composition, was related to subtle motor abnormalities and higher CAG repeat length. Although we could not detect altered MTI characteristics in carriers of the HD gene mutation without clinical manifestations, we did provide evidence that the MTR peak height might reflect genetic and subclinical disease burden and may be of value in monitoring further disease progression and provide insight in clinical heterogeneity.",
+ "publisher": "The European journal of neuroscience",
+ "issn": "0953-816X",
+ "date": "2004-05-01",
+ "abstract": "Huntington's disease (HD) is a fatal neurodegenerative disease caused by a CAG repeat expansion coding for an expanded polyglutamine tract in the huntingtin protein. Dendritic abnormalities occur in human HD patients and in several transgenic mouse models of the disease. In this study, we examine, for the first time, dendrite and spine pathology in the R6/1 mouse model of HD, which mimics neurodegeneration seen in human HD. Enriching the environment of HD transgenic mice delays the onset of symptoms, so we also examine the effects of enrichment on dendrite pathology. Golgi-impregnated tissue from symptomatic R6/1 HD mice reveals a decrease in dendritic spine density and dendritic spine length in striatal medium spiny neurons and cortical pyramidal neurons. HD also causes a specific reduction in the proportion of bifurcated dendritic spines on basal dendrites of cortical pyramidal neurons. No differences in soma size, recurving distal dendrites, or dendritic branching were observed. Although home-cage environmental enrichment from 1 to 8 months of age increases spine density in wild-type mice, it has no effect on the spine pathology in HD mice. These results show that dendritic spine pathology in R6/1 HD mice resembles degenerative changes seen in human HD and in other transgenic mouse models of the disease. We thus provide further evidence that the HD mutation disrupts the connectivity in both neostriatum and cerebral cortex, which will contribute to motor and cognitive disease symptoms. Furthermore, we demonstrate that Huntington's disease pathology interferes with the normal plastic response of dendritic spines to environmental enrichment.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19823894"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15147313"
},
{
- "id": "pmid:19810823",
+ "id": "pmid:15094787",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/19810823",
- "title": "Presymptomatic diagnosis in Huntington's disease: the Mexican experience.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15094787",
+ "title": "Variants of the serotonin transporter gene (SLC6A4) significantly contribute to hyperserotonemia in autism.",
"type": "article-journal",
- "doi": "10.1089/gtmb.2009.0032",
+ "doi": "10.1038/sj.mp.4001409",
"authors": [
- ["Maria Elisa", "Alonso"],
- ["Adriana", "Ochoa"],
- ["Ana Luisa", "Sosa"],
- ["Yaneth", "Rodr\u00edguez"],
- ["Mireya", "Ch\u00e1vez"],
- ["Catherine", "Boll"],
- ["Petra", "Yescas"],
- ["Rosario", "Mac\u00edas"],
- ["Astrid", "Rasmussen"]
+ ["A M", "Coutinho"],
+ ["G", "Oliveira"],
+ ["T", "Morgadinho"],
+ ["C", "Fesel"],
+ ["T R", "Macedo"],
+ ["C", "Bento"],
+ ["C", "Marques"],
+ ["A", "Ata\u00edde"],
+ ["T", "Miguel"],
+ ["L", "Borges"],
+ ["A M", "Vicente"]
],
- "publisher": "Genetic testing and molecular biomarkers",
- "issn": "1945-0257",
- "date": "2009-12-01",
- "abstract": "Huntington's disease (HD) is an autosomal dominant progressive, disabling neurodegenerative disorder, for which there is no effective treatment. Predictive testing (PT) for this illness began in 1986 and by 1993 it became more precise after cloning of the gene and the discovery of a CAG repeat expansion as the underlying cause. The objective of this paper is to illustrate the implementation and results of a PT program in a group of at-risk Mexican individuals with 12 years of follow-up. Our PT program conforms to the guidelines proposed by the International Huntington Association and the HD Working group of the World Federation of Neurology. Seventy-five individuals requested the testing, four of them did not fulfill the inclusion criteria, and five abandoned the program voluntarily before receiving the test results. Therefore, 66 results were delivered to 41 noncarriers and 25 mutation carriers. We did not have any catastrophic event, but 4 individuals with normal results and 11 mutation carriers were depressed. Even if this is a small sample, it is the first report of PT in a Latin-American population in which we have been faced with the same problems referred to in larger series.",
+ "publisher": "Molecular psychiatry",
+ "issn": "1359-4184",
+ "date": "2004-03-01",
+ "abstract": "The role of the serotonin system in the etiology and pathogenesis of autism spectrum disorders (ASD) is not clearly defined. High levels of platelet serotonin (5-HT) have been consistently found in a proportion of patients, and it is known that specific 5-HT transporter gene (SLC6A4) variants modulate transporter reuptake function, therefore possibly influencing the occurrence of hyperserotonemia in a subset of autistic patients. We have examined the association of platelet serotonin levels with two SLC6A4 polymorphisms, 5-HTT gene-linked polymorphic region (HTTLPR) in the promoter and intron 2 variable number of tandem repeats (VNTR), in a sample of 105 ASD patients, their parents, and 52 control children. Quantitative transmission disequilibrium test (QTDT) results showed a significant effect on 5-HT levels of each SLC6A4 marker (P=0.017 for HTTLPR; P=0.047 for intron 2 VNTR) and of haplotypes of the two markers (P=0.017), with a major contribution of the L.Stin2.10 haplotype (P=0.0013). A 5-HT mean value in the range of hyperserotonemia was associated with the homozygous L.Stin2.10 haplotype (H (1,N=97)=7.76, P=0.0054), which occurred in 33% of hyperserotonemic patients against 6% of patients with normal 5-HT levels (Fisher's exact test: P=0.013, OR=8). Allele interaction at the HTTLPR locus was found, with a significant dominance variance effect on 5-HT levels. We found no transmission disequilibrium of any of the SLC6A4 variants in ASD. Our results show that the SLC6A4 gene is a significant factor in the determination of 5-HT levels, and that specific SLC6A4 variants are associated with an increased risk for hyperserotonemia in our sample of autistic patients. The biological mechanism, however, is unlikely to involve the SLC6A4 gene solely. The associated SLC6A4 alleles likely interact with other genes or environmental factors to produce the abnormally high 5-HT levels observed in this subset of autistic patients, who possibly represent a separate etiological group.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19810823"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15094787"
},
{
- "id": "pmid:19621255",
+ "id": "pmid:15076735",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/19621255",
- "title": "Preimplantation genetic diagnosis of P450 oxidoreductase deficiency and Huntington Disease using three different molecular approaches simultaneously.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15076735",
+ "title": "Pseudo-neglect in Huntington's disease correlates with decreased angular gyrus density.",
"type": "article-journal",
- "doi": "10.1007/s10815-009-9327-5",
+ "doi": "10.1097/00001756-200404290-00026",
"authors": [
- ["Trinitat M", "Alberola"],
- ["Rosa", "Bautista-Ll\u00e1cer"],
- ["Esther", "Fern\u00e1ndez"],
- ["Xavier", "Vendrell"],
- ["Manuel", "P\u00e9rez-Alonso"]
+ ["Aileen K", "Ho"],
+ ["Peter J", "Nestor"],
+ ["Guy B", "Williams"],
+ ["John L", "Bradshaw"],
+ ["Barbara J", "Sahakian"],
+ ["Trevor W", "Robbins"],
+ ["Roger A", "Barker"]
],
- "publisher": "Journal of assisted reproduction and genetics",
- "issn": "1573-7330",
- "date": "2009-07-21",
- "abstract": "Description of the confluence of different molecular techniques to detect three different mutations in one cell. The man carries a 20 base pair insertion in exon 12 of the POR gene (c.1551_1552ins20), and the woman carries a point mutation in exon 8 of the POR gene (c.859G>C) plus a triplet repeat expansion in the HTT gene.",
+ "publisher": "Neuroreport",
+ "issn": "0959-4965",
+ "date": "2004-04-29",
+ "abstract": "Visuospatial attentional bias was examined in Huntington's disease (HD) patients with mild disease, asymptomatic gene-positive patients and controls. No group differences were found on the grey scales task (which is a non-motor task of visuospatial attentional bias), although patients' trinucleotide (CAG) repeat length correlated with increasing leftward bias. On the line bisection task, symptomatic patients made significantly larger leftward bisection errors relative to controls, who showed the normal slight degree of leftward error (pseudo-neglect). The asymptomatic group showed a trend for greater leftward error than controls. A subset of participants went on to have structural MRI, which showed a correlation between increased leftward error on the line bisection task and reduced density in the angular gyrus area (BA39) bilaterally. This finding is consistent with recent literature suggesting a critical role for the angular gyrus in the lateralization of visuospatial attention.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19621255"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15076735"
},
{
- "id": "pmid:19607813",
+ "id": "pmid:14993615",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/19607813",
- "title": "Polyglutamine expansion in huntingtin increases its insertion into lipid bilayers.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/14993615",
+ "title": "Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset.",
"type": "article-journal",
- "doi": "10.1016/j.bbrc.2009.07.039",
+ "doi": "10.1073/pnas.0308679101",
"authors": [
- ["Kimberly B", "Kegel"],
- ["Vitali", "Schewkunow"],
- ["Ellen", "Sapp"],
- ["Nicholas", "Masso"],
- ["Erich E", "Wanker"],
- ["Marian", "DiFiglia"],
- ["Wolfgang H", "Goldmann"]
+ ["Nancy S", "Wexler"],
+ ["Judith", "Lorimer"],
+ ["Julie", "Porter"],
+ ["Fidela", "Gomez"],
+ ["Carol", "Moskowitz"],
+ ["Edith", "Shackell"],
+ ["Karen", "Marder"],
+ ["Graciela", "Penchaszadeh"],
+ ["Simone A", "Roberts"],
+ ["Javier", "Gay\u00e1n"],
+ ["Denise", "Brocklebank"],
+ ["Stacey S", "Cherny"],
+ ["Lon R", "Cardon"],
+ ["Jacqueline", "Gray"],
+ ["Stephen R", "Dlouhy"],
+ ["Sandra", "Wiktorski"],
+ ["Marion E", "Hodes"],
+ ["P Michael", "Conneally"],
+ ["Jack B", "Penney"],
+ ["James", "Gusella"],
+ ["Jang-Ho", "Cha"],
+ ["Michael", "Irizarry"],
+ ["Diana", "Rosas"],
+ ["Steven", "Hersch"],
+ ["Zane", "Hollingsworth"],
+ ["Marcy", "MacDonald"],
+ ["Anne B", "Young"],
+ ["J Michael", "Andresen"],
+ ["David E", "Housman"],
+ ["Margot Mieja", "De Young"],
+ ["Ernesto", "Bonilla"],
+ ["Theresa", "Stillings"],
+ ["Americo", "Negrette"],
+ ["S Robert", "Snodgrass"],
+ ["Maria Dolores", "Martinez-Jaurrieta"],
+ ["Maria A", "Ramos-Arroyo"],
+ ["Jacqueline", "Bickham"],
+ ["Juan Sanchez", "Ramos"],
+ ["Frederick", "Marshall"],
+ ["Ira", "Shoulson"],
+ ["Gustavo J", "Rey"],
+ ["Andrew", "Feigin"],
+ ["Norman", "Arnheim"],
+ ["Amarilis", "Acevedo-Cruz"],
+ ["Leticia", "Acosta"],
+ ["Jose", "Alvir"],
+ ["Kenneth", "Fischbeck"],
+ ["Leslie M", "Thompson"],
+ ["Angela", "Young"],
+ ["Leon", "Dure"],
+ ["Christopher J", "O'Brien"],
+ ["Jane", "Paulsen"],
+ ["Adam", "Brickman"],
+ ["Denise", "Krch"],
+ ["Shelley", "Peery"],
+ ["Penelope", "Hogarth"],
+ ["Donald S", "Higgins"],
+ ["Bernhard", "Landwehrmeyer"]
],
- "publisher": "Biochemical and biophysical research communications",
- "issn": "1090-2104",
- "date": "2009-07-14",
- "abstract": "An expanded polyglutamine (Q) tract (>37Q) in huntingtin (htt) causes Huntington disease. Htt associates with membranes and polyglutamine expansion in htt may alter membrane function in Huntington disease through a mechanism that is not known. Here we used differential scanning calorimetry to examine the effects of polyQ expansion in htt on its insertion into lipid bilayers. We prepared synthetic lipid vesicles composed of phosphatidylcholine and phosphatidylethanolamine and tested interactions of htt amino acids 1-89 with 20Q, 32Q or 53Q with the vesicles. GST-htt1-89 with 53Q inserted into synthetic lipid vesicles significantly more than GST-htt1-89 with 20Q or 32Q. We speculate that by inserting more into cell membranes, mutant huntingtin could increase disorder within the lipid bilayer and thereby disturb cellular membrane function.",
+ "publisher": "Proceedings of the National Academy of Sciences of the United States of America",
+ "issn": "0027-8424",
+ "date": "2004-03-01",
+ "abstract": "Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a triplet (CAG) expansion mutation. The length of the triplet repeat is the most important factor in determining age of onset of HD, although substantial variability remains after controlling for repeat length. The Venezuelan HD kindreds encompass 18,149 individuals spanning 10 generations, 15,409 of whom are living. Of the 4,384 immortalized lymphocyte lines collected, 3,989 DNAs were genotyped for their HD alleles, representing a subset of the population at greatest genetic risk. There are 938 heterozygotes, 80 people with variably penetrant alleles, and 18 homozygotes. Analysis of the 83 kindreds that comprise the Venezuelan HD kindreds demonstrates that residual variability in age of onset has both genetic and environmental components. We created a residual age of onset phenotype from a regression analysis of the log of age of onset on repeat length. Familial correlations (correlation +/- SE) were estimated for sibling (0.40 +/- 0.09), parent-offspring (0.10 +/- 0.11), avuncular (0.07 +/- 0.11), and cousin (0.15 +/- 0.10) pairs, suggesting a familial origin for the residual variance in onset. By using a variance-components approach with all available familial relationships, the additive genetic heritability of this residual age of onset trait is 38%. A model, including shared sibling environmental effects, estimated the components of additive genetic (0.37), shared environment (0.22), and nonshared environment (0.41) variances, confirming that approximately 40% of the variance remaining in onset age is attributable to genes other than the HD gene and 60% is environmental.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19607813"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:14993615"
},
{
- "id": "pmid:19595623",
+ "id": "pmid:14713958",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/19595623",
- "title": "Huntington's disease-like and ataxia syndromes: identification of a family with a de novo SCA17/TBP mutation.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/14713958",
+ "title": "Specific caspase interactions and amplification are involved in selective neuronal vulnerability in Huntington's disease.",
"type": "article-journal",
- "doi": "10.1016/j.parkreldis.2009.06.006",
+ "doi": "10.1038/sj.cdd.4401358",
"authors": [
- ["Sara", "Bech"],
- ["Thor", "Petersen"],
- ["Anne", "N\u00f8rrem\u00f8lle"],
- ["Albert", "Gjedde"],
- ["Lise", "Ehlers"],
- ["Hans", "Eiberg"],
- ["Lena E", "Hjermind"],
- ["Lis", "Hasholt"],
- ["Erik", "Lundorf"],
- ["J\u00f8rgen E", "Nielsen"]
+ ["E", "Hermel"],
+ ["J", "Gafni"],
+ ["S S", "Propp"],
+ ["B R", "Leavitt"],
+ ["C L", "Wellington"],
+ ["J E", "Young"],
+ ["A S", "Hackam"],
+ ["A V", "Logvinova"],
+ ["A L", "Peel"],
+ ["S F", "Chen"],
+ ["V", "Hook"],
+ ["R", "Singaraja"],
+ ["S", "Krajewski"],
+ ["P C", "Goldsmith"],
+ ["H M", "Ellerby"],
+ ["M R", "Hayden"],
+ ["D E", "Bredesen"],
+ ["L M", "Ellerby"]
],
- "publisher": "Parkinsonism & related disorders",
- "issn": "1873-5126",
- "date": "2010-01-01",
- "abstract": "The autosomal dominant spinocerebellar ataxias, commonly referred to as SCAs, are clinically and genetically heterogeneous neurodegenerative disorders. Twenty-eight genetic subtypes have been identified, of which 7 are caused by expansion of a CAG trinucleotide repeat that encodes a polyglutamine tract in the respective proteins. SCA17 is caused by a CAG/CAA repeat expansion in the TATA box-binding protein-gene (TBP). In some cases the clinical phenotype of SCA17 overlaps that of Huntington's disease (HD), hence the use of the term Huntington's disease-like. We screened 89 patients with a Huntington's disease-like phenotype without the HD-gene mutation and 178 patients with genetically unclassified cerebellar ataxia for the mutation in TBP. A 33-year old woman presenting with an HD like phenotype with a de novo 54 CAG/CAA repeat expansion was identified. Her normal allele included 38 repeats. The patient's mother and father both carried normal range repeats, 38/38 and 33/39 respectively. Analysis of the repeat structures revealed that the expansion had occurred upon expansion of the longer paternal allele. We conclude that, however rare, SCA17 must be considered as a cause of Huntington's disease-like phenotypes and ataxia syndromes, also in isolated cases.",
+ "publisher": "Cell death and differentiation",
+ "issn": "1350-9047",
+ "date": "2004-04-01",
+ "abstract": "Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder resulting in selective neuronal loss and dysfunction in the striatum and cortex. The molecular pathways leading to the selectivity of neuronal cell death in HD are poorly understood. Proteolytic processing of full-length mutant huntingtin (Htt) and subsequent events may play an important role in the selective neuronal cell death found in this disease. Despite the identification of Htt as a substrate for caspases, it is not known which caspase(s) cleaves Htt in vivo or whether regional expression of caspases contribute to selective neuronal cells loss. Here, we evaluate whether specific caspases are involved in cell death induced by mutant Htt and if this correlates with our recent finding that Htt is cleaved in vivo at the caspase consensus site 552. We find that caspase-2 cleaves Htt selectively at amino acid 552. Further, Htt recruits caspase-2 into an apoptosome-like complex. Binding of caspase-2 to Htt is polyglutamine repeat-length dependent, and therefore may serve as a critical initiation step in HD cell death. This hypothesis is supported by the requirement of caspase-2 for the death of mouse primary striatal cells derived from HD transgenic mice expressing full-length Htt (YAC72). Expression of catalytically inactive (dominant-negative) forms of caspase-2, caspase-7, and to some extent caspase-6, reduced the cell death of YAC72 primary striatal cells, while the catalytically inactive forms of caspase-3, -8, and -9 did not. Histological analysis of post-mortem human brain tissue and YAC72 mice revealed activation of caspases and enhanced caspase-2 immunoreactivity in medium spiny neurons of the striatum and the cortical projection neurons when compared to controls. Further, upregulation of caspase-2 correlates directly with decreased levels of brain-derived neurotrophic factor in the cortex and striatum of 3-month YAC72 transgenic mice and therefore suggests that these changes are early events in HD pathogenesis. These data support the involvement of caspase-2 in the selective neuronal cell death associated with HD in the striatum and cortex.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19595623"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:14713958"
},
{
- "id": "pmid:21048629",
+ "id": "pmid:14708029",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21048629",
- "title": "A survey of (CAG)n repeats causing juvenile Huntington disease in an Iranian family with 4 affected members.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/14708029",
+ "title": "Serotonin transporter gene and autism: a haplotype analysis in an Irish autistic population.",
"type": "article-journal",
- "doi": "",
+ "doi": "10.1038/sj.mp.4001459",
"authors": [
- ["Mehrdokht", "Mazdeh"],
- ["Hamid", "Pour-Jafari"],
- ["Ali", "Ghaleiha"],
- ["Bita", "Pour-Jafari"]
+ ["J", "Conroy"],
+ ["E", "Meally"],
+ ["G", "Kearney"],
+ ["M", "Fitzgerald"],
+ ["M", "Gill"],
+ ["L", "Gallagher"]
],
- "publisher": "Neurosciences (Riyadh, Saudi Arabia)",
- "issn": "1319-6138",
- "date": "2009-07-01",
- "abstract": "Huntington's disease is caused by a trinucleotide repeat expansion (CAG)n in the gene coding for Huntingtin (Htt) and is one of the several polyglutamine diseases. Its physical symptoms occur in a large range of ages, with a mean occurrence in a person's late 40's and early 50's. Almost all references indicated that if the age of onset is below 20 years then it is known as juvenile HD. Our case was an Iranian family with 4 affected siblings (2 sisters and 2 brothers). In addition to 4 affected children, they had 5 normal male progenies. There was no any other case in their family history. The onset age of the disease in our case family was 20 to 25 years. Their parents were unaffected and nonconsanguineous. Analysis of the pathogenic (CAG)n repeat region of the HD gene for the affected members have showed an expansion allele with 46, 50, 46, and 44 repeats in 4 affected siblings. Our results indicated that the age of 20 years maybe is not a stable limit point for all cases of juvenile HD, and perhaps onset ages are related with the CAG repeat sizes in such individuals.",
+ "publisher": "Molecular psychiatry",
+ "issn": "1359-4184",
+ "date": "2004-06-01",
+ "abstract": "The role of the serotonin transporter (5-HTT) in the development of neuropsychiatric disorders has been widely investigated. Two polymorphisms, an insertion/deletion in the promoter region and a 12 repeat allele in a variable nucleotide tandem repeat (VNTR) in intron 2, drive higher expression of the 5-HTT gene. Four studies have shown nominally significant excess transmission of alleles of the 5-HTT gene in autism, while three studies have reported no excess transmission. This present study investigates the role of 5-HTT in the genetically homogenous Irish population. In all, 84 families were genotyped for five polymorphisms (three SNPs, a VNTR and an in/del). The analysis of allele transmissions using the transmission disequilibrium test (TDT) was undertaken and indicated preferential transmission of the short promoter allele (TDT P-value=0.0334). Linkage disequilibrium between markers was calculated and haplotypes were assessed for excess transmission and odds ratios (ORs) to affected children. A number of haplotypes, especially those involving and surrounding SNP10, showed evidence of association. The ORs ranged from 1.2 to 2.4. The most significant haplotype associated with transmission to affected probands was the SNP10-VNTR-SNP18 haplotype (chi(2)=7.3023, P=0.0069, odds ratio=1.8). This haplotype included the 12 repeat allele of the VNTR, which is associated with increased expression and may play a subtle role in the early development of the brain in affected probands.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21048629"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:14708029"
},
{
- "id": "pmid:19484127",
+ "id": "pmid:14581669",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/19484127",
- "title": "Genetic knock-down of HDAC7 does not ameliorate disease pathogenesis in the R6/2 mouse model of Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/14581669",
+ "title": "Huntington's disease: clinical correlates of disability and progression.",
"type": "article-journal",
- "doi": "10.1371/journal.pone.0005747",
+ "doi": "10.1212/01.wnl.0000086373.32347.16",
"authors": [
- ["Caroline L", "Benn"],
- ["Rachel", "Butler"],
- ["Lydia", "Mariner"],
- ["Jude", "Nixon"],
- ["Hilary", "Moffitt"],
- ["Michal", "Mielcarek"],
- ["Ben", "Woodman"],
- ["Gillian P", "Bates"]
+ ["N", "Mahant"],
+ ["E A", "McCusker"],
+ ["K", "Byth"],
+ ["S", "Graham"]
],
- "publisher": "PloS one",
- "issn": "1932-6203",
- "date": "2009-06-01",
- "abstract": "Huntington's disease (HD) is an inherited, progressive neurological disorder caused by a CAG/polyglutamine repeat expansion, for which there is no effective disease modifying therapy. In recent years, transcriptional dysregulation has emerged as a pathogenic process that appears early in disease progression. Administration of histone deacetylase (HDAC) inhibitors such as suberoylanilide hydroxamic acid (SAHA) have consistently shown therapeutic potential in models of HD, at least partly through increasing the association of acetylated histones with down-regulated genes and by correcting mRNA abnormalities. The HDAC enzyme through which SAHA mediates its beneficial effects in the R6/2 mouse model of HD is not known. Therefore, we have embarked on a series of genetic studies to uncover the HDAC target that is relevant to therapeutic development for HD. HDAC7 is of interest in this context because SAHA has been shown to decrease HDAC7 expression in cell culture systems in addition to inhibiting enzyme activity. After confirming that expression levels of Hdac7 are decreased in the brains of wild type and R6/2 mice after SAHA administration, we performed a genetic cross to determine whether genetic reduction of Hdac7 would alleviate phenotypes in the R6/2 mice. We found no improvement in a number of physiological or behavioral phenotypes. Similarly, the dysregulated expression levels of a number of genes of interest were not improved suggesting that reduction in Hdac7 does not alleviate the R6/2 HD-related transcriptional dysregulation. Therefore, we conclude that the beneficial effects of HDAC inhibitors are not predominantly mediated through the inhibition of HDAC7.",
+ "publisher": "Neurology",
+ "issn": "1526-632X",
+ "date": "2003-10-28",
+ "abstract": "To define the phenotypic variation in a large population of patients with Huntington disease (HD) and to identity clinical features that predict disability and the rate of disease progression.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19484127"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:14581669"
},
{
- "id": "pmid:19465745",
+ "id": "pmid:14570710",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/19465745",
- "title": "Somatic expansion of the Huntington's disease CAG repeat in the brain is associated with an earlier age of disease onset.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/14570710",
+ "title": "Dramatic tissue-specific mutation length increases are an early molecular event in Huntington disease pathogenesis.",
"type": "article-journal",
- "doi": "10.1093/hmg/ddp242",
+ "doi": "10.1093/hmg/ddg352",
"authors": [
- ["Meera", "Swami"],
- ["Audrey E", "Hendricks"],
- ["Tammy", "Gillis"],
- ["Tiffany", "Massood"],
- ["Jayalakshmi", "Mysore"],
- ["Richard H", "Myers"],
- ["Vanessa C", "Wheeler"]
+ ["Laura", "Kennedy"],
+ ["Elizabeth", "Evans"],
+ ["Chiung-Mei", "Chen"],
+ ["Lyndsey", "Craven"],
+ ["Peter J", "Detloff"],
+ ["Margaret", "Ennis"],
+ ["Peggy F", "Shelbourne"]
],
"publisher": "Human molecular genetics",
- "issn": "1460-2083",
- "date": "2009-05-23",
- "abstract": "The age of onset of Huntington's disease (HD) is determined primarily by the length of the HD CAG repeat mutation, but is also influenced by other modifying factors. Delineating these modifiers is a critical step towards developing validated therapeutic targets in HD patients. The HD CAG repeat is somatically unstable, undergoing progressive length increases over time, particularly in brain regions that are the targets of neurodegeneration. Here, we have explored the hypothesis that somatic instability of the HD CAG repeat is itself a modifier of disease. Using small-pool PCR, we quantified somatic instability in the cortex region of the brain from a cohort of HD individuals exhibiting phenotypic extremes of young and old disease onset as predicted by the length of their constitutive HD CAG repeat lengths. After accounting for constitutive repeat length, somatic instability was found to be a significant predictor of onset age, with larger repeat length gains associated with earlier disease onset. These data are consistent with the hypothesis that somatic HD CAG repeat length expansions in target tissues contribute to the HD pathogenic process, and support pursuing factors that modify somatic instability as viable therapeutic targets.",
- "language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19465745"
-},
-{
- "id": "pmid:19250382",
- "manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/19250382",
- "title": "4p16.3 haplotype modifying age at onset of Huntington disease.",
- "type": "article-journal",
- "doi": "10.1111/j.1399-0004.2008.01136.x",
- "authors": [
- ["A", "N\u00f8rrem\u00f8lle"],
- ["E", "Budtz-J\u00f8rgensen"],
- ["K", "Fenger"],
- ["J E", "Nielsen"],
- ["S A", "S\u00f8rensen"],
- ["L", "Hasholt"]
- ],
- "publisher": "Clinical genetics",
- "issn": "1399-0004",
- "date": "2009-03-01",
- "abstract": "Huntington disease (HD) is caused by an expanded CAG repeat sequence in the HD gene. Although the age at onset is correlated to the CAG repeat length, this correlation only explains approximately half of the variation in onset age. Less variation between siblings indicates that the variation is, in part, explained by genetic modifiers. We analyzed polymorphic loci within or close to the HD gene on the HD chromosome in Danish HD patients. We found one specific haplotype segregating with later age at onset, compared with patients with similar CAG repeat length and another haplotype. The nine Danish families in the study carrying this haplotype most likely have a common founder. Several of the polymorphic loci displayed alleles that may be specific to the late-onset haplotype, implicating that from this study we cannot determine which of the loci tested (or other polymorphic loci in this chromosomal area) do in fact contain genetic modifiers of age at onset.",
+ "issn": "0964-6906",
+ "date": "2003-10-21",
+ "abstract": "Huntington disease is caused by the expansion of a CAG repeat encoding an extended glutamine tract in a protein called huntingtin. Although the mutant protein is widely expressed, the earliest and most striking neuropathological changes are observed in the striatum. Here we show dramatic mutation length increases (gains of up to 1000 CAG repeats) in human striatal cells early in the disease course, most likely before the onset of pathological cell loss. Studies of knock-in HD mouse models indicate that the size of the initial CAG repeat mutation may influence both onset and tissue-specific patterns of age-dependent, expansion-biased mutation length variability. Given that CAG repeat length strongly correlates with clinical severity, we suggest that somatic increases of mutation length may play a major role in the progressive nature and cell-selective aspects of both adult-onset and juvenile-onset HD pathogenesis and we discuss the implications of this interpretation of the data presented.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19250382"
-},
-{
- "id": "pmid:19249009",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/19249009",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:19249009']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:14570710"
},
{
- "id": "pmid:21415933",
+ "id": "pmid:12886033",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21415933",
- "title": "Diffusion Tensor Imaging in Preclinical Huntington's Disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/12886033",
+ "title": "Association study of serotonin transporter gene VNTR polymorphism and mood disorders, onset age and suicide attempts in a Chinese sample.",
"type": "article-journal",
- "doi": "10.1007/s11682-008-9051-2",
+ "doi": "10.1159/000071821",
"authors": [
- ["Vincent A", "Magnotta"],
- ["Jinsuh", "Kim"],
- ["Tim", "Koscik"],
- ["Leigh J", "Beglinger"],
- ["Daisy", "Espinso"],
- ["Doug", "Langbehn"],
- ["Peg", "Nopoulos"],
- ["Jane S", "Paulsen"]
+ ["Feng-Chang", "Yen"],
+ ["Chen-Jee", "Hong"],
+ ["Sheu-Jane", "Hou"],
+ ["Jiunn-Kae", "Wang"],
+ ["Shih-Jen", "Tsai"]
],
- "publisher": "Brain imaging and behavior",
- "issn": "1931-7565",
- "date": "2009-03-01",
- "abstract": "Diffusion tensor imaging was used to study brain related changes in white matter that may be associated with Huntington's Disease progression. Thirty-one preclinical gene-mutation carriers were imaged cross-sectionally using diffusion tensor and anatomical brain imaging. Subjects were individuals who had a known gene mutation for HD but did not manifest motor diagnostic criteria for HD. Fractional anisotropy scalar maps showed a positive correlation with five year probability of diagnosis (based upon gene repeat length and current age) in the putamen and a negative correlation in the external capsule. This study shows that scalar maps generated from diffusion tensor imaging may be directly related to the earliest stages of disease progression within HD, even before a diagnosis is given. Findings suggest that DTI measures, therefore, may have the ability to act as a biomarker for disease progression in clinical trials of pre-manifest subjects.",
+ "publisher": "Neuropsychobiology",
+ "issn": "0302-282X",
+ "date": "2003-01-01",
+ "abstract": "The human serotonin transporter (5-HTT) gene is an important candidate for the pathogenesis of mood disorders. Associations have been reported between a variable-number tandem-repeat polymorphism in intron 2 of the serotonin transporter gene (5-HTTVNTR) and mood disorders in a number of studies of Western and Chinese populations. However, no such relationships have been determined in other analogous research. To replicate these positive findings in a Chinese population and to determine the association between onset age of bipolar disorder and 5-HTTVNTR, we investigated the prevalence of this polymorphism in an independent Chinese population (83 bipolar disorder patients, 77 major depressive disorder patients and 169 controls), demonstrating no significant association between the 5-HTTVNTR polymorphism and mood disorders or age at onset. Further, no association was demonstrated between this polymorphism and suicidal history in mood disorder patients. These negative findings suggest that 5-HTTVNTR does not play a major role in the pathogenesis of mood disorder in Chinese populations.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21415933"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12886033"
},
{
- "id": "pmid:19200361",
+ "id": "pmid:12850791",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/19200361",
- "title": "PGC-1alpha as modifier of onset age in Huntington disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/12850791",
+ "title": "Expansion of EBV latent membrane protein 2a specific cytotoxic T cells for the adoptive immunotherapy of EBV latency type 2 malignancies: influence of recombinant IL12 and IL15.",
"type": "article-journal",
- "doi": "10.1186/1750-1326-4-10",
+ "doi": "10.1080/14653240310001262",
"authors": [
- ["Elahe", "Taherzadeh-Fard"],
- ["Carsten", "Saft"],
- ["J\u00fcrgen", "Andrich"],
- ["Stefan", "Wieczorek"],
- ["Larissa", "Arning"]
+ ["H-J", "Wagner"],
+ ["U", "Sili"],
+ ["B", "Gahn"],
+ ["S", "Vigouroux"],
+ ["M H", "Huls"],
+ ["W", "Xie"],
+ ["D", "Vignali"],
+ ["M K", "Brenner"],
+ ["H E", "Heslop"],
+ ["C M", "Rooney"]
],
- "publisher": "Molecular neurodegeneration",
- "issn": "1750-1326",
- "date": "2009-02-06",
- "abstract": "Although there is a strong correlation between CAG repeat length and age at onset (AO) of motor symptoms, individual Huntington disease (HD) patients may differ dramatically in onset age and disease manifestations despite similar CAG repeat lengths. This has led to a search for genetic factors that influence AO. In order to identify such a genetic modifier, we analysed polymorphisms in the PGC-1alpha gene. Recent data indicate inhibition of PGC-1alpha function by mutant Htt supporting a link between transcriptional deregulation and mitochondrial dysfunction in HD. In > 400 HD patients, a polymorphism located within intron 2, a potential recombination hot spot, explains a small, but statistically significant, amount of the variability in AO. Our data suggest that PGC-1alpha has modifying effects on the pathogenic process in HD.",
+ "publisher": "Cytotherapy",
+ "issn": "1465-3249",
+ "date": "2003-01-01",
+ "abstract": "EBV-associated malignancies with a Type II latency gene expression pattern, such as EBV-positive HD, or nasopharyngeal carcinoma, frequently express the EBV latency Ag LMP2a. Hence, they provide a potential target for adoptive immunotherapy using in vitro-generated LMP2a-specific cytotoxic T lymphocytes (CTL). In this study, LMP2a-specific CTL were specifically amplified and the influence of rIL12 and rIL15 on the culture outcome was tested.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19200361"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12850791"
},
{
- "id": "pmid:19193881",
+ "id": "pmid:12824708",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/19193881",
- "title": "Decreased BDNF levels are a major contributor to the embryonic phenotype of huntingtin knockdown zebrafish.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/12824708",
+ "title": "DNA testing for Huntington disease in the Turkish population.",
"type": "article-journal",
- "doi": "10.1523/jneurosci.6039-08.2009",
+ "doi": "10.1159/000070854",
"authors": [
- ["Heike", "Diekmann"],
- ["Oleg", "Anichtchik"],
- ["Angeleen", "Fleming"],
- ["Marie", "Futter"],
- ["Paul", "Goldsmith"],
- ["Alan", "Roach"],
- ["David C", "Rubinsztein"]
+ ["Fahri", "Akbas"],
+ ["Nihan", "Erginel-Unaltuna"]
],
- "publisher": "The Journal of neuroscience : the official journal of the Society for Neuroscience",
- "issn": "1529-2401",
- "date": "2009-02-04",
- "abstract": "Huntington's disease (HD) is an autosomal dominant, neurodegenerative condition caused by a CAG trinucleotide repeat expansion that is translated into an abnormally long polyglutamine tract in the protein huntingtin. Genetic and transgenic studies suggest that the mutation causes disease predominantly via gain-of-function mechanisms. However, loss of normal huntingtin function resulting from the polyglutamine expansion might also contribute to the pathogenesis of HD. Here, we have studied the effects of huntingtin knockdown in zebrafish using morpholino antisense oligonucleotides, as its huntingtin orthologue has 70% amino acid identity with the human protein. Reduced huntingtin levels did not impact on gastrulation and early development, but caused massive apoptosis of neuronal cells by 24 hpf. This was accompanied by impaired neuronal development, resulting in small eyes and heads and enlargement of brain ventricles. Older huntingtin knockdown fish developed lower jaw abnormalities with most branchial arches missing. Molecular analysis revealed that BDNF expression was reduced by approximately 50%. Reduction of BDNF levels by injection of a BDNF morpholino resulted in phenotypes very similar to those seen in huntingtin knockdown zebrafish. The phenotypes of both huntingtin- and BDNF-knockdown zebrafish showed significant rescue when treated with exogenous BDNF protein. This underscores the physiological importance of huntingtin as a regulator of BDNF production and suggests that loss of BDNF is a major cause of the developmental abnormalities seen with huntingtin knockdown in zebrafish. Increasing BDNF expression may represent a useful strategy for Huntington's disease treatment.",
+ "publisher": "European neurology",
+ "issn": "0014-3022",
+ "date": "2003-01-01",
+ "abstract": "Huntington disease (HD) is an autosomal dominant inherited disease, characterized by involuntary movements, behavioral and personality changes and dementia. Although the mean age at onset is about 40 years, onset varies from 5 to 79 years. Therefore, at-risk individuals are never sure to have escaped the disease. The genetic defect is a CAG trinucleotide repeat expansion at the 5' end of the IT-15 gene on chromosome 4. In this study, we analyzed 127 patients with HD and 122 healthy controls. The numbers of CAG repeats varied from 38 to 78 (median: 42) in 127 HD patients, while in healthy controls we observed only 10-35 CAG repeats (median: 18). The length of the CAG repeat expansion in Turkish HD patients and normal controls was similar to that reported from other populations. Negative correlations (r = -0.67) were also found between age of disease onset and repeat length.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19193881"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12824708"
},
{
- "id": "pmid:19133136",
+ "id": "pmid:12782968",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/19133136",
- "title": "The gene coding for PGC-1alpha modifies age at onset in Huntington's Disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/12782968",
+ "title": "No evidence of association of two 5HT transporter gene polymorphisms and attention deficit hyperactivity disorder.",
"type": "article-journal",
- "doi": "10.1186/1750-1326-4-3",
+ "doi": "10.1097/01.ypg.0000056177.32550.a5",
"authors": [
- ["Patrick", "Weydt"],
- ["Selma M", "Soyal"],
- ["Cinzia", "Gellera"],
- ["Stefano", "Didonato"],
- ["Claus", "Weidinger"],
- ["Hannes", "Oberkofler"],
- ["G Bernhard", "Landwehrmeyer"],
- ["Wolfgang", "Patsch"]
+ ["Kate", "Langley"],
+ ["Antony", "Payton"],
+ ["Marian L", "Hamshere"],
+ ["Helen M", "Pay"],
+ ["Deborah C", "Lawson"],
+ ["Darko", "Turic"],
+ ["William", "Ollier"],
+ ["Jane", "Worthington"],
+ ["Michael J", "Owen"],
+ ["Michael C", "O'Donovan"],
+ ["Anita", "Thapar"]
],
- "publisher": "Molecular neurodegeneration",
- "issn": "1750-1326",
- "date": "2009-01-08",
- "abstract": "Huntington's disease (HD) is one of the most common autosomal dominant inherited, neurodegenerative disorders. It is characterized by progressive motor, emotional and cognitive dysfunction. In addition metabolic abnormalities such as wasting and altered energy expenditure are increasingly recognized as clinical hallmarks of the disease. HD is caused by an unstable CAG repeat expansion in the HD gene (HTT), localized on chromosome 4p16.3. The number of CAG repeats in the HD gene is the main predictor of disease-onset, but the remaining variation is strongly heritable. Transcriptional dysregulation, mitochondrial dysfunction and enhanced oxidative stress have been implicated in the pathogenesis. Recent studies suggest that PGC-1alpha, a transcriptional master regulator of mitochondrial biogenesis and metabolism, is defective in HD. A genome wide search for modifier genes of HD age-of-onset had suggested linkage at chromosomal region 4p16-4p15, near the locus of PPARGC1A, the gene coding for PGC-1alpha. We now present data of 2-loci PPARGC1A block 2 haplotypes, showing an effect upon age-at-onset in 447 unrelated HD patients after statistical consideration of CAG repeat lengths in both HTT alleles. Block 1 haplotypes were not associated with the age-at-onset. Homozygosity for the 'protective' block 2 haplotype was associated with a significant delay in disease onset. To our knowledge this is the first study to show clinically relevant effects of the PGC-1alpha system on the course of Huntington's disease in humans.",
+ "publisher": "Psychiatric genetics",
+ "issn": "0955-8829",
+ "date": "2003-06-01",
+ "abstract": "Three studies to date have found evidence (or a trend for evidence) of linkage and association between the long allele of the 44 base pair repeat insertion/deletion 5-HTT functional polymorphism (5-HTTLPR) and attention deficit hyperactivity disorder (ADHD). In an attempt to replicate these findings, we examined this polymorphism and a variable number tandem repeat in the second intron of 5-HTT for association with ADHD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19133136"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12782968"
},
{
- "id": "pmid:19014073",
+ "id": "pmid:12599191",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/19014073",
- "title": "Association study of serotonin transporter gene polymorphisms with obstructive sleep apnea syndrome in Chinese Han population.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/12599191",
+ "title": "Sudden infant death syndrome: association with a promoter polymorphism of the serotonin transporter gene.",
"type": "article-journal",
- "doi": "10.1093/sleep/31.11.1535",
+ "doi": "10.1002/ajmg.a.20005",
"authors": [
- ["Weihua", "Yue"],
- ["Huiguo", "Liu"],
- ["Jishui", "Zhang"],
- ["Xianghui", "Zhang"],
- ["Xiaoping", "Wang"],
- ["Tieqiao", "Liu"],
- ["Pozi", "Liu"],
- ["Wei", "Hao"]
+ ["Debra E", "Weese-Mayer"],
+ ["Elizabeth M", "Berry-Kravis"],
+ ["Brion S", "Maher"],
+ ["Jean M", "Silvestri"],
+ ["Mark E", "Curran"],
+ ["Mary L", "Marazita"]
],
- "publisher": "Sleep",
- "issn": "0161-8105",
- "date": "2008-11-01",
- "abstract": "Since the serotonin (5-HT) is associated with circadian rhythm and breathing regulation, the serotonin transporter (5-HTT), which plays an important role in serotoninergic transmission, might be a strong candidate gene in the pathogenesis of obstructive sleep apnea syndrome (OSAS).",
+ "publisher": "American journal of medical genetics. Part A",
+ "issn": "1552-4825",
+ "date": "2003-03-15",
+ "abstract": "Serotonergic receptor binding in the arcuate nucleus, n. raph\u00e9 obscurus, and other medullary regions is decreased in sudden infant death syndrome (SIDS) cases. Further, a variable tandem repeat sequence polymorphism in the promoter region of the serotonin transporter protein (5-HTT) gene has recently been associated with risk of SIDS in a Japanese cohort. This polymorphism differentially regulates 5-HTT expression, with the long allele (L), the SIDS-associated allele, being a more effective promoter than the short allele (S). We therefore investigated the 5-HTT promoter polymorphism in a cohort of 87 SIDS cases (43 African American and 44 Caucasian) and gender/ethnicity-matched controls. Significant positive associations were found between SIDS and the 5-HTT genotype distribution (P = 0.022), specifically with the L/L genotype (P = 0.048), and between SIDS and the 5-HTT L allele (P = 0.005). There was also a significant negative association between SIDS and the S/S genotype (P = 0.011). The comparisons were repeated in the African American and Caucasian subgroups. The data patterns were consistent in the subgroups, i.e., the L/L genotype and L allele were increased in the cases, but not all subgroup comparisons were statistically significant. These results indicate a relationship between SIDS and the L allele of the 5-HTT gene in African Americans and Caucasians, and if confirmed, will provide an important tool for identifying at-risk individuals and estimating the risk of recurrence.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19014073"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12599191"
},
{
- "id": "pmid:19012814",
+ "id": "pmid:12438470",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/19012814",
- "title": "Obsessive and compulsive symptoms in prediagnosed Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/12438470",
+ "title": "Unilateral transplantation of human primary fetal tissue in four patients with Huntington's disease: NEST-UK safety report ISRCTN no 36485475.",
"type": "article-journal",
- "doi": "10.4088/jcp.v69n1111",
+ "doi": "10.1136/jnnp.73.6.678",
"authors": [
- ["Leigh J", "Beglinger"],
- ["Jane S", "Paulsen"],
- ["David B", "Watson"],
- ["Chiachi", "Wang"],
- ["Kevin", "Duff"],
- ["Douglas R", "Langbehn"],
- ["David J", "Moser"],
- ["Henry L", "Paulson"],
- ["Elizabeth H", "Aylward"],
- ["Noelle E", "Carlozzi"],
- ["Sarah", "Queller"],
- ["Julie C", "Stout"]
+ ["A E", "Rosser"],
+ ["R A", "Barker"],
+ ["T", "Harrower"],
+ ["C", "Watts"],
+ ["M", "Farrington"],
+ ["A K", "Ho"],
+ ["R M", "Burnstein"],
+ ["D K", "Menon"],
+ ["J H", "Gillard"],
+ ["J", "Pickard"],
+ ["S B", "Dunnett"]
],
- "publisher": "The Journal of clinical psychiatry",
- "issn": "1555-2101",
- "date": "2008-09-09",
- "abstract": "Obsessive and compulsive symptoms (OCS) are more prevalent in patients with diagnosed Huntington's disease (HD) than in the general population. Although psychiatric symptoms have been reported in individuals with the HD gene expansion prior to clinical diagnosis (pre-HD), little is known about OCS in this phase of disease.",
+ "publisher": "Journal of neurology, neurosurgery, and psychiatry",
+ "issn": "0022-3050",
+ "date": "2002-12-01",
+ "abstract": "Huntington's disease (HD) is an inherited autosomal dominant condition in which there is a CAG repeat expansion in the huntingtin gene of 36 or more. Patients display progressive motor, cognitive, and behavioural deterioration associated with progressive cell loss and atrophy in the striatum. Currently there are no disease modifying treatments and current symptomatic treatments are only partially effective in the early to moderate stages. Neural transplantation is effective in animal models of HD and offers a potential strategy for brain repair in patients. The authors report a safety study of unilateral transplantation of human fetal striatal tissue into the striatum of four patients with HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19012814"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12438470"
},
{
- "id": "pmid:18986359",
+ "id": "pmid:12405543",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/18986359",
- "title": "Association of serotonin transporter gene-linked polymorphic region and variable number of tandem repeat polymorphism of the serotonin transporter gene in lichen simplex chronicus patients with psychiatric status.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/12405543",
+ "title": "Neuropsychological manifestations of the genetic mutation for Huntington's disease in presymptomatic individuals.",
"type": "article-journal",
- "doi": "10.1111/j.1365-4632.2008.03821.x",
+ "doi": "10.1017/s1355617702870060",
"authors": [
- ["Necmettin", "Kirtak"],
- ["H Serhat", "Inaloz"],
- ["Cenk", "Ak\u00e7ali"],
- ["Emin", "Erdal"],
- ["Hasan", "Herken"],
- ["Mehmet", "Yildirim"],
- ["H Gulcin", "Erguven"]
+ ["Jason", "Brandt"],
+ ["Barnett", "Shpritz"],
+ ["Ann Marie", "Codori"],
+ ["Russell", "Margolis"],
+ ["Adam", "Rosenblatt"]
],
- "publisher": "International journal of dermatology",
- "issn": "1365-4632",
- "date": "2008-10-01",
- "abstract": "The serotonin (5-hydroxytryptamine; 5-HT) is a key neurotransmitter in the central nervous system and a responsible mediator for the itch. Dysregulation of serotonergic pathways has been implicated in the pathogenesis of many complex neuropsychiatric diseases.",
+ "publisher": "Journal of the International Neuropsychological Society : JINS",
+ "issn": "1355-6177",
+ "date": "2002-11-01",
+ "abstract": "A triplet repeat (CAG) expansion mutation in the huntingtin gene on chromosome 4 is responsible for Huntington's disease (HD). Presymptomatic genetic testing for this mutation has identified clinically normal persons who are virtually certain to develop this dementing illness if they live a normal lifespan. The present study sought to determine whether these \"mutation-positive\" persons have impairments in cognitive functioning. Seventy-five mutation-positive persons did not differ from 128 mutation-negative persons on tests selected for their sensitivity to early-stage HD. Interestingly, however, those with the mutation viewed themselves as more likely to develop HD than did those without the mutation. Among mutation-positive subjects, having a longer CAG repeat mutation was likewise not associated with cognitive impairment. However, being closer to estimated disease onset (a product of repeat length and parent's age at onset) was associated with selected cognitive impairments. When viewed in light of previous studies showing atrophy of the caudate nucleus and putamen in mutation-carriers who are close to onset but not those far from onset, these results suggest that subtle changes in brain and behavior may be detected shortly before subjects with the HD mutation develop sufficient signs and symptoms for diagnosis. Conceptual and methodological problems associated with the search for presymptomatic cognitive and behavioral indicators of dementing illness are discussed.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18986359"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12405543"
},
{
- "id": "pmid:18854207",
+ "id": "pmid:12393802",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/18854207",
- "title": "Progressive synaptic pathology of motor cortical neurons in a BAC transgenic mouse model of Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/12393802",
+ "title": "Aggregated polyglutamine peptides delivered to nuclei are toxic to mammalian cells.",
"type": "article-journal",
- "doi": "10.1016/j.neuroscience.2008.09.020",
+ "doi": "10.1093/hmg/11.23.2905",
"authors": [
- ["J", "Spampanato"],
- ["X", "Gu"],
- ["X W", "Yang"],
- ["I", "Mody"]
+ ["Wen", "Yang"],
+ ["John R", "Dunlap"],
+ ["Richard B", "Andrews"],
+ ["Ronald", "Wetzel"]
],
- "publisher": "Neuroscience",
- "issn": "0306-4522",
- "date": "2008-09-18",
- "abstract": "Huntington's disease (HD) is a neurodegenerative disorder caused by a polyglutamine repeat expansion in huntingtin. A newly developed bacterial artificial chromosome transgenic mouse model (BACHD) reproduces phenotypic features of HD including predominantly neuropil-associated protein aggregation and progressive motor dysfunction with selective neurodegenerative pathology. Motor dysfunction has been shown to precede neuropathology in BACHD mice. We therefore investigated the progression of synaptic pathology in pyramidal cells and interneurons of the superficial motor cortex of BACHD mice. Whole-cell patch clamp recordings were performed on layer 2/3 primary motor cortical pyramidal cells and parvalbumin interneurons from BACHD mice at 3 months, when the mice begin to demonstrate mild motor dysfunction, and at 6 months, when the motor dysfunction is more severe. Changes in synaptic variances were detectable at 3 months, and at 6 months BACHD mice display progressive synaptic pathology in the form of reduced cortical excitation and loss of inhibition onto pyramidal cells. These results suggest that progressive alterations of the superficial cortical circuitry may contribute to the decline of motor function in BACHD mice. The synaptic pathology occurs prior to neuronal degeneration and may therefore prove useful as a target for future therapeutic design.",
+ "publisher": "Human molecular genetics",
+ "issn": "0964-6906",
+ "date": "2002-11-01",
+ "abstract": "A number of observations point to the aggregation of expanded polyglutamine [poly(Q)]-containing proteins as playing a central role in the etiology of Huntington's disease (HD) and other expanded CAG-repeat diseases. Transfected cell and transgenic animal models provide some of this support, but irrefutable data on the cytotoxicity of poly(Q) aggregates is lacking. This may be due in part to difficulties in observing all aggregated states in these models, and in part to the inability to conclusively rule out the role of monomeric states of the poly(Q) protein. To address these questions, we produced aggregates of simple poly(Q) peptides in vitro and introduced them to mammalian cells in culture. We find that Cos-7 and PC-12 cells in culture readily take up aggregates of chemically synthesized poly(Q) peptides. Simple poly(Q) aggregates are localized to the cytoplasm and have little impact on cell viability. Aggregates of poly(Q) peptides containing a nuclear localization signal, however, are localized to nuclei and lead to dramatic cell death. Amyloid fibrils of a non-poly(Q) peptide are non-toxic, whether localized to the cytoplasm or nucleus. Nuclear localization of an aggregate of a short, Q(20), poly(Q) peptide is just as toxic as that of a long poly(Q) peptide, supporting the notion that the influence of poly(Q) repeat length on disease risk and age of onset is at the level of aggregation efficiency. The results support a direct role for poly(Q) aggregates in HD-related neurotoxicity.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18854207"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12393802"
},
{
- "id": "pmid:18844975",
+ "id": "pmid:12221159",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/18844975",
- "title": "Mutant huntingtin activates Nrf2-responsive genes and impairs dopamine synthesis in a PC12 model of Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/12221159",
+ "title": "Huntington's disease: a randomized, controlled trial using the NMDA-antagonist amantadine.",
"type": "article-journal",
- "doi": "10.1186/1471-2199-9-84",
+ "doi": "10.1212/wnl.59.5.694",
"authors": [
- ["Willeke M C", "van Roon-Mom"],
- ["Barry A", "Pepers"],
- ["Peter A C", "'t Hoen"],
- ["Carola A C M", "Verwijmeren"],
- ["Johan T", "den Dunnen"],
- ["Josephine C", "Dorsman"],
- ["Gertjan B", "van Ommen"]
+ ["L", "Verhagen Metman"],
+ ["M J", "Morris"],
+ ["C", "Farmer"],
+ ["M", "Gillespie"],
+ ["K", "Mosby"],
+ ["J", "Wuu"],
+ ["T N", "Chase"]
],
- "publisher": "BMC molecular biology",
- "issn": "1471-2199",
- "date": "2008-10-09",
- "abstract": "Huntington's disease is a progressive autosomal dominant neurodegenerative disorder that is caused by a CAG repeat expansion in the HD or Huntington's disease gene. Although micro array studies on patient and animal tissue provide valuable information, the primary effect of mutant huntingtin will inevitably be masked by secondary processes in advanced stages of the disease. Thus, cell models are instrumental to study early, direct effects of mutant huntingtin. mRNA changes were studied in an inducible PC12 model of Huntington's disease, before and after aggregates became visible, to identify groups of genes that could play a role in the early pathology of Huntington's disease.",
+ "publisher": "Neurology",
+ "issn": "0028-3878",
+ "date": "2002-09-10",
+ "abstract": "To examine the acute effects of the NMDA receptor antagonist amantadine on motor and cognitive function in Huntington's disease (HD).",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18844975"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12221159"
},
{
- "id": "pmid:18754766",
+ "id": "pmid:12218657",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/18754766",
- "title": "Altered frontostriatal coupling in pre-manifest Huntington's disease: effects of increasing cognitive load.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/12218657",
+ "title": "Major psychiatric disorders and the serotonin transporter gene (SLC6A4): family-based association studies.",
"type": "article-journal",
- "doi": "10.1111/j.1468-1331.2008.02253.x",
+ "doi": "10.1097/00041444-200209000-00004",
"authors": [
- ["R C", "Wolf"],
- ["F", "Sambataro"],
- ["N", "Vasic"],
- ["C", "Sch\u00f6nfeldt-Lecuona"],
- ["D", "Ecker"],
- ["B", "Landwehrmeyer"]
+ ["Albena", "Dimitrova"],
+ ["Lyudmila", "Georgieva"],
+ ["Ivan", "Nikolov"],
+ ["Nadejda", "Poriazova"],
+ ["Stefan", "Krastev"],
+ ["Draga", "Toncheva"],
+ ["Michael J", "Owen"],
+ ["George", "Kirov"]
],
- "publisher": "European journal of neurology",
- "issn": "1468-1331",
- "date": "2008-08-27",
- "abstract": "Functional neuroimaging studies have suggested a dysfunction of prefrontal regions in clinically pre-symptomatic individuals with the Huntington's disease (HD) gene mutation (pre-HD) during cognitive processing. The objective of this study was to test the impact of cognitive demand on prefrontal connectivity in pre-HD individuals.",
+ "publisher": "Psychiatric genetics",
+ "issn": "0955-8829",
+ "date": "2002-09-01",
+ "abstract": "The serotonin transporter (5-HTT) is a suitable candidate gene to test for involvement in the pathogenesis of major psychiatric disorders. We used the method of family-based controls to test for association between disease and a variable number tandem repeat (VNTR) in intron 2 of the gene, which has received support for involvement in the pathogenesis of several psychiatric disorders. We analysed 413 proband-parent trios of Bulgarian origin: 266 had a schizophrenic proband, 103 had a bipolar proband and 44 had a schizoaffective proband. The results were analysed using the extended transmission disequilibrium test. Possible effects of different alleles on certain clinical variables were examined by correlation analysis. Three alleles were detected: STin2.9, STin2.10 and STin2.12. None of the three diagnostic samples showed preferential transmission of alleles that reached conventional levels of statistical significance. We could not confirm previous results that STin2.12 allele increases susceptibility to bipolar disorder type I. The rare STin2.9 showed a non-significant trend for preferential transmission in the sample as a whole: 18 transmitted versus 11 non-transmitted (P = 0.2). The VNTR polymorphism in the 5-HTT gene does not appear to be a major risk factor for increasing susceptibility to major psychiatric disorders.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18754766"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12218657"
},
{
- "id": "pmid:18608348",
+ "id": "pmid:12208565",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/18608348",
- "title": "Insufficient ex vivo expansion of Valpha24(+) natural killer T cells in malignant lymphoma patients related to the suppressed expression of CD1d molecules on CD14(+) cells.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/12208565",
+ "title": "No association between the serotonergic polymorphisms and incidence of nausea induced by fluvoxamine treatment.",
"type": "article-journal",
- "doi": "10.1080/14653240802072747",
+ "doi": "10.1016/s0924-977x(02)00056-1",
"authors": [
- ["O", "Imataki"],
- ["Y", "Heike"],
- ["H", "Makiyama"],
- ["A", "Iizuka"],
- ["Y", "Ikarashi"],
- ["T", "Ishida"],
- ["H", "Wakasugi"],
- ["Y", "Takaue"]
+ ["Hitoshi", "Takahashi"],
+ ["Keizo", "Yoshida"],
+ ["Kenich", "Ito"],
+ ["Kazuhiro", "Sato"],
+ ["Mitsuhiro", "Kamata"],
+ ["Hisashi", "Higuchi"],
+ ["Tetsuo", "Shimizu"],
+ ["Kunihiko", "Ito"],
+ ["Kazuyuki", "Inoue"],
+ ["Takehiko", "Tezuka"],
+ ["Toshio", "Suzuki"],
+ ["Tadashi", "Ohkubo"],
+ ["Kazunobu", "Sugawara"]
],
- "publisher": "Cytotherapy",
- "issn": "1477-2566",
- "date": "2008-01-01",
- "abstract": "Valpha24(+) natural killer T (NKT) cell is a human counterpart of mice Valpha14(+) NKT cell that has a regulatory role for innate and acquired potential antitumor activity. The efficient expansion of NKT cells is an obstacle to the clinical application of Valpha24(+) NKT cells for immunotherapy.",
+ "publisher": "European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology",
+ "issn": "0924-977X",
+ "date": "2002-10-01",
+ "abstract": "We investigated the association between serotonergic polymorphisms and incidence of nausea, which is the most frequent side-effect of selective serotonin reuptake inhibiters (SSRIs), in 66 patients treated with fluvoxamine in a protocolized-dosing method. We focused on three polymorphisms of serotonin (5-HT) neuronal systems such as 5-HT transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR), a variable number of tandem repeat (VNTR) polymorphism in the second intron of the 5-HTT gene (STin2) and tryptophan hydroxylase (TPH) gene polymorphism in intron 7 (TPH-A218C), which have been reported to possess positive association with treatment response to SSRIs. In addition to this, the relationship between development of nausea and treatment response was also analyzed. Results suggested that these three polymorphisms did not affect the development of fluvoxamine-induced nausea, and that incidence of nausea was not a phenomenon that predicts the treatment response to fluvoxamine.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18608348"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12208565"
},
{
- "id": "pmid:18512767",
+ "id": "pmid:11978769",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/18512767",
- "title": "The relationship between CAG repeat length and clinical progression in Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11978769",
+ "title": "Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy.",
"type": "article-journal",
- "doi": "10.1002/mds.21988",
+ "doi": "10.1093/hmg/11.9.1107",
"authors": [
- ["Bernard", "Ravina"],
- ["Megan", "Romer"],
- ["Radu", "Constantinescu"],
- ["Kevin", "Biglan"],
- ["Alicia", "Brocht"],
- ["Karl", "Kieburtz"],
- ["Ira", "Shoulson"],
- ["Michael P", "McDermott"]
+ ["Brinda", "Ravikumar"],
+ ["Rainer", "Duden"],
+ ["David C", "Rubinsztein"]
],
- "publisher": "Movement disorders : official journal of the Movement Disorder Society",
- "issn": "1531-8257",
- "date": "2008-07-15",
- "abstract": "The objective of this study was to examine the relationship between CAG repeat length (CAGn) and clinical progression in patients with Huntington's disease (HD). There are conflicting reports about the relationship between CAGn and clinical progression of HD. We conducted an analysis of data from the Coenzyme Q10 and Remacemide Evaluation in Huntington's Disease (CARE-HD) clinical trial. We modeled progression over 30 months on the Unified Huntington's Disease Rating Scale (UHDRS) and supplemental neuropsychological and behavioral tests using multiple linear regression. Mean subject age was 47.9 +/- 10.5 years and mean CAGn was 45.0 +/- 4.1. Multiple linear regression revealed statistically significant associations between CAGn and worsening on several motor, cognitive, and functional outcomes, but not behavioral outcomes. Many effects were clinically important; 10 additional CAG repeats were associated with an 81% increase in progression on the Independence Scale. These associations were not observed in the absence of age adjustment. Age at the time of assessment confounds the association between CAGn and progression. Adjusting for age shows that longer CAGn is associated with greater clinical progression of HD. This finding may account for the variable results from previous studies examining CAGn and progression. Adjusting for CAGn may be important for clinical trials.",
+ "publisher": "Human molecular genetics",
+ "issn": "0964-6906",
+ "date": "2002-05-01",
+ "abstract": "Protein conformational disorders (PCDs), such as Alzheimer's disease, Huntington's disease (HD), Parkinson's disease and oculopharyngeal muscular dystrophy, are associated with proteins that misfold and aggregate. Here we have used exon 1 of the HD gene with expanded polyglutamine [poly(Q)] repeats and enhanced green fluorescent protein tagged to 19 alanines as models for aggregate-prone proteins, to investigate the pathways mediating their degradation. Autophagy is involved in the degradation of these model proteins, since they accumulated when cells were treated with different inhibitors acting at distinct stages of the autophagy-lysosome pathway, in two different cell lines. Furthermore, rapamycin, which stimulates autophagy, enhanced the clearance of our aggregate-prone proteins. Rapamycin also reduced the appearance of aggregates and the cell death associated with the poly(Q) and polyalanine [poly(A)] expansions. Since rapamycin is used clinically, this drug or related analogues may be suitable candidates for therapeutic investigation in HD and related diseases. We have also re-examined the role of the proteasome, since previous studies in poly(Q) diseases have used lactacystin as an inhibitor--recent studies have shown that lactacystin may also affect lysosomal function. Both lactacystin and the specific proteasomal inhibitor epoxomicin increased soluble protein levels of the poly(Q) constructs, suggesting that these are also cleared by the proteasome. However, while poly(Q) aggregation was enhanced by lactacystin in our inducible PC12 cell model, aggregation was reduced by epoxomicin, suggesting that some other protein(s) induced by epoxomicin may regulate poly(Q) aggregation.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18512767"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11978769"
},
{
- "id": "pmid:18502655",
+ "id": "pmid:11920857",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/18502655",
- "title": "Full length mutant huntingtin is required for altered Ca2+ signaling and apoptosis of striatal neurons in the YAC mouse model of Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11920857",
+ "title": "Correlation between serotonin uptake in human blood platelets with the 44-bp polymorphism and the 17-bp variable number of tandem repeat of the serotonin transporter.",
"type": "article-journal",
- "doi": "10.1016/j.nbd.2008.03.010",
+ "doi": "10.1002/ajmg.10119",
"authors": [
- ["Hua", "Zhang"],
- ["Qin", "Li"],
- ["Rona K", "Graham"],
- ["Elizabeth", "Slow"],
- ["Michael R", "Hayden"],
- ["Ilya", "Bezprozvanny"]
+ ["Rolf", "Kaiser"],
+ ["Bruno", "M\u00fcller-Oerlinghausen"],
+ ["Diana", "Filler"],
+ ["Pierre-Benoit", "Tremblay"],
+ ["Anne", "Bergh\u00f6fer"],
+ ["Ivar", "Roots"],
+ ["J\u00fcrgen", "Brockm\u00f6ller"]
],
- "publisher": "Neurobiology of disease",
- "issn": "1095-953X",
- "date": "2008-04-16",
- "abstract": "Huntington's disease (HD) is caused by a progressive loss of striatal medium spiny neurons (MSN). The molecular trigger of HD is a polyglutamine expansion in the Huntingtin protein (Htt). The mutant Htt protein forms insoluble nuclear aggregates which have been proposed to play a key role in causing neuronal cell death in HD. Other lines of investigation suggest that expression of mutant Htt facilitates activity of the NR2B subtype of NMDA receptors and the type 1 inositol 1,4,5-trisphosphate receptors (InsP(3)R1), and that disturbed calcium (Ca(2+)) signaling causes apoptosis of MSNs in HD. The YAC128 transgenic HD mouse model expresses the full-length human Htt protein with 120Q CAG repeat expansion and displays an age-dependent loss of striatal neurons as seen in human HD brain. In contrast, the shortstop mice express an amino-terminal fragment of the mutant Htt protein (exons 1 and 2) and display no behavioral abnormalities or striatal neurodegeneration despite widespread formation of neuronal inclusions. Here we compared Ca(2+) signals in primary MSN neuronal cultures derived from YAC128 and shortstop mice to their wild-type non-transgenic littermates. Repetitive application of glutamate results in supranormal Ca(2+) responses in YAC128 MSNs, but not in shortstop MSNs. In addition, while currents mediated by the NR2B subtype of NMDA receptors were increased in YAC128 MSNs, currents in SS MSNs were found to be similar to WT. Furthermore, YAC128 MSNs were sensitized to glutamate-induced apoptosis. Consistent with these findings, we found that application of glutamate induced rapid loss of mitochondrial membrane potential in YAC128 MSNs. In contrast, SS MSNs do not show increased cell death postglutamate treatment nor accelerated loss of mitochondrial membrane potential following glutamate stimulation. Glutamate-induced loss of mitochondrial membrane potential in YAC128 MSNs could be prevented by inhibitors of NR2B NMDA receptors and mGluR1/5 receptors. Our results are consistent with the hypothesis that disturbed neuronal Ca(2+) signaling plays a significant role in the degeneration of MSN containing full-length mutant Htt(exp). Furthermore, the results obtained with neurons from shortstop mice provide additional evidence that not all fragments of mutant Htt(exp) are toxic to neurons.",
+ "publisher": "American journal of medical genetics",
+ "issn": "0148-7299",
+ "date": "2002-04-08",
+ "abstract": "Dysfunctions of the central serotonin (5-hydroxytryptamine, 5-HT) system seem to be associated with psychiatric disorders such as schizophrenia or depression. Previous studies suggested that a 44-bp insertion/deletion polymorphism of the 5-HT transporter (5-HTT) promoter region might influence the transcriptional activity of the 5-HTT gene, and the insertion variant resulted in increased 5-HTT expression and 5-HT uptake. Moreover, a 17-bp variable number of tandem repeat (VNTR) polymorphism of the second intron may act as a transcriptional regulator with allele dependent differential enhancer-like properties. Since the 5-HTT of human platelets shares many properties with the transporter of neural tissue, platelets are widely used as a surrogate tissue source, possibly reflecting central 5-HT metabolism. Therefore, we investigated the impact of the 44-bp polymorphism and the 17-bp VNTR for 5-HT uptake in platelets of 50 male subjects. We found no significant effect of the 44-bp polymorphism and of the 17-bp VNTR on maximum rate (Vmax) of 5-HT uptake. However, individuals homozygous for the 5-HTT intron 2 allele with 12 repeats (STin2.12) of the 17-bp VNTR appeared to have lower affinity of 5-HT uptake than individuals heterozygous for the STin2.10/STin2.9 allele. This was also observed for the combined analysis of both polymorphisms. In conclusion, we found no association between the different genotypes of the 44-bp polymorphism and the 17-bp VNTR and maximum rate of 5-HT uptake into platelets.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18502655"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11920857"
},
{
- "id": "pmid:18413470",
+ "id": "pmid:11741397",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/18413470",
- "title": "Rapid eye movement sleep disturbances in Huntington disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11741397",
+ "title": "Inhibition of polyglutamine aggregation in R6/2 HD brain slices-complex dose-response profiles.",
"type": "article-journal",
- "doi": "10.1001/archneur.65.4.482",
+ "doi": "10.1006/nbdi.2001.0438",
"authors": [
- ["Isabelle", "Arnulf"],
- ["J\u00f8rgen", "Nielsen"],
- ["Ebba", "Lohmann"],
- ["Johannes", "Schiefer"],
- ["Edward", "Wild"],
- ["Poul", "Jennum"],
- ["Eric", "Konofal"],
- ["Matthew", "Walker"],
- ["Delphine", "Oudiette"],
- ["Sarah", "Tabrizi"],
- ["Alexandra", "Durr"]
+ ["D L", "Smith"],
+ ["R", "Portier"],
+ ["B", "Woodman"],
+ ["E", "Hockly"],
+ ["A", "Mahal"],
+ ["W E", "Klunk"],
+ ["X J", "Li"],
+ ["E", "Wanker"],
+ ["K D", "Murray"],
+ ["G P", "Bates"]
],
- "publisher": "Archives of neurology",
- "issn": "1538-3687",
- "date": "2008-04-01",
- "abstract": "Sleep disorders including insomnia, movements during sleep, and daytime sleepiness are common but poorly studied in Huntington disease (HD).",
+ "publisher": "Neurobiology of disease",
+ "issn": "0969-9961",
+ "date": "2001-12-01",
+ "abstract": "Huntington's disease (HD) is a late onset neurodegenerative disorder caused by a CAG/polyglutamine (polyQ) repeat expansion. PolyQ aggregates can be detected in the nuclei and processes of neurons in HD patients and mouse models prior to the onset of symptoms. The misfolding and aggregation pathway is an important therapeutic target. To better test the efficacy of aggregation inhibitors, we have developed an organotypic slice culture system. We show here that the formation of polyQ aggregates in hippocampal slices established from the R6/2 mouse follows the same prescribed sequence as occurs in vivo. Using this assay, we show that Congo red and chrysamine G can modulate aggregate formation, but show complex dose-response curves. Oral administration of creatine has been shown to delay the onset of all aspects of the phenotype and neuropathology in R6/2 mice. We show here that creatine can similarly inhibit aggregate formation in the slice culture assay.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18413470"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11741397"
},
{
- "id": "pmid:18403212",
+ "id": "pmid:11704263",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/18403212",
- "title": "Sertraline slows disease progression and increases neurogenesis in N171-82Q mouse model of Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11704263",
+ "title": "Evaluation of R6/2 HD transgenic mice for therapeutic studies in Huntington's disease: behavioral testing and impact of diabetes mellitus.",
"type": "article-journal",
- "doi": "10.1016/j.nbd.2008.01.015",
+ "doi": "10.1016/s0166-4328(01)00261-3",
"authors": [
- ["Wenzhen", "Duan"],
- ["Qi", "Peng"],
- ["Naoki", "Masuda"],
- ["Eric", "Ford"],
- ["Erik", "Tryggestad"],
- ["Bruce", "Ladenheim"],
- ["Ming", "Zhao"],
- ["Jean Lud", "Cadet"],
- ["John", "Wong"],
- ["Christopher A", "Ross"]
+ ["H G", "L\u00fcesse"],
+ ["J", "Schiefer"],
+ ["A", "Spruenken"],
+ ["C", "Puls"],
+ ["F", "Block"],
+ ["C M", "Kosinski"]
],
- "publisher": "Neurobiology of disease",
- "issn": "1095-953X",
- "date": "2008-03-10",
- "abstract": "Huntington's disease (HD) is an inherited progressive neurodegenerative disorder resulting from CAG repeat expansion in the gene that encodes for the protein huntingtin. To identify neuroprotective compound (s) that can slow down disease progression and can be administered long term with few side effects in Huntington's disease, we investigated the effect of sertraline, a selective serotonin reuptake inhibitor (SSRI) which has been shown to upregulate BDNF levels in rodent brains. We report here that in HD mice sertraline increased BDNF levels, preserved chaperone protein HSP70 and Bcl-2 levels in brains, attenuated the progression of brain atrophy and behavioral abnormalities and thereby increased survival. Sertraline also enhanced neurogenesis, which appeared to be responsible for mediating the beneficial effects of sertraline in HD mice. Additionally, the effective levels of sertraline are comparable to the safe levels achievable in humans. The findings suggest that sertraline is a potential candidate for treatment of HD patients.",
+ "publisher": "Behavioural brain research",
+ "issn": "0166-4328",
+ "date": "2001-11-29",
+ "abstract": "R6/2 transgenic mice express exon 1 of the human Huntington's disease (HD) gene with an increased CAG repeat length. They develop a progressive neurological phenotype, die within 12-14 weeks of age and were also found to develop diabetes mellitus. Since R6/2 mice are broadly used to screen for potential therapies in HD, the aim of this study was (a) to search for behavioral tests that are best applicable to monitor the behavioral abnormalities in therapy studies and (b) to investigate the extent to which diabetes influences the disease phenotype. We found that the rotarod test for motor coordination and the open field test for spontaneous explorative behavior were useful to monitor the progressive behavioral deterioration of R6/2 mice. An accelerating rotarod paradigm was superior over testing with a rotarod at various fixed speeds since it leads to similar results with less repetitive daily trials so that exhaustion cannot contribute substantially to their decline in performance. With the Morris water maze, however, it was only possible to monitor cognitive decline in visuo-spatial learning in the first weeks of disease since, at later stages, mice were not able to learn the task adequately. A latent diabetes mellitus was found in all transgenic mice demonstrated by a pathological glucose tolerance. Only 26% of the mice, however, were found to develop a manifest diabetes with increasing blood glucose levels on normal diet over the disease period. R6/2 mice with manifest and latent diabetes showed no significant differences in survival, weight loss, motor coordination, or spontaneous explorative behavior. These results suggest that diabetes mellitus is not a major contributing factor to the disease phenotype.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18403212"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11704263"
},
{
- "id": "pmid:18403126",
+ "id": "pmid:11689489",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/18403126",
- "title": "Dopamine D1 receptor-mediated aggregation of N-terminal fragments of mutant huntingtin and cell death in a neuroblastoma cell line.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11689489",
+ "title": "Centrosome disorganization in fibroblast cultures derived from R6/2 Huntington's disease (HD) transgenic mice and HD patients.",
"type": "article-journal",
- "doi": "10.1016/j.neuroscience.2008.02.052",
+ "doi": "10.1093/hmg/10.21.2425",
"authors": [
- ["P", "Robinson"],
- ["M", "Lebel"],
- ["M", "Cyr"]
+ ["K", "Sathasivam"],
+ ["B", "Woodman"],
+ ["A", "Mahal"],
+ ["F", "Bertaux"],
+ ["E E", "Wanker"],
+ ["D T", "Shima"],
+ ["G P", "Bates"]
],
- "publisher": "Neuroscience",
- "issn": "1873-7544",
- "date": "2008-03-06",
- "abstract": "Huntington's disease (HD) is an inherited neurodegenerative disorder caused by abnormal CAG repeat expansion in the IT15 gene encoding huntingtin protein (htt). Mutated htt is predicted to acquire toxic properties in specific brain regions. For instance, striatal neurons expressing dopamine receptors predominantly degenerate in HD patients. Although the basis of this specific vulnerability remains unclear, a great deal of evidence has documented the ability of the dopamine system to modulate the toxicity of expanded htt. To investigate the relationship between dopamine receptors and expanded htt, we transfected enhanced green fluorescent proteins (EGFP) tagged to normal (25 CAG) or mutant (103 CAG) htt in SK-N-MC neuroblastoma cells that endogenously express D1 receptors. Forming nuclear and cytoplasmic aggregates, mutant htt-EGFP was toxic to cells beyond 24 h post-transfection. Remarkably, low doses of a selective D1 receptors agonist or forskolin, an activator of adenylate cyclase, accelerated the formation of mutant htt nuclear aggregates, whereas the number of cytoplasmic aggregates was decreased. These effects were associated with a minor increase in cell death. Understanding the functional bases of these effects may further elucidate the role of dopamine receptors signaling in the complex pathophysiology of HD.",
+ "publisher": "Human molecular genetics",
+ "issn": "0964-6906",
+ "date": "2001-10-01",
+ "abstract": "Huntington's disease (HD) is a progressive neurological disorder caused by a CAG/polyglutamine repeat expansion. We have previously generated the R6/2 mouse model that expresses exon 1 of the human HD gene containing CAG repeats in excess of 150. These mice develop a progressive neurological phenotype with a rapid onset and progression. We show here that it is impossible to establish fibroblast lines from these mice at 12 weeks of age, whilst this can be achieved without difficulty at 6 and 9 weeks. Cultures derived from mice at 12 weeks contained a high frequency of dysmorphic cells, including cells with an aberrant nuclear morphology and a high frequency of micronuclei and large vacuoles. All of these features were also present in a line derived from a juvenile HD patient. Fibroblast lines derived from R6/2 mice and from HD patients were found to have a high frequency of multiple centrosomes which could account for all of the observed phenotypes including a reduced mitotic index, high frequency of aneuploidy and persistence of the midbody. We were unable to detect large insoluble polyglutamine aggregates in either the mouse or human lines. We have identified a novel progressive HD pathology that occurs in cells of non-central nervous system origin. An investigation of the pathological consequences of the HD mutation in these cells will provide insight into cellular basis of the disease.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18403126"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11689489"
},
{
- "id": "pmid:18349696",
+ "id": "pmid:11558794",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/18349696",
- "title": "Low level of harm avoidance is associated with serotonin transporter functional haplotype in alcohol-dependent individuals.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11558794",
+ "title": "A disorder similar to Huntington's disease is associated with a novel CAG repeat expansion.",
"type": "article-journal",
- "doi": "10.1097/ypg.0b013e3282f60333",
+ "doi": "",
"authors": [
- ["Gabi", "Koller"],
- ["Peter", "Zill"],
- ["Thomas", "Skoruppa"],
- ["Brigitta", "Bondy"],
- ["Ulrich W", "Preuss"],
- ["Michael", "Soyka"]
+ ["R L", "Margolis"],
+ ["E", "O'Hearn"],
+ ["A", "Rosenblatt"],
+ ["V", "Willour"],
+ ["S E", "Holmes"],
+ ["M L", "Franz"],
+ ["C", "Callahan"],
+ ["H S", "Hwang"],
+ ["J C", "Troncoso"],
+ ["C A", "Ross"]
],
- "publisher": "Psychiatric genetics",
- "issn": "1473-5873",
- "date": "2008-04-01",
- "abstract": "The serotonin transporter gene (SLC6A4) encodes a trans-membrane protein (5-HTT) that plays an important role in regulating serotonergic neurotransmission, which is known to be involved in many psychiatric disorders. A polymorphism in the transcriptional control region containing long (L) and short (S) variants (5-HTTLPR) as well as alleles of the variable number tandem repeats (VNTR) region were demonstrated. Higher serotonin levels among carriers of the S allele might exhibit increased liability of serotonin-mediated, psychopathology-like anxiety and depression and may impair social skills reflected by harm avoidance.",
+ "publisher": "Annals of neurology",
+ "issn": "0364-5134",
+ "date": "2001-09-01",
+ "abstract": "Huntington's disease (HD) is an autosomal dominant disorder characterized by abnormalities of movement, cognition, and emotion and selective atrophy of the striatum and cerebral cortex. While the etiology of HD is known to be a CAG trinucleotide repeat expansion, the pathways by which this mutation causes HD pathology remain unclear. We now report a large pedigree with an autosomal dominant disorder that is clinically similar to HD and that arises from a different CAG expansion mutation. The disorder is characterized by onset in the fourth decade, involuntary movements and abnormalities of voluntary movement, psychiatric symptoms, weight loss, dementia, and a relentless course with death about 20 years after disease onset. Brain magnetic resonance imaging scans and an autopsy revealed marked striatal atrophy and moderate cortical atrophy, with striatal neurodegeneration in a dorsal to ventral gradient and occasional intranuclear inclusions. All tested affected individuals, and no tested unaffecteds, have a CAG trinucleotide repeat expansion of 50 to 60 triplets, as determined by the repeat expansion detection assay. Tests for the HD expansion, for all other known CAG expansion mutations, and for linkage to chromosomes 20p and 4p were negative, indicating that this mutation is novel. Cloning the causative CAG expansion mutation for this new disease, which we have termed Huntington's disease-like 2, may yield valuable insight into the pathogenesis of HD and related disorders.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18349696"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11558794"
},
{
- "id": "pmid:18314311",
+ "id": "pmid:11532992",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/18314311",
- "title": "Serotonin transporter gene polymorphisms: effect on serotonin transporter availability in the brain of suicide attempters.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11532992",
+ "title": "Polyglutamine expansions cause decreased CRE-mediated transcription and early gene expression changes prior to cell death in an inducible cell model of Huntington's disease.",
"type": "article-journal",
- "doi": "10.1016/j.pscychresns.2007.07.004",
+ "doi": "10.1093/hmg/10.17.1829",
"authors": [
- ["Jessica", "Bah"],
- ["Mats", "Lindstr\u00f6m"],
- ["Lars", "Westberg"],
- ["Louise", "Manner\u00e5s"],
- ["Erik", "Ryding"],
- ["Susanne", "Henningsson"],
- ["Jonas", "Melke"],
- ["Ingmar", "Ros\u00e9n"],
- ["Lil", "Tr\u00e4skman-Bendz"],
- ["Elias", "Eriksson"]
+ ["A", "Wyttenbach"],
+ ["J", "Swartz"],
+ ["H", "Kita"],
+ ["T", "Thykjaer"],
+ ["J", "Carmichael"],
+ ["J", "Bradley"],
+ ["R", "Brown"],
+ ["M", "Maxwell"],
+ ["A", "Schapira"],
+ ["T F", "Orntoft"],
+ ["K", "Kato"],
+ ["D C", "Rubinsztein"]
],
- "publisher": "Psychiatry research",
- "issn": "0165-1781",
- "date": "2008-04-15",
- "abstract": "The efficacy of serotonin reuptake inhibitors in depression and anxiety disorders suggests the gene coding for the serotonin transporter (5-HTT), SLC6A4, as a candidate of importance for these conditions. Positive findings regarding associations between polymorphisms in SLC6A4 have been reported, indicating that these polymorphisms may influence anxiety-related personality traits, as well as the risk of developing depression and suicidality. Serotonin 5-HTT availability was assessed with single photon emission computed tomography (SPECT), using (123)I-beta-CIT as ligand, in a population of unmedicated male suicide attempters (n=9) and in matched controls (n=9). Two polymorphisms in SLC6A4 were assessed, including the 5-HTTLPR located in the promoter region and a variable number of tandem repeats (VNTR) polymorphism in intron 2 (STin2). In suicide attempters, but not in controls, low 5-HTT availability was associated with the S allele of 5-HTTLPR and with the 12 repeat allele of STin2. Data suggest that polymorphisms in SLC6A4 may influence the expression of the brain serotonin transporter in suicide attempters.",
+ "publisher": "Human molecular genetics",
+ "issn": "0964-6906",
+ "date": "2001-08-15",
+ "abstract": "Huntington's disease (HD) is one of 10 known diseases caused by a (CAG)(n) trinucleotide repeat expansion that is translated into an abnormally long polyglutamine tract. We have developed stable inducible neuronal (PC12) cell lines that express huntingtin exon 1 with varying CAG repeat lengths under doxycycline (dox) control. The expression of expanded repeats is associated with aggregate formation, caspase-dependent cell death and decreased neurite outgrowth. Post-mitotic cells expressing mutant alleles were more prone to cell death compared with identical cycling cells. To determine early metabolic changes induced by this mutation in cell models, we studied changes in gene expression after 18 h dox induction, using Affymetrix arrays, cDNA filters and adapter-tagged competitive PCR (ATAC-PCR). At this time point there were low rates of inclusion formation, no evidence of mitochondrial compromise and no excess cell death in the lines expressing expanded compared with wild-type repeats. The expression profiles suggest novel targets for the HD mutation and were compatible with impaired cAMP response element (CRE)-mediated transcription, which we confirmed using CRE-luciferase reporter assays. Reduced CRE-mediated transcription may contribute to the loss of neurite outgrowth and cell death in polyglutamine diseases, as these phenotypes were partially rescued by treating cells with cAMP or forskolin.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18314311"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11532992"
},
{
- "id": "pmid:18307262",
+ "id": "pmid:11386982",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/18307262",
- "title": "Huntington's disease as caused by 34 CAG repeats.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11386982",
+ "title": "The role of serotonin transporter protein gene in antidepressant-induced mania in bipolar disorder: preliminary findings.",
"type": "article-journal",
- "doi": "10.1002/mds.21958",
+ "doi": "10.1001/archpsyc.58.6.539",
"authors": [
- ["J\u00fcrgen", "Andrich"],
- ["Larissa", "Arning"],
- ["Stefan", "Wieczorek"],
- ["Peter H", "Kraus"],
- ["Ralf", "Gold"],
- ["Carsten", "Saft"]
+ ["E", "Mundo"],
+ ["M", "Walker"],
+ ["T", "Cate"],
+ ["F", "Macciardi"],
+ ["J L", "Kennedy"]
],
- "publisher": "Movement disorders : official journal of the Movement Disorder Society",
- "issn": "1531-8257",
- "date": "2008-04-30",
- "abstract": "Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by an abnormal expansion of a polymorphic stretch of CAG repeats in the coding 5' part of the HD gene on chromosome 4p. Expansions of CAG blocks beyond 35 repeats are associated with the clinical presentation of HD. There is an intermediate range of rare alleles between 27 and 35 CAG repeats with a higher risk for further expansion in subsequent generations. Here, we report a 75-year-old male with clinical features of HD and 34 CAG repeat units.",
+ "publisher": "Archives of general psychiatry",
+ "issn": "0003-990X",
+ "date": "2001-06-01",
+ "abstract": "The occurrence of mania during antidepressant treatment is a key issue in the clinical management of bipolar disorder (BP). The serotonin transporter (5-HTT) is the selective site of action of most proserotonergic compounds used to treat bipolar depression. The 5-HTT gene (SLC6A4) has 2 known polymorphisms. The aim of this study was to investigate the role of the SLC6A4 variants in the pathogenesis of antidepressant-induced mania in BP.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18307262"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11386982"
},
{
- "id": "pmid:18204817",
+ "id": "pmid:11409734",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/18204817",
- "title": "Interspecies and intraspecies variations in the serotonin transporter gene intron 3 VNTR in nonhuman primates.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11409734",
+ "title": "UVB irradiation-induced apoptosis increased in lymphocytes of Huntington's disease patients.",
"type": "article-journal",
- "doi": "10.1007/s10329-007-0077-7",
+ "doi": "10.1097/00001756-200106130-00028",
"authors": [
- ["Miho", "Inoue-Murayama"],
- ["Emi", "Hibino"],
- ["Hiromi", "Iwatsuki"],
- ["Eiji", "Inoue"],
- ["Kyung-Won", "Hong"],
- ["Toshisada", "Nishida"],
- ["Ikuo", "Hayasaka"],
- ["Shin'ichi", "Ito"],
- ["Yuichi", "Murayama"]
+ ["K", "Jakab"],
+ ["Z", "Nov\u00e1k"],
+ ["J I", "Engelhardt"],
+ ["L", "Kem\u00e9ny"],
+ ["J", "K\u00e1lm\u00e1n"],
+ ["L", "V\u00e9csei"],
+ ["I", "Rask\u00f3"]
],
- "publisher": "Primates; journal of primatology",
- "issn": "0032-8332",
- "date": "2008-01-18",
- "abstract": "A variable number of tandem repeat (VNTR) polymorphism based on a 16 or 17-bp unit has been reported in the third intron of the human serotonin transporter gene (5-HTT). VNTRs have been shown to affect the transcriptional activity of genes, and VNTR polymorphisms possibly influence human personality and several psychoneurological disorders. To estimate the changes that occurred in the VNTRs during primate evolution, we amplified and sequenced the regions that corresponded to the human VNTRs in various primate species, including apes, Old World monkeys, and New World monkeys. The VNTR sequences were polymorphic in all the ape species examined, and alleles with repeat numbers of 18, 19, 23, and 24 in chimpanzees, 33, 35, 36, 38, and 40 in gorillas, 4 and 6 in orangutans, and 11, 13, 14, and 15 in gibbons were found. On the other hand, only a 5-repeat allele was detected in Old World monkeys such as the Japanese macaque and patas monkey. In this study we demonstrated for the first time that a repeat structure was not present in the corresponding regions in the New World monkeys examined, and only one unit sequence was found in them. These results suggested that the duplication of a unit in the VNTR region occurred in the Cercopithecidae species following the divergence of the Old World and New World monkeys, and various long repeated alleles were generated in humans and apes, except orangutans.",
+ "publisher": "Neuroreport",
+ "issn": "0959-4965",
+ "date": "2001-06-13",
+ "abstract": "Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG repeat expansion in the IT-15 gene coding for huntingtin. The mechanism of neuronal degeneration induced by the mutant huntingtin is not known. Apoptosis may play a role in it. Huntingtin is widely expressed in the cells, so abnormalities can be expected also in non-neural tissue. We examined the susceptibility of lymphocytes from HD patients, asymptomatic carriers and normal individuals to UVB irradiation-induced apoptosis. Lymphocytes from eight HD patients and two asymptomatic carriers showed increased apoptotic cell death compared to controls. Our results suggests that sensitivity of HD cells to induced apoptosis is not restricted to neurons.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18204817"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11409734"
},
{
- "id": "pmid:18192679",
+ "id": "pmid:11406606",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/18192679",
- "title": "Huntingtin-associated protein-1 is a modifier of the age-at-onset of Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11406606",
+ "title": "Expanded CAG repeats in exon 1 of the Huntington's disease gene stimulate dopamine-mediated striatal neuron autophagy and degeneration.",
"type": "article-journal",
- "doi": "10.1093/hmg/ddn003",
+ "doi": "10.1093/hmg/10.12.1243",
"authors": [
- ["Silke", "Metzger"],
- ["Juan", "Rong"],
- ["Huu-Phuc", "Nguyen"],
- ["Austin", "Cape"],
- ["Juergen", "Tomiuk"],
- ["Anne S", "Soehn"],
- ["Peter", "Propping"],
- ["Yun", "Freudenberg-Hua"],
- ["Jan", "Freudenberg"],
- ["Liang", "Tong"],
- ["Shi-Hua", "Li"],
- ["Xiao-Jiang", "Li"],
- ["Olaf", "Riess"]
+ ["", "Peters\u00e9n A"],
+ ["K E", "Larsen"],
+ ["G G", "Behr"],
+ ["N", "Romero"],
+ ["S", "Przedborski"],
+ ["P", "Brundin"],
+ ["D", "Sulzer"]
],
"publisher": "Human molecular genetics",
- "issn": "1460-2083",
- "date": "2008-01-11",
- "abstract": "A polyglutamine repeat expansion of more than 36 units in a protein called huntingtin (htt) is the only known cause of Huntington's disease (HD). The expanded repeat length is inversely correlated with the age-at-onset (AAO), however, the onset age among HD patients with CAG repeats below 60 units varies considerably. In addition to environmental factors, genetic factors different from the expanded CAG repeat length can modify the AAO of HD. We hypothezised that htt interacting proteins might contribute to this variation in the AAO and investigated human htt-associated protein-1 (HAP1) using genetic and functional assays. We identified six polymorphisms in the HAP1 gene including one that substitutes methionine (M441) for threonine (T441) at amino acid 441. Analyzing 980 European HD patients, we found that patients homozygous for the M441 genotype show an 8-year delay in the AAO. Functional assays demonstrated that human M441-HAP1 interacts with mutant htt more tightly than does human T441-HAP1, reduces soluble htt degraded products and protects against htt-mediated toxicity. We thus provide genetic and functional evidence that the M441-HAP1 polymorphism modifies the AAO of HD.",
+ "issn": "0964-6906",
+ "date": "2001-06-01",
+ "abstract": "Huntington's disease (HD) is caused by an expanded CAG repeat in exon 1 of the gene coding for the huntingtin protein. The cellular pathway by which this mutation induces HD remains unknown, although alterations in protein degradation are involved. To study intrinsic cellular mechanisms linked to the mutation, we examined dissociated postnatally derived cultures of striatal neurons from transgenic mice expressing exon 1 of the human HD gene carrying a CAG repeat expansion. While there was no difference in cell death between wild-type and mutant littermate-derived cultures, the mutant striatal neurons exhibited elevated cell death following a single exposure to a neurotoxic concentration of dopamine. The mutant neurons exposed to dopamine also exhibited lysosome-associated responses including induction of autophagic granules and electron-dense lysosomes. The autophagic/lysosomal compartments co-localized with high levels of oxygen radicals in living neurons, and ubiquitin. The results suggest that the combination of mutant huntingtin and a source of oxyradical stress (provided in this case by dopamine) induces autophagy and may underlie the selective cell death characteristic of HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18192679"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11406606"
},
{
- "id": "pmid:19378429",
+ "id": "pmid:11279522",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/19378429",
- "title": "Use of capillary electrophoresis for accurate determination of CAG repeats causing Huntington disease. An oligonucleotide design avoiding shadow bands.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11279522",
+ "title": "Trinucleotide expansion in haploid germ cells by gap repair.",
"type": "article-journal",
- "doi": "10.1080/00365510801915171",
+ "doi": "10.1038/86906",
"authors": [
- ["Sonia", "Blanco"],
- ["Antonio", "Suarez"],
- ["Sandra", "Gandia-Pla"],
- ["Carolina", "G\u00f3mez-Llorente"],
- ["Adelaida", "Ant\u00fanez"],
- ["Jose Antonio", "G\u00f3mez-Capilla"],
- ["M Esther", "F\u00e1rez-Vidal"]
+ ["I V", "Kovtun"],
+ ["C T", "McMurray"]
],
- "publisher": "Scandinavian journal of clinical and laboratory investigation",
- "issn": "0036-5513",
- "date": "2008-01-01",
- "abstract": "Huntington disease (HD) is a neurodegenerative disorder associated with the expansion of a polymorphic trinucleotide CAG repeat in the HD gene. We have developed an assay to accurately determine CAG repeats that combines a novel oligonucleotide design and the resolution of capillary electrophoresis. A mismatch in the second nucleotide from the 3' end enhanced specificity by avoiding mispriming and diminishing shadow bands and artifactual PCR products. The coupling of capillary electrophoresis analysis with the assay added the advantages of accuracy, high resolution, semi-automation, rapid analysis and low sample consumption. Analysis of 200 chromosomes in the Spanish population sample studied (control group) gave a peak frequency for 16 CAG repeats and of 7 triplets for CCG repeats. Diagnosis of HD was confirmed in 22 of 34 individuals with a range of CAG repeats from 39 to 52. Predictive testing was also carried out for 19 relatives of the HD families diagnosed at our laboratory. The method proposed in this article provides an accurate sizing of DNA repeats that can be applied to the analysis of DNA size-related disorders.",
+ "publisher": "Nature genetics",
+ "issn": "1061-4036",
+ "date": "2001-04-01",
+ "abstract": "Huntington disease (HD) is one of eight progressive neurodegenerative disorders in which the underlying mutation is a CAG expansion encoding a polyglutamine tract. The mechanism of trinucleotide expansion is poorly understood. Expansion is mediated by misaligned pairing of repeats and the inappropriate formation of DNA secondary structure as the duplex unpairs. It has never been clear, however, whether duplex unpairing occurs during mitotic replication or during strand-break repair. In simple organisms, trinucleotide expansion arises by replication slippage on either the leading or the lagging strand, homologous recombination, gene conversion, double-strand break repair and base excision repair; it is not clear which of these mechanisms is used in mammalian cells in vivo. We have followed heritable changes in CAG length in male transgenic mice. In germ cells, expansion is limited to the post-meiotic, haploid cell and therefore cannot involve mitotic replication or recombination between a homologous chromosome or a sister chromatid. Our data support a model in which expansion in the germ cells arises by gap repair and depends on a complex containing Msh2. Expansion occurs during gap-filling synthesis when DNA loops comprising the CAG trinucleotide repeats are sealed into the DNA strand.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19378429"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11279522"
},
{
- "id": "pmid:18091069",
+ "id": "pmid:11260214",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/18091069",
- "title": "Are cognitive changes progressive in prediagnostic HD?",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11260214",
+ "title": "The \"flap\" endonuclease gene FEN1 is excluded as a candidate gene implicated in the CAG repeat expansion underlying Huntington disease.",
"type": "article-journal",
- "doi": "10.1097/wnn.0b013e31815cfef8",
+ "doi": "10.1034/j.1399-0004.2001.590210.x",
"authors": [
- ["Julie C", "Stout"],
- ["Marjorie", "Weaver"],
- ["Andrea C", "Solomon"],
- ["Sarah", "Queller"],
- ["Siu", "Hui"],
- ["Shannon A", "Johnson"],
- ["Jacqueline", "Gray"],
- ["Xabier", "Beristain"],
- ["Joanne", "Wojcieszek"],
- ["Tatiana", "Foroud"]
+ ["C J", "Otto"],
+ ["E", "Almqvist"],
+ ["M R", "Hayden"],
+ ["S E", "Andrew"]
],
- "publisher": "Cognitive and behavioral neurology : official journal of the Society for Behavioral and Cognitive Neurology",
- "issn": "1543-3641",
- "date": "2007-12-01",
- "abstract": "To characterize neurocognitive signs of disease progression in prediagnosis and early Huntington disease (HD) and compare the sensitivity of 2 disease staging classification schemes for detecting these signs.",
+ "publisher": "Clinical genetics",
+ "issn": "0009-9163",
+ "date": "2001-02-01",
+ "abstract": "At least 12 disorders including Huntington disease (HD) are associated with expansion of a trinucleotide repeat (TNR). Factors contributing to the risk of expansion of TNRs and the mechanism of expansion have not been elucidated. Data from Saccharomyces cerevisiae suggest that the flap endonuclease FEN1 plays a role in expansion of repetitive DNA tracts. It has been hypothesized that insufficiency of FEN1 or a mutant FEN1 might contribute to the occurrence of expansion events of long repetitive DNA tracts after polymerase slippage events during lagging strand synthesis. The expression pattern of FEN1 was determined, and ubiquitous tissue expression, including germ cells, suggested that FEN1 has the potential to be involved in HD. Fifteen HD parent/child pairs that demonstrated intergenerational increases in CAG length of greater than 10 repeats were examined for possible mutations or polymorphisms within the FEN1 gene that could underlie the saltatory repeat expansions seen in these individuals. No alterations were observed compared to 50 controls, excluding FEN1 as a trans-acting factor underlying TNR expansion. The identification of a candidate gene(s) in HD or other CAG-expansion disorders implicated in TNR instability will elucidate the mechanism of expansion for this growing family of neurological disorders.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18091069"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11260214"
},
{
- "id": "pmid:18077673",
+ "id": "pmid:11106399",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/18077673",
- "title": "Mitochondrial sensitivity and altered calcium handling underlie enhanced NMDA-induced apoptosis in YAC128 model of Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11106399",
+ "title": "Transplanted fetal striatum in Huntington's disease: phenotypic development and lack of pathology.",
"type": "article-journal",
- "doi": "10.1523/jneurosci.3455-07.2007",
+ "doi": "10.1073/pnas.97.25.13877",
"authors": [
- ["Herman B", "Fernandes"],
- ["Kenneth G", "Baimbridge"],
- ["John", "Church"],
- ["Michael R", "Hayden"],
- ["Lynn A", "Raymond"]
+ ["T B", "Freeman"],
+ ["F", "Cicchetti"],
+ ["R A", "Hauser"],
+ ["T W", "Deacon"],
+ ["X J", "Li"],
+ ["S M", "Hersch"],
+ ["G M", "Nauert"],
+ ["P R", "Sanberg"],
+ ["J H", "Kordower"],
+ ["S", "Saporta"],
+ ["O", "Isacson"]
],
- "publisher": "The Journal of neuroscience : the official journal of the Society for Neuroscience",
- "issn": "1529-2401",
- "date": "2007-12-12",
- "abstract": "Expansion of a CAG repeat in the Huntington's disease (HD) gene results in progressive neuronal loss, particularly of striatal medium-sized spiny neurons (MSNs). Studies in human HD autopsy brain tissue, as well as cellular and animal models of HD, suggest that increased activity of NMDA-type glutamate receptors and altered mitochondrial function contribute to selective neuronal degeneration. In this regard, the YAC128 mouse model, expressing full-length human huntingtin with 128 glutamine repeats, has been the focus of much interest. Although NMDA-induced apoptosis is enhanced in YAC128 MSNs, here we report that the initial steps in the death signaling pathway, including NMDA receptor (NMDAR) current and cytosolic Ca2+ loading, are similar to those observed in wild-type MSNs. In contrast, we found that the NMDAR-mediated Ca2+ load triggered a strikingly enhanced loss of mitochondrial membrane potential in YAC128 MSNs, suggesting that NMDAR signaling via the mitochondrial apoptotic pathway is altered. This effect was accompanied by impaired cytosolic Ca2+ clearance after removal of NMDA, a difference that was not apparent after high potassium-evoked depolarization-mediated Ca2+ entry. Inhibition of the mitochondrial permeability transition (mPT) reduced peak cytosolic Ca2+ and mitochondrial depolarization evoked by NMDA in YAC128 MSNs but not wild-type MSNs. Hence, in contrast to YAC models with moderate CAG expansions, the enhanced NMDA-induced apoptosis in YAC128 MSNs is predominantly determined by augmented mitochondrial sensitivity to Ca2+-induced activation of the mPT. These results suggest that the CAG repeat length influences the mechanism by which mHtt enhances NMDAR-mediated excitotoxicity.",
+ "publisher": "Proceedings of the National Academy of Sciences of the United States of America",
+ "issn": "0027-8424",
+ "date": "2000-12-05",
+ "abstract": "Neural and stem cell transplantation is emerging as a potential treatment for neurodegenerative diseases. Transplantation of specific committed neuroblasts (fetal neurons) to the adult brain provides such scientific exploration of these new potential therapies. Huntington's disease (HD) is a fatal, incurable autosomal dominant (CAG repeat expansion of huntingtin protein) neurodegenerative disorder with primary neuronal pathology within the caudate-putamen (striatum). In a clinical trial of human fetal striatal tissue transplantation, one patient died 18 months after transplantation from cardiovascular disease, and postmortem histological analysis demonstrated surviving transplanted cells with typical morphology of the developing striatum. Selective markers of both striatal projection and interneurons such as dopamine and c-AMP-related phosphoprotein, calretinin, acetylcholinesterase, choline acetyltransferase, tyrosine hydroxylase, calbindin, enkephalin, and substance P showed positive transplant regions clearly innervated by host tyrosine hydroxylase fibers. There was no histological evidence of immune rejection including microglia and macrophages. Notably, neuronal protein aggregates of mutated huntingtin, which is typical HD neuropathology, were not found within the transplanted fetal tissue. Thus, although there is a genetically predetermined process causing neuronal death within the HD striatum, implanted fetal neural cells lacking the mutant HD gene may be able to replace damaged host neurons and reconstitute damaged neuronal connections. This study demonstrates that grafts derived from human fetal striatal tissue can survive, develop, and are unaffected by the disease process, at least for 18 months, after transplantation into a patient with HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18077673"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11106399"
},
{
- "id": "pmid:18068007",
+ "id": "pmid:11105061",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/18068007",
- "title": "Analysis of CCG repeats in Huntingtin gene among HD patients and normal populations in Japan.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11105061",
+ "title": "Huntington disease: DNA analysis in Brazilian population.",
"type": "article-journal",
- "doi": "10.1016/j.arcmed.2007.06.015",
+ "doi": "10.1590/s0004-282x2000000600001",
"authors": [
- ["Saeid", "Morovvati"],
- ["Masanori", "Nakagawa"],
- ["Mitsuhiro", "Osame"],
- ["Ali", "Karami"]
+ ["S", "Raskin"],
+ ["N", "Allan"],
+ ["H A", "Teive"],
+ ["F", "Cardoso"],
+ ["M S", "Haddad"],
+ ["G", "Levi"],
+ ["R", "Boy"],
+ ["J", "Lerena Junior"],
+ ["V S", "Sotomaior"],
+ ["M", "Janzen-D\u00fcck"],
+ ["L B", "Jardim"],
+ ["F R", "Fellander"],
+ ["L A", "Andrade"]
],
- "publisher": "Archives of medical research",
- "issn": "0188-4409",
- "date": "2007-08-23",
- "abstract": "Huntington's disease (HD) is a hereditary autosomal dominant neurodegenerative disease characterized by motor, cognitive, and psychiatric symptoms. The molecular basis of the disease is the expansion of the trinucleotide CAG in the first exon of a gene on chromosome four (4p 16.3). There is another triplet sequence, a CCG repeat, immediately 3' adjacent to the CAG repeat in Huntingtin. This triplet sequence is also polymorphic, alleles of 7 or 10 repeats are predominant in populations, and strong linkage disequilibrium between the CCG (7) allele and HD has been shown in western HD chromosomes, whereas Japanese HD chromosomes strongly associate with an allele of (CCG)10.",
+ "publisher": "Arquivos de neuro-psiquiatria",
+ "issn": "0004-282X",
+ "date": "2000-12-01",
+ "abstract": "Huntington disease (HD) is associated with expansions of a CAG trinucleotide repeat in the HD gene. Accurate measurement of a specific CAG repeat sequence in the HD gene in 92 Brazilian controls without HD, 44 Brazilian subjects with clinical findings suggestive of HD and 40 individuals from 6 putative HD families, showed a range from 7 to 33 repeats in normal subjects and 39 to 88 repeats in affected subjects. A trend between early age at onset of first symptoms and increasing number of repeats was seen. Major increase of repeat size through paternal inheritance than through maternal inheritance was observed. Data generated from this study may have significant implications for the etiology, knowledge of the incidence, diagnosis, prognosis, genetic counseling and treatment of HD Brazilian patients.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18068007"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11105061"
},
{
- "id": "pmid:17952586",
+ "id": "pmid:11063736",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/17952586",
- "title": "Huntington's disease and mitochondrial DNA deletions: event or regular mechanism for mutant huntingtin protein and CAG repeats expansion?!",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11063736",
+ "title": "Gender of the embryo contributes to CAG instability in transgenic mice containing a Huntington's disease gene.",
"type": "article-journal",
- "doi": "10.1007/s10571-007-9206-5",
+ "doi": "10.1093/hmg/9.18.2767",
"authors": [
- ["Mohammad Mehdi", "Banoei"],
- ["Massoud", "Houshmand"],
- ["Mehdi Shafa Shariat", "Panahi"],
- ["Parvin", "Shariati"],
- ["Maryam", "Rostami"],
- ["Masoumeh Dehghan", "Manshadi"],
- ["Tayebeh", "Majidizadeh"]
+ ["I V", "Kovtun"],
+ ["T M", "Therneau"],
+ ["C T", "McMurray"]
],
- "publisher": "Cellular and molecular neurobiology",
- "issn": "0272-4340",
- "date": "2007-10-20",
- "abstract": "The mitochondrial DNA (mtDNA) may play an essential role in the pathogenesis of the respiratory chain complex activities in neurodegenerative disorders such as Huntington's disease (HD). Research studies were conducted to determine the possible levels of mitochondrial defect (deletion) in HD patients and consideration of interaction between the expanded Huntingtin gene as a nuclear gene and mitochondria as a cytoplasmic organelle. To determine mtDNA damage, we investigated deletions based in four areas of mitochondrial DNA, in a group of 60 Iranian patients clinically diagnosed with HD and 70 healthy controls. A total of 41 patients out of 60 had CAG expansion (group A). About 19 patients did not show expansion but had the clinical symptoms of HD (group B). MtDNA deletions were classified into four groups according to size; 9 kb, 7.5 kb, 7 kb, and 5 kb. We found one of the four-mtDNA deletions in at least 90% of samples. Multiple deletions have also been observed in 63% of HD patients. None of the normal control (group C) showed mtDNA deletions. The sizes or locations of the deletions did not show a clear correlation with expanded CAG repeat and age in our samples. The study presented evidence that HD patients had higher frequencies of mtDNA deletions in lymphocytes in comparison to the controls. It is thus proposed that CAG repeats instability and mutant Htt are causative factor in mtDNA damage.",
+ "publisher": "Human molecular genetics",
+ "issn": "0964-6906",
+ "date": "2000-11-01",
+ "abstract": "Gender is known to influence the transmission of trinucleotide repeats in human disease. However, the molecular basis for the parent-of-origin effect associated with trinucleotide repeat expansion is not known. We have followed, during transmission, the fate of the CAG trinucleotide repeat in a transgene containing the exon 1 portion of the human Huntington's disease (HD) gene. Similar to humans, the mouse transmits expansions predominantly through the male germ line. Surprisingly, we find that the CAG repeat size of the mutant human HD gene is different in male and female progeny from identical fathers. Males predominantly expand the repeat whereas females predominantly contract the repeat. In contrast to the classic definition of imprinting, CAG expansion is influenced by the gender of the embryo. Our results raise the possibility that there are X- or Y-encoded factors that influence repair or replication of DNA in the embryo. Gender dependence in the embryo may explain why expansion in HD from premutation to disease primarily occurs through the paternal line.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17952586"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11063736"
},
{
- "id": "pmid:17947312",
+ "id": "pmid:11013077",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/17947312",
- "title": "Corticostriatal synaptic function in mouse models of Huntington's disease: early effects of huntingtin repeat length and protein load.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11013077",
+ "title": "Identification and characterization of the miniature pig Huntington's disease gene homolog: evidence for conservation and polymorphism in the CAG triplet repeat.",
"type": "article-journal",
- "doi": "10.1113/jphysiol.2007.142448",
+ "doi": "10.1006/geno.2000.6317",
"authors": [
- ["Austen J", "Milnerwood"],
- ["Lynn A", "Raymond"]
+ ["N", "Matsuyama"],
+ ["S", "Hadano"],
+ ["K", "Onoe"],
+ ["H", "Osuga"],
+ ["J", "Showguchi-Miyata"],
+ ["Y", "Gondo"],
+ ["J E", "Ikeda"]
],
- "publisher": "The Journal of physiology",
- "issn": "0022-3751",
- "date": "2007-10-18",
- "abstract": "Huntington's disease (HD) is an autosomal dominant, late onset, neurodegenerative disease characterized by motor deficits and dementia that is caused by expansion of a CAG repeat in the HD gene. Clinical manifestations result from selective neuronal degeneration of predominantly GABAergic striatal medium-sized spiny neurons (MSNs). A growing number of studies demonstrate that personality, mood and cognitive disturbances are some of the earliest signs of HD and may reflect synaptic dysfunction prior to neuronal loss. Previous studies in striatal MSNs demonstrated early alterations in NMDA-type glutamate receptor currents in several HD mouse models, as well as evidence for presynaptic dysfunction prior to disease manifestations in the R6/2 HD fragment mouse model. We have compared corticostriatal synaptic function in full-length, human HD gene-carrying YAC transgenic mice expressing a non-pathogenic CAG repeat (YAC18; control) with three increasingly severe variants of pathogenic HD gene-expressing mice (YAC72 and two different lines of YAC128), at ages that precede any detectable disease phenotype. We report presynaptic dysfunction and a propensity towards synaptic depression in YAC72 and YAC128 compared to YAC18 mice, and, in the most severe model, we also observed altered AMPA receptor function. When normalized to evoked AMPAR currents, postsynaptic NMDAR currents are augmented in all three pathogenic HD YAC variants. These findings demonstrate multiple perturbations to corticostriatal synaptic function in HD mice, furthering our understanding of the early effects of the HD mutation that may contribute to cognitive dysfunction, mood disorders and later development of more serious dysfunction. Furthermore, this study provides a set of neurophysiological sequelae against which to test and compare other mouse models and potential therapies in HD.",
+ "publisher": "Genomics",
+ "issn": "0888-7543",
+ "date": "2000-10-01",
+ "abstract": "Huntington's disease (HD) is associated with a significant expansion of a CAG trinucleotide repeat, which results in a lengthened polyglutamine tract in the single gene product, huntingtin, on human 4p16.3. We isolated cDNA clones that encompassed the entire coding sequence of the miniature pig HD gene (Sus HD) from two porcine testis cDNA libraries. The cDNA contig revealed a 12,749-nucleotide transcript coding for a 345-kDa protein (3139 amino acid residues), which exhibited 96% peptide sequence homology to human huntingtin. Northern blot analysis revealed that the Sus HD gene was ubiquitously expressed as two large transcripts of approximately 11 and 13 kb in size in all the tested tissues, much like the human HD gene. The CAG trinucleotide repeat was found to be interrupted by CAA triplets and to encode 17 or 18 consecutive glutamine residues. In our laboratory stock of miniature pig, three allotypes in the triplet repeat sequence were found. Thus, the Sus HD gene closely resembles its human counterpart in terms of sequence and expression pattern. In particular, human-miniature pig similarities in the normal length of the CAG triplet repeat as well as its repeat-number polymorphism may indicate that miniature pig would provide a good animal model for Huntington's disease.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17947312"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11013077"
},
{
- "id": "pmid:17726644",
+ "id": "pmid:11009201",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/17726644",
- "title": "Glutamate uptake is reduced in prefrontal cortex in Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11009201",
+ "title": "Environmental stimulation increases survival in mice transgenic for exon 1 of the Huntington's disease gene.",
"type": "article-journal",
- "doi": "10.1007/s11064-007-9463-1",
+ "doi": "10.1002/1531-8257(200009)15:5<925::aid-mds1025>3.0.co;2-z",
"authors": [
- ["Bj\u00f8rnar", "Hassel"],
- ["Shoshi", "Tessler"],
- ["Richard L M", "Faull"],
- ["Piers C", "Emson"]
+ ["R J", "Carter"],
+ ["M J", "Hunt"],
+ ["A J", "Morton"]
],
- "publisher": "Neurochemical research",
- "issn": "0364-3190",
- "date": "2007-08-29",
- "abstract": "Huntington's disease (HD) is caused by a CAG repeat expansion in the HD gene, but how this mutation causes neuronal dysfunction and degeneration is unclear. Inhibition of glutamate uptake, which could cause excessive stimulation of glutamate receptors, has been found in animals carrying very long CAG repeats in the HD gene. In seven HD patients with moderate CAG expansions (40-52), repeat expansion and HD grade at autopsy were strongly correlated (r=0.88, p=0.0002). Uptake of [(3)H]glutamate was reduced by 43% in prefrontal cortex, but the level of synaptic (synaptophysin, AMPA receptors) and astrocytic markers (GFAP, glutamate transporter EAAT1) were unchanged. Glutamate uptake correlated inversely with CAG repeat expansion (r= -0.82, p=0.015). The reducing agent dithiothreitol improved glutamate uptake in controls, but not in HD brains, suggesting irreversible oxidation of glutamate transporters in HD. We conclude that impairment of glutamate uptake may contribute to neuronal dysfunction and degeneration in HD.",
+ "publisher": "Movement disorders : official journal of the Movement Disorder Society",
+ "issn": "0885-3185",
+ "date": "2000-09-01",
+ "abstract": "Mice transgenic for the first exon of the human Huntington's disease (HD) gene carrying an expanded CAG repeat expansion (R6/2 line) develop a progressive neurologic phenotype with symptoms resembling those seen in HD. The overt symptoms of R6/2 mice worsen with age, resulting in a rapid decline in health and premature death between 13 and 18 weeks of age. In this study, we characterized the onset and progression of the overt phenotype in R6/2 mice and examined factors that affect the phenotype and life expectancy of these mice. In particular, the effects of altering home cage environment, through changing feeding regimes and providing environmental stimulation, were investigated. We show that changes in feeding regimes significantly improved the general well-being and life expectancy of R6/2 mice. Furthermore, we find that various forms of environmental stimulation, including regular behavioral testing, significantly improved the survival of R6/2 mice over and above that resulting from the enhanced feeding regime. The fact that environmental stimulation improves the health and life expectancy in R6/2 mice not only enables the mice to serve as more useful research tools, but also suggests that environmental stimulation may have a beneficial impact on the progression of HD in patients.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17726644"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11009201"
},
{
- "id": "pmid:17660463",
+ "id": "pmid:10980573",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/17660463",
- "title": "Factors associated with HD CAG repeat instability in Huntington disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/10980573",
+ "title": "Analysis of CAG and CCG repeats in Huntingtin gene among HD patients and normal populations of India.",
"type": "article-journal",
- "doi": "10.1136/jmg.2007.050930",
+ "doi": "10.1038/sj.ejhg.5200515",
"authors": [
- ["V C", "Wheeler"],
- ["F", "Persichetti"],
- ["S M", "McNeil"],
- ["J S", "Mysore"],
- ["S S", "Mysore"],
- ["M E", "MacDonald"],
- ["R H", "Myers"],
- ["J F", "Gusella"],
- ["N S", "Wexler"]
+ ["S", "Pramanik"],
+ ["P", "Basu"],
+ ["P K", "Gangopadhaya"],
+ ["K K", "Sinha"],
+ ["D K", "Jha"],
+ ["S", "Sinha"],
+ ["S K", "Das"],
+ ["B K", "Maity"],
+ ["S C", "Mukherjee"],
+ ["S", "Roychoudhuri"],
+ ["P P", "Majumder"],
+ ["N P", "Bhattacharyya"]
],
- "publisher": "Journal of medical genetics",
- "issn": "1468-6244",
- "date": "2007-07-27",
- "abstract": "The Huntington disease (HD) CAG repeat exhibits dramatic instability when transmitted to subsequent generations. The instability of the HD disease allele in male intergenerational transmissions is reflected in the variability of the CAG repeat in DNA from the sperm of male carriers of the HD gene.",
+ "publisher": "European journal of human genetics : EJHG",
+ "issn": "1018-4813",
+ "date": "2000-09-01",
+ "abstract": "We have analysed the distribution of CAG and adjacent polymorphic CCG repeats in the Huntingtin gene in 28 clinically diagnosed unrelated Huntington's disease (HD) patients and in normal individuals belonging to different ethnic groups of India. The range of expanded CAG repeats in HD patients varied from 41 to 56 repeats, whereas in normal individuals this number varied between 11 and 31 repeats. We identified six CCG alleles from a total of 380 normal chromosomes that were pooled across different ethnic populations of India. There were two predominant alleles: (CCG)7 (72.6%) and (CCG)10 (20%). We report here for the first time one four-repeat CCG allele which has not been found in any population so far. We found 30 haplotypes (two loci CAG-CCG) for 380 normal chromosomes. In the present study, no statistically significant preponderance of expanded HD alleles was found on either (CCG)7 or (CCG)10 backgrounds. Our studies suggest that the overall prevalence of HD in Indian populations may not be as high as in Western populations. Further studies are necessary to identify the origin of HD mutation in these populations.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17660463"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10980573"
},
{
- "id": "pmid:17653603",
+ "id": "pmid:10814708",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/17653603",
- "title": "Survival of Huntington's disease patients in Serbia: longer survival in female patients.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/10814708",
+ "title": "Decreased expression of striatal signaling genes in a mouse model of Huntington's disease.",
"type": "article-journal",
- "doi": "10.1007/s10654-007-9157-7",
+ "doi": "10.1093/hmg/9.9.1259",
"authors": [
- ["Tatjana", "Pekmezovic"],
- ["Marina", "Svetel"],
- ["Jelena", "Maric"],
- ["Irena", "Dujmovic-Basuroski"],
- ["Natasa", "Dragasevic"],
- ["Milica", "Keckarevic"],
- ["Stanka", "Romac"],
- ["Vladimir S", "Kostic"]
+ ["R", "Luthi-Carter"],
+ ["A", "Strand"],
+ ["N L", "Peters"],
+ ["S M", "Solano"],
+ ["Z R", "Hollingsworth"],
+ ["A S", "Menon"],
+ ["A S", "Frey"],
+ ["B S", "Spektor"],
+ ["E B", "Penney"],
+ ["G", "Schilling"],
+ ["C A", "Ross"],
+ ["D R", "Borchelt"],
+ ["S J", "Tapscott"],
+ ["A B", "Young"],
+ ["J H", "Cha"],
+ ["J M", "Olson"]
],
- "publisher": "European journal of epidemiology",
- "issn": "0393-2990",
- "date": "2007-07-25",
- "abstract": "The objective of this study was to estimate probability of survival of Huntington's disease (HD) patients in Serbia as a function of CAG repeat length and selected demographic variables. This follow-up study was carried out at the Institute of Neurology, Clinical Centre of Serbia, Belgrade, 1982-2004. The study group consisted of 112 HD patients. The significant inverse correlation was found between CAG repeat length and age at onset of HD (r = -0.732, P = 0.001) and age at death (r = -0.760, P = 0.001). The cumulative probabilities of survival in a five, ten, fifteen, and twenty-years' period were 90.9, 63.2, 10.3 and 4.5%, respectively. Higher survival probabilities were registered in female patients, as well as in those with older age at onset and lower number of CAG repeat length ( or = Vonsattel et al's grade I, five patients lacking striatal tissue for review, and two at-risk individuals with grade 0 and grade I HD pathology, respectively. One patient with HD-like pathology and two patients and four at-risk individuals without HD pathology lacked HD inclusions. In the genetically analyzed cases, the inclusions were exclusively and consistently observed in association with repeat expansion [(CAG)(n) > or = 39, n = 81]. Thirteen inclusion-positive cases, including the grade 0 at-risk individual, had a false negative original pathological diagnosis of HD and four had an unjustly questionable diagnosis. A false positive diagnosis was made in the inclusion-negative case with HD-like pathology. These results indicate that immunohistochemical analysis for HD inclusions facilitates the pathological evaluation of HD and enhances its accuracy.",
+ "publisher": "Zhonghua yi xue za zhi = Chinese medical journal; Free China ed",
+ "issn": "0578-1337",
+ "date": "1999-09-01",
+ "abstract": "Uncertainty in diagnosing Huntington's disease (HD) may occur in the absence of a family history or typical movement disorders. HD is characterized by a progressive disturbance of typical movement disorders (i.e., chorea, athetosis), psychiatric symptoms (i.e., depression, insomnia, anxiety, suspiciousness), and cognitive deterioration, in the absence of a dominant family history of similar disorders. Often, some of these symptoms are missing, which makes the diagnosis difficult. In recent years molecular testing has become the gold standard for diagnosing HD. Diagnostic accuracy for HD on genetic screening of patients and their families is important. We evaluated a polymerase chain reaction (PCR) technique for the detection of CAG trinucleotide repeats in the Huntington IT15 gene on chromosome 4 for the diagnosis of HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17493035"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10502848"
},
{
- "id": "pmid:17478887",
+ "id": "pmid:10502825",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/17478887",
- "title": "Decreased VIP and VPAC2 receptor expression in the biological clock of the R6/2 Huntington's disease mouse.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/10502825",
+ "title": "Increased apoptosis of Huntington disease lymphoblasts associated with repeat length-dependent mitochondrial depolarization.",
"type": "article-journal",
- "doi": "10.1385/jmn/31:02:139",
+ "doi": "10.1038/13518",
"authors": [
- ["Jan", "Fahrenkrug"],
- ["Natalija", "Popovic"],
- ["Birgitte", "Georg"],
- ["Patrik", "Brundin"],
- ["Jens", "Hannibal"]
+ ["A", "Sawa"],
+ ["G W", "Wiegand"],
+ ["J", "Cooper"],
+ ["R L", "Margolis"],
+ ["A H", "Sharp"],
+ ["J F", "Lawler"],
+ ["J T", "Greenamyre"],
+ ["S H", "Snyder"],
+ ["C A", "Ross"]
],
- "publisher": "Journal of molecular neuroscience : MN",
- "issn": "0895-8696",
- "date": "2007-01-01",
- "abstract": "Huntington's disease (HD) is a fatal genetic neurodegenerative disorder caused by a CAG triplet repeat expansion in the gene encoding the protein huntingtin. The most studied model of HD, the R6/2 transgenic mouse, replicates many features of the disease. In addition to motor, cognitive, and endocrine dysfunctions, these mice exhibit a progressive disruption of circadian rhythms. This is accompanied by an altered expression of the circadian clock genes in the suprachiasmatic nucleus/nuclei (SCN), the principal circadian pacemaker in the brain. The neuropeptide vasoactive intestinal polypeptide (VIP) and its receptor VPAC2 are highly expressed in the SCN, and VIPergic signaling plays an essential role in maintenance of ongoing circadian rhythmicity. We found a marked reduction in both VIP mRNA and VPAC2 receptor mRNA, quantified by RT-PCR, as well as a decrease in VIP immunostaining in the SCN of R6/2 mice. These changes were coupled to a disruption of circadian rhythm. We observed no loss of neurons in the SCN and therefore suggest that the changes in VIP and VPAC2 receptor are due to their decreased expression. In conclusion, we propose that impaired VIPergic signaling is an additional candidate mechanism for disruption of circadian rhythms in R6/2 mice.",
+ "publisher": "Nature medicine",
+ "issn": "1078-8956",
+ "date": "1999-10-01",
+ "abstract": "Huntington disease (HD) is a genetically dominant condition caused by expanded CAG repeats coding for glutamine in the HD gene product huntingtin. Although HD symptoms reflect preferential neuronal death in specific brain regions, huntingtin is expressed in almost all tissues, so abnormalities outside the brain might be expected. Although involvement of nuclei and mitochondria in HD pathophysiology has been suggested, specific intracellular defects that might elicit cell death have been unclear. Mitochondria dysfunction is reported in HD brains; mitochondria are organelles that regulates apoptotic cell death. We now report that lymphoblasts derived from HD patients showed increased stress-induced apoptotic cell death associated with caspase-3 activation. When subjected to stress, HD lymphoblasts also manifested a considerable increase in mitochondrial depolarization correlated with increased glutamine repeats.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17478887"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10502825"
},
{
- "id": "pmid:17383831",
+ "id": "pmid:10434306",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/17383831",
- "title": "Haploinsufficiency of yeast FEN1 causes instability of expanded CAG/CTG tracts in a length-dependent manner.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/10434306",
+ "title": "Analysis of the subcellular localization of huntingtin with a set of rabbit polyclonal antibodies in cultured mammalian cells of neuronal origin: comparison with the distribution of huntingtin in Huntington's disease autopsy brain.",
"type": "article-journal",
- "doi": "10.1016/j.gene.2007.01.025",
+ "doi": "10.1098/rstb.1999.0459",
"authors": [
- ["Jiahui", "Yang"],
- ["Catherine H", "Freudenreich"]
+ ["J C", "Dorsman"],
+ ["M A", "Smoor"],
+ ["M L", "Maat-Schieman"],
+ ["M", "Bout"],
+ ["S", "Siesling"],
+ ["S G", "van Duinen"],
+ ["J J", "Verschuuren"],
+ ["J T", "den Dunnen"],
+ ["R A", "Roos"],
+ ["G J", "van Ommen"]
],
- "publisher": "Gene",
- "issn": "0378-1119",
- "date": "2007-02-12",
- "abstract": "Trinucleotide repeat diseases, such as Huntington's disease, are caused by the expansion of trinucleotide repeats above a threshold of about 35 repeats. Once expanded, the repeats are unstable and tend to expand further both in somatic cells and during transmission, resulting in a more severe disease phenotype. Flap endonuclease 1 (Fen1), has an endonuclease activity specific for 5' flap structures and is involved in Okazaki fragment processing and base excision repair. Fen1 also plays an important role in preventing instability of CAG/CTG trinucleotide repeat sequences, as the expansion frequency of CAG/CTG repeats is increased in FEN1 mutants in vitro and in yeast cells defective for the yeast homolog, RAD27. Here we have tested whether one copy of yeast FEN1 is enough to maintain CAG/CTG tract stability in diploid yeast cells. We found that CAG/CTG repeats are stable in RAD27 +/- cells if the tract is 70 repeats long and exhibit a slightly increased expansion frequency if the tract is 85 or 130 repeats long. However for CAG-155 tracts, the repeat expansion frequency in RAD27 +/- cells is significantly higher than in RAD27 +/+ cells. This data indicates that cells containing longer CAG/CTG repeats need more Fen1 protein to maintain tract stability and that maintenance of long CAG/CTG repeats is particularly sensitive to Fen1 levels. Our results may explain the relatively small effects seen in the Huntington's disease (HD) FEN1 +/- heterozygous mice and myotonic dystrophy type 1 (DM1) FEN1 +/- heterozygous mice, and suggest that inefficient flap processing by Fen1 could play a role in the continued expansions seen in humans with trinucleotide repeat expansion diseases.",
+ "publisher": "Philosophical transactions of the Royal Society of London. Series B, Biological sciences",
+ "issn": "0962-8436",
+ "date": "1999-06-29",
+ "abstract": "Huntington's disease (HD) is a neurodegenerative disorder with a midlife onset. The disease is caused by expansion of a CAG (glutamine) repeat within the coding region of the HD gene. The molecular mechanism by which the mutated protein causes this disease is still unclear. To study the protein we have generated a set of rabbit polyclonal antibodies raised against different segments of the N-terminal, central and C-terminal parts of the protein. The polyclonal antibodies were affinity purified and characterized in ELISA and Western blotting experiments. All antibodies can react with mouse and human proteins. The specificity of these antibodies is underscored by their recognition of huntingtin with different repeat sizes in extracts prepared from patient-derived lymphoblasts. The antibodies were used in immunofluorescence experiments to study the subcellular localization of huntingtin in mouse neuroblastoma NIE-115 cells. The results indicate that most huntingtin is present in the cytoplasm, whereas a minor fraction is present in the nucleus. On differentiation of the NIE-115 cells in vitro, the subcellular distribution of huntingtin does not change significantly. These results suggest that full-length huntingtin with a normal repeat length can be detected in the nucleus of cycling and non-cycling cultured mammalian cells of neuronal origin. However, in HD autopsy brain the huntingtin-containing neuronal intranuclear inclusions can be detected only with antibodies raised against the N-terminus of huntingtin. Thus several forms of huntingtin display the propensity for nuclear localization, possibly with different functional consequences.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17383831"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10434306"
},
{
- "id": "pmid:17363167",
+ "id": "pmid:10434303",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/17363167",
- "title": "Plasma neurofilament heavy chain levels in Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/10434303",
+ "title": "Transgenic mice expressing mutated full-length HD cDNA: a paradigm for locomotor changes and selective neuronal loss in Huntington's disease.",
"type": "article-journal",
- "doi": "10.1016/j.neulet.2007.02.053",
+ "doi": "10.1098/rstb.1999.0456",
"authors": [
- ["Edward J", "Wild"],
- ["Axel", "Petzold"],
- ["Geoff", "Keir"],
- ["Sarah J", "Tabrizi"]
+ ["P H", "Reddy"],
+ ["V", "Charles"],
+ ["M", "Williams"],
+ ["G", "Miller"],
+ ["W O", "Whetsell"],
+ ["D A", "Tagle"]
],
- "publisher": "Neuroscience letters",
- "issn": "0304-3940",
- "date": "2007-02-24",
- "abstract": "There is a need for biomarkers of onset and progression in Huntington's disease (HD), as current outcome measures lack the reliability to enable the efficient conduct of disease-modifying trials. Neurofilament heavy chain (NfH) is a neuron-specific protein for the neuro-axonal compartment that has been proposed as a marker for axonal injury, degeneration and loss and its clinical use as a biomarker has been suggested in several neurodegenerative diseases. We used an enzyme-linked immunosorbent assay to quantify NfH levels in plasma in control subjects, premanifest HD mutation carriers and subjects with early and moderate manifest HD. We found no correlation between plasma NfH level and disease stage, or calculated parameters based on CAG repeat length, the major determinant of disease course in HD, and no evidence that NfH may be a predictor of disease onset. We conclude that plasma NfH concentration is not a useful biomarker of onset or progression in HD.",
+ "publisher": "Philosophical transactions of the Royal Society of London. Series B, Biological sciences",
+ "issn": "0962-8436",
+ "date": "1999-06-29",
+ "abstract": "Huntington's disease (HD) is a progressive neurodegenerative disorder characterized clinically by motor and psychiatric disturbances and pathologically by neuronal loss and gliosis (reactive astrocytosis) particularly in the striatum and cerebral cortex. We have recently created HD full-length cDNA transgenic mouse models that may serve as a paradigm for HD. A more detailed characterization of these models is presented here. The transgene encoding normal huntingtin consists of 9417 bp of the huntingtin coding sequences including 16 tandem CAGs coding for polyglutamines as part of exon 1. The transgene is driven by a heterologous cytomegalovirus promoter. Five independent transgenic mouse lines were obtained using this construct. An additional six transgenic lines were obtained using full-length HD constructs that have been modified to include either 48 or 89 CAG repeat expansions. Southern blot and densitometric analyses indicated unique integration sites for the transgene in each of the lines with a copy number ranging from two to 22 copies. Widespread expression of the transgene in brain, heart, spleen, kidney, lung, liver and gonads from each line was determined by Western blot analyses. In the brain, transgene expression was found in cerebral cortex, striatum, hippocampus and cerebellum. Expression of the transgene was as much as five times the endogenous mouse huntingtin level. Phenotypically, only mice expressing 48 or 89 CAG repeats manifested progressive behavioural and motor dysfunction. Early behavioural abnormalities were characterized by trunk curling and clasping of both fore- and hindlimbs when the animals were suspended by their tails. Subsequently, these mice exhibited hyperkinetic movements, including heightened exploratory activities, unidirectional rotational behaviour, backflipping and excessive grooming that lasted for several weeks. Eventually, the animals progressed to a hypokinetic phase consisting of slowed movements and lack of response to sensory stimuli. Urine retention or incontinence was also a prominent feature of the hypokinetic phase. At the end stage of the disease process, HD48(B,D) and HD89(A-C) mice became akinetic just prior to death. Neuropathological examination of mice at various stages indicated that it was only during the hypokinetic phase and thereafter when selective neuronal loss was most apparent. Regions of neurodegeneration and loss included the striatum, cerebral cortex, thalamus and hippocampus. TUNEL staining indicated an apoptotic mode of cell death in these brain regions. Comparative neuronal counts after Nissl staining showed as much as 20% loss of small and medium neurons in the striatum in mice at the hypokinetic and akinetic stages. Reactive astrocytosis accompanied the areas of neurodegeneration and loss. Polyglutamine aggregates in the form of neuronal intranuclear inclusions and diffuse nuclear and perinuclear aggregations were found in a small percentage of neurons, including those in brain regions that are typically spared in HD. This observation suggests that polyglutamine aggregates may not be sufficient to cause neuronal loss in HD. In both behavioural and neuropathological analyses, wild-type and transgenic animals with 16 CAG repeats were indistinguishable from each other and do not exhibit the changes observed for mice carrying the 48 and 89 CAG repeat mutations. Thus, animals expressing the CAG repeat expansions appear to represent clinically analogous models for HD pathogenesis, and may also provide insights into the underlying pathophysiological mechanisms of other triplet repeat disorders.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17363167"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10434303"
},
{
- "id": "pmid:17356014",
+ "id": "pmid:10398087",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/17356014",
- "title": "Extended polyglutamine repeats trigger a feedback loop involving the mitochondrial complex III, the proteasome and huntingtin aggregates.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/10398087",
+ "title": "Frequent expansion of Epstein-Barr virus (EBV) infected cells in germinal centres of tonsils from an area with a high incidence of EBV-associated lymphoma.",
"type": "article-journal",
- "doi": "10.1093/hmg/ddm023",
+ "doi": "10.1002/(sici)1096-9896(199902)187:3<326::aid-path242>3.0.co;2-n",
"authors": [
- ["Hirokazu", "Fukui"],
- ["Carlos T", "Moraes"]
+ ["I", "Araujo"],
+ ["H D", "Foss"],
+ ["M", "Hummel"],
+ ["I", "Anagnostopoulos"],
+ ["H S", "Barbosa"],
+ ["A", "Bittencourt"],
+ ["H", "Stein"]
],
- "publisher": "Human molecular genetics",
- "issn": "0964-6906",
- "date": "2007-03-13",
- "abstract": "Mitochondrial abnormalities represent a major cytopathology in Huntington's disease (HD), a fatal neurodegenerative disease caused by CAG repeat expansions in the gene encoding huntingtin (Htt). In the present study, we investigated whether defects in the mitochondrial respiratory function are consequences of the expression of mutant Htt or they promote the formation of Htt aggregates. To take advantage of existing mitochondrial DNA mutants, we developed human osteosarcoma 143B cells expressing mutant Htt in an inducible manner and found that cells expressing mutant Htt but not wild-type Htt exhibited a reduced activity of complex III and an increased activity of complex IV. Conversely, pharmacological treatments that inhibited complex III activity significantly promoted the formation of Htt aggregates. This complex III-mediated modulation of Htt aggregates was also observed in a neuronal progenitor RN33B cell line transduced by lentivirus carrying mutant Htt. This effect of complex III inhibition on the Htt aggregates appeared to be mediated by the inhibition of proteasome activity, but not by ATP depletion or production of reactive oxygen species. Accordingly, complex III mutant cells also showed decreased proteasome activity. These results suggest the presence of a feedback system connecting the mitochondrial respiratory complex III and the production of Htt aggregates. Our results suggest that therapeutic interventions targeting complex III and/or proteasome could ameliorate the progress of HD.",
+ "publisher": "The Journal of pathology",
+ "issn": "0022-3417",
+ "date": "1999-02-01",
+ "abstract": "Burkitt's lymphoma (BL) and Hodgkin's disease (HD) occurring in developing regions are frequently associated with Epstein-Barr virus (EBV) infection and have a high incidence in childhood. Recent genotyping studies indicate that the tumour cells of both neoplasms represent B cells that contain somatically mutated immunoglobulin heavy chain genes. This implies that the precursors of these neoplasms have participated in the germinal centre (GC) reaction. We therefore presumed that normal lymphoid tissues from children living in developing regions would harbour an increased number of EBV-infected cells within the GC, when compared with children living in industrialized nations. To test this hypothesis, hyperplastic tonsils from 40 children living in Bahia (Brazil) and 40 from German children were analysed for the presence of EBV-encoded small nuclear RNA (EBER) and EBV-encoded proteins by in situ hybridization and immunohistology, respectively. Although the overall EBV infection rate was similar in both groups (50 per cent of Bahian vs. 45 per cent of German cases), a significantly higher number of EBER-positive lymphoid cells were found in the GCs of 8/20 EBV-positive tonsils from Brazil (9-89 cells/GC; mean: 14.5 cells/GC per case), while only 3/18 tonsils from Germany displayed a few EBER positive cells (1-9 cells/GC; mean: 0.5 cell/GC per case) in this compartment (p < 0.007). In addition, the EBV-infected GC cells in Bahian samples resembled centroblasts, exhibited mitotic activity, and in two cases showed expression of EBV-encoded latent membrane protein (LMP)-1, findings not present in German samples. These data show that latently EBV-infected cells participate more frequently in GC reactions in developing regions than in industrialized countries and may abnormally express the oncogenic protein LMP-1. This could in part explain the higher incidence in this region of EBV association with lymphomas related to GC cells or their progeny, such as BL and HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17356014"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10398087"
},
{
- "id": "pmid:17352930",
+ "id": "pmid:10334474",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/17352930",
- "title": "Genetic criteria for Huntington's disease pathogenesis.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/10334474",
+ "title": "Accurate determination of the number of CAG repeats in the Huntington disease gene using a sequence-specific internal DNA standard.",
"type": "article-journal",
- "doi": "10.1016/j.brainresbull.2006.10.014",
+ "doi": "10.1034/j.1399-0004.1999.550308.x",
"authors": [
- ["James F", "Gusella"],
- ["Marcy", "Macdonald"]
+ ["O", "Bruland"],
+ ["E W", "Almqvist"],
+ ["Y P", "Goldberg"],
+ ["H", "Boman"],
+ ["M R", "Hayden"],
+ ["P M", "Knappskog"]
],
- "publisher": "Brain research bulletin",
- "issn": "0361-9230",
- "date": "2006-11-15",
- "abstract": "Genetic analysis aims to identify the variations in DNA sequence whose functional consequences produce heritable variations in phenotype. In one of the first successes of unbiased molecular genetic analysis in human disease, the Huntington's disease (HD) gene was mapped and cloned without any prior knowledge of the nature of its protein product or of the molecular defect that underlies the characteristic phenotype of the disorder. However, while the cloning of HD and recognition of its trinucleotide repeat expansion spawned a plethora of approaches to investigating HD through its distinctive neuropathology, the role for genetic strategies in HD research did not end there. The use of genetic analysis has remained a critical tool for defining the characteristics of the mechanism that triggers the pathogenic process, permitting the investigation of early events that occur long before traditionally recognized pathology. Delineation of these events can reveal molecular targets for development of therapies that prevent onset of HD. Most recently, an extension of genetic analysis to the identification of non-linked genetic variations that alter the course of HD pathogenesis has offered the promise of identifying modifier genes to reveal biological pathways active throughout the disease process and to provide valid targets for pharmacological intervention. Thus, unbiased genetic strategies have not only provided a crucial entr\u00e9e into molecular investigation of HD via a root cause that was previously unsuspected, they also represent a continuing route to accelerate the ultimate goal of developing an effective treatment for HD.",
+ "publisher": "Clinical genetics",
+ "issn": "0009-9163",
+ "date": "1999-03-01",
+ "abstract": "We have developed a sequence-specific internal DNA size standard for the accurate determination of the number of CAG repeats in the Huntington disease (HD) gene by cloning key fragments (between 15 and 64 CAG repeats) of the HD gene. These fragments, pooled to produce a sequence-specific DNA ladder, enabled us to observe the true number of CAG repeats directly, with no need for calculations. Comparison of the calculated numbers of CAG repeats in the HD gene using this sequence-specific DNA standard with a commercially available standard (GENESCAN-500 TAMRA) showed that the latter underestimated the number of CAG repeats by three when analyzed by capillary electrophoresis on the ABI 310 Genetic Analyzer (POP4 polymer). In contrast, the use of the same standard overestimated the number of CAG repeats by one when the samples were analyzed by denaturing polyacrylamide electrophoresis on ABI 377 DNA Sequencer (6% denaturing polyacrylamide gel). This suggests that our sequence-specific standard provides greater accuracy for the determination of the true number of CAG repeats in the HD gene than commercially available standards. The sequence-specific standard can be radioactively labeled and successfully replace conventional DNA size standards when analyzing polymerase chain reaction (PCR)-amplified HD alleles by denaturing polyacrylamide electrophoresis.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17352930"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10334474"
},
{
- "id": "pmid:17307423",
+ "id": "pmid:10333377",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/17307423",
- "title": "Repeat length polymorphism of the serotonin transporter gene influences pulmonary artery pressure in heart failure.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/10333377",
+ "title": "Behavioral effects of tryptophan depletion in seasonal affective disorder associated with the serotonin transporter gene?",
"type": "article-journal",
- "doi": "10.1016/j.ahj.2006.12.011",
+ "doi": "10.1016/s0165-1781(99)00009-8",
"authors": [
- ["Thomas P", "Olson"],
- ["Eric M", "Snyder"],
- ["Robert P", "Frantz"],
- ["Stephen T", "Turner"],
- ["Bruce D", "Johnson"]
+ ["E", "Lenzinger"],
+ ["A", "Neumeister"],
+ ["N", "Praschak-Rieder"],
+ ["K", "Fuchs"],
+ ["E", "Gerhard"],
+ ["M", "Willeit"],
+ ["W", "Sieghart"],
+ ["S F", "Kasper"],
+ ["K", "Hornik"],
+ ["H N", "Aschauer"]
],
- "publisher": "American heart journal",
- "issn": "1097-6744",
- "date": "2007-03-01",
- "abstract": "Pulmonary hypertension is common in patients with heart failure (HF); however, for a given degree of left ventricular dysfunction, the range in pulmonary artery pressures (PAPs) is large. Polymorphisms of the serotonin transporter (5-HTT) gene have been implicated in contributing to smooth muscle dysfunction and remodeling of the pulmonary vasculature. This study examined the influence of a repeat length polymorphism in the promoter region of the 5-HTT gene on PAP between patients with HF and healthy control participants.",
+ "publisher": "Psychiatry research",
+ "issn": "0165-1781",
+ "date": "1999-03-22",
+ "abstract": "There is some evidence that the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) may be involved in the pathogenesis of seasonal affective disorder (SAD). Short-term tryptophan (TRP) depletion was carried out in 18 drug-free remitted patients who met DSM-IV criteria for SAD. Behavioral effects were measured with the Hamilton Depression Rating Scale (HDRS) both 24 h before and 24 h after TRP depletion. Some of the patients showed behavioral responses such as lowered mood, feelings of guilt, loss of interest, agitation, loss of energy, fatigue, social withdrawal, increased appetite, and carbohydrate craving. It was the aim of our study to investigate whether the genotypes of the serotonin transporter gene were associated with symptoms of transient depressive relapse after TRP depletion. In addition, we matched the SAD patients with healthy control subjects to see if alleles and genotypes of the serotonin transporter gene were associated with SAD. High molecular weight DNA was isolated from peripheral blood leukocytes using standard methods. For the 5-HTT receptor gene, a 17-bp repetitive element of intron 2 was genotyped (variable number tandem repeat, VNTR). Alterations in HDRS scores after TRP depletion showed no significant association with alleles or genotypes of the 5-HTT gene, although heterozygotes showed a trend toward increased HDRS scores. The serotonin transporter is known to play a critical role in the termination of serotonergic neurotransmission by sodium-dependent uptake of 5-HT into the presynaptic neuron. The present study in a small group of SAD patients was unable to demonstrate that the 5-HTT gene plays a role in the pathogenesis of SAD or in short-term depressive relapse after TRP depletion.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17307423"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10333377"
},
{
- "id": "pmid:17299512",
+ "id": "pmid:10196365",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/17299512",
- "title": "Monoamine metabolites level in CSF is related to the 5-HTT gene polymorphism in treatment-resistant depression.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/10196365",
+ "title": "A Huntington's disease CAG expansion at the murine Hdh locus is unstable and associated with behavioural abnormalities in mice.",
"type": "article-journal",
- "doi": "10.1038/sj.npp.1301336",
+ "doi": "10.1093/hmg/8.5.763",
"authors": [
- ["Ikuko", "Kishida"],
- ["Eleni", "Aklillu"],
- ["Chiaki", "Kawanishi"],
- ["Leif", "Bertilsson"],
- ["Hans", "Agren"]
+ ["P F", "Shelbourne"],
+ ["N", "Killeen"],
+ ["R F", "Hevner"],
+ ["H M", "Johnston"],
+ ["L", "Tecott"],
+ ["M", "Lewandoski"],
+ ["M", "Ennis"],
+ ["L", "Ramirez"],
+ ["Z", "Li"],
+ ["C", "Iannicola"],
+ ["D R", "Littman"],
+ ["R M", "Myers"]
],
- "publisher": "Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology",
- "issn": "0893-133X",
- "date": "2007-02-14",
- "abstract": "The serotonin (5-hydroxytryptamine) transporter (5-HTT) is considered to affect the pathogenesis of mood disorders. Large number of genetic association studies between 5-HTT functional polymorphisms and vulnerability of mood disorders and therapeutic response to antidepressants has been carried out. We investigated the influence of 5-HTT-linked polymorphic region (5-HTTLPR) and 5-HTT 17 bp variable number of tandem repeat polymorphism (5-HTTVNTR) polymorphisms on concentrations of monoamine metabolites in cerebrospinal fluid (CSF) among treatment-resistant patients with mood disorders. Subjects were 119 Swedish patients with persistent mood disorders and 141 healthy subjects. In 112 of these patients, we measured 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol in CSF. Genotyping for 5-HTT polymorphisms from genomic DNA was carried out by PCR. There was no significant difference in allele/genotype frequency between patients and healthy subjects. In patients with mood disorders, we found significant difference in mean 5-HIAA concentration between 5-HTTLPR genotypes (p=0.03). Although the 5-HIAA concentration showed a tendency to be higher in short (S) carriers than in non-S carriers of the 5-HTTLPR in patients (p=0.06), when considering patients with major depressive disorder (MDD), the 5-HIAA concentration was significantly higher among S carriers than among non-S carriers (p=0.02). Moreover, the 5-HIAA concentration was higher in S/S subjects compared to long (L)/L (p=0.0001) and L/S (p=0.002) subjects in patients with MDD. Similarly, there was higher HVA concentration in S/S subjects compared to L/L (p=0.002) and L/S subjects (p=0.002). There was no effect of 5-HTTVNTR. Our findings show that the 5-HTTLPR polymorphism affects 5-HIAA and HVA concentrations among treatment-resistant patients with mood disorders.",
+ "publisher": "Human molecular genetics",
+ "issn": "0964-6906",
+ "date": "1999-05-01",
+ "abstract": "Huntington's disease (HD) is a dominant disorder characterized by premature and progressive neurodegeneration. In order to generate an accurate model of the disease, we introduced an HD-like mutation (an extended stretch of 72-80 CAG repeats) into the endogenous mouse Hdh gene. Analysis of the mutation in vivo reveals significant levels of germline instability, with expansions, contractions and sex-of-origin effects in evidence. Mice expressing full-length mutant protein display abnormal social behaviour in the absence of acute neurodegeneration. Given that psychiatric changes, including irritability and aggression, are common findings in HD patients, our data are consistent with the hypothesis that some clinical features of HD may be caused by pathological processes that precede gross neuronal cell death. This implies that effective treatment of HD may require an understanding and amelioration of these dysfunctional processes, rather than simply preventing the premature death of neurons in the brain. These mice should facilitate the investigation of the molecular mechanisms that underpin the pathway from genotype to phenotype in HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17299512"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10196365"
},
{
- "id": "pmid:17181545",
+ "id": "pmid:10098889",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/17181545",
- "title": "The relationship between CAG repeat length and age of onset differs for Huntington's disease patients with juvenile onset or adult onset.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/10098889",
+ "title": "Brain neurotransmitter deficits in mice transgenic for the Huntington's disease mutation.",
"type": "article-journal",
- "doi": "10.1111/j.1469-1809.2006.00335.x",
+ "doi": "10.1046/j.1471-4159.1999.721773.x",
"authors": [
- ["J Michael", "Andresen"],
- ["Javier", "Gay\u00e1n"],
- ["Luc", "Djouss\u00e9"],
- ["Simone", "Roberts"],
- ["Denise", "Brocklebank"],
- ["Stacey S", "Cherny"],
- ["Lon R", "Cardon"],
- ["James F", "Gusella"],
- ["Marcy E", "MacDonald"],
- ["Richard H", "Myers"],
- ["David E", "Housman"],
- ["Nancy S", "Wexler"]
+ ["G P", "Reynolds"],
+ ["C F", "Dalton"],
+ ["C L", "Tillery"],
+ ["L", "Mangiarini"],
+ ["S W", "Davies"],
+ ["G P", "Bates"]
],
- "publisher": "Annals of human genetics",
- "issn": "0003-4800",
- "date": "2006-12-19",
- "abstract": "Age of onset for Huntington's disease (HD) varies inversely with the length of the disease-causing CAG repeat expansion in the HD gene. A simple exponential regression model yielded adjusted R-squared values of 0.728 in a large set of Venezuelan kindreds and 0.642 in a North American, European, and Australian sample (the HD MAPS cohort). We present evidence that a two-segment exponential regression curve provides a significantly better fit than the simple exponential regression. A plot of natural log-transformed age of onset against CAG repeat length reveals this segmental relationship. This two-segment exponential regression on age of onset data increases the adjusted R-squared values by 0.012 in the Venezuelan kindreds and by 0.035 in the HD MAPS cohort. Although the amount of additional variance explained by the segmental regression approach is modest, the two slopes of the two-segment regression are significantly different from each other in both the Venezuelan kindreds [F(2, 439) = 11.13, P= 2 x 10(-5)] and in the HD MAPS cohort [F(2, 688) = 38.27, P= 2 x 10(-16)]. In both populations, the influence of each CAG repeat on age of onset appears to be stronger in the adult-onset range of CAG repeats than in the juvenile-onset range.",
+ "publisher": "Journal of neurochemistry",
+ "issn": "0022-3042",
+ "date": "1999-04-01",
+ "abstract": "Huntington's disease (HD) is associated with an expansion in the CAG repeat sequence of a gene on chromosome 4, resulting in a neurodegenerative process particularly affecting the striatum and with profound but selective changes in content of various neurotransmitters. Recently, transgenic mice expressing a fragment of the human HD gene containing a large CAG expansion have been generated; these mice exhibit a progressive neurological phenotype that includes motor disturbances, as well as neuronal deficits. To investigate their underlying neurotransmitter pathology, we have determined concentrations of GABA, glutamate, and the monoamine neurotransmitters in several brain regions in these mice and control animals at times before and after the emergence of the behavioural phenotype. In contrast to the findings in HD, striatal GABA was unaffected, although a deficit was observed in the cerebellum, consistent with a dysfunction of Purkinje cells. Losses of the monoamine transmitters were observed, some of which are not seen in HD. Thus, 5-hydroxytryptamine and, to a greater extent, 5-hydroxyindoleacetic acid levels were diminished in all brain regions studied, and noradrenaline was particularly affected in the hippocampus. Dopamine was decreased in the striatum in older animals, parallelling evidence for diminished dopaminergic activity in HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17181545"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10098889"
},
{
- "id": "pmid:17174018",
+ "id": "pmid:10051007",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/17174018",
- "title": "Association between obsessive-compulsive disorder and a variable number of tandem repeats polymorphism in intron 2 of the serotonin transporter gene.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/10051007",
+ "title": "Age of onset in Huntington disease: sex specific influence of apolipoprotein E genotype and normal CAG repeat length.",
"type": "article-journal",
- "doi": "10.1016/j.pnpbp.2006.10.016",
+ "doi": "",
"authors": [
- ["Enrique", "Baca-Garcia"],
- ["Concepcion", "Vaquero-Lorenzo"],
- ["Montserrat", "Diaz-Hernandez"],
- ["Beatriz", "Rodriguez-Salgado"],
- ["Helen", "Dolengevich-Segal"],
- ["Manuel", "Arrojo-Romero"],
- ["Carlota", "Botillo-Martin"],
- ["Antonio", "Ceverino"],
- ["Jose Fernandez", "Piqueras"],
- ["M Mercedes", "Perez-Rodriguez"],
- ["Jeronimo", "Saiz-Ruiz"]
+ ["P", "Kehoe"],
+ ["M", "Krawczak"],
+ ["P S", "Harper"],
+ ["M J", "Owen"],
+ ["A L", "Jones"]
],
- "publisher": "Progress in neuro-psychopharmacology & biological psychiatry",
- "issn": "0278-5846",
- "date": "2006-12-13",
- "abstract": "Pharmacological studies indicate a dysregulation of the serotonergic system in obsessive-compulsive disorder (OCD). A variable number tandem repeats (VNTR) polymorphism with three alleles (Stin2.9, Stin2.10, Stin2.12) has been described in intron 2 of the serotonin transporter (5-HTT) gene. This polymorphism has been associated with unipolar depression, bipolar disorder, schizophrenia, and anxiety disorders including OCD.",
+ "publisher": "Journal of medical genetics",
+ "issn": "0022-2593",
+ "date": "1999-02-01",
+ "abstract": "Age of onset (AO) of Huntington disease (HD) is known to be correlated with the length of an expanded CAG repeat in the HD gene. Apolipoprotein E (APOE) genotype, in turn, is known to influence AO in Alzheimer disease, rendering the APOE gene a likely candidate to affect AO in other neurological diseases too. We therefore determined APOE genotype and normal CAG repeat length in the HD gene for 138 HD patients who were previously analysed with respect to CAG repeat length. Genotyping for APOE was performed blind to clinical information. In addition to highlighting the effect of the normal repeat length upon AO in maternally inherited HD and in male patients, we show that the APOE epsilon2epsilon3 genotype is associated with significantly earlier AO in males than in females. Such a sex difference in AO was not apparent for any of the other APOE genotypes. Our findings suggest that subtle differences in the course of the neurodegeneration in HD may allow interacting genes to exert gender specific effects upon AO.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17174018"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10051007"
},
{
- "id": "pmid:17115386",
+ "id": "pmid:10023115",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/17115386",
- "title": "Autopsy-proven Huntington's disease with 29 trinucleotide repeats.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/10023115",
+ "title": "Analysis of CAG repeat expansion in Huntington's disease gene (IT 15) in a Hungarian population.",
"type": "article-journal",
- "doi": "10.1002/mds.21195",
+ "doi": "10.1159/000008013",
"authors": [
- ["Christopher", "Kenney"],
- ["Suzanne", "Powell"],
- ["Joseph", "Jankovic"]
+ ["K", "Jakab"],
+ ["G", "G\u00e1rdi\u00e1n"],
+ ["E", "Endreffy"],
+ ["T", "Kalm\u00e1r"],
+ ["C", "Bachrati"],
+ ["L", "V\u00e9csei"],
+ ["I", "Rask\u00f3"]
],
- "publisher": "Movement disorders : official journal of the Movement Disorder Society",
- "issn": "0885-3185",
- "date": "2007-01-01",
- "abstract": "Huntington's disease (HD) is a neurodegenerative disorder associated with expansion of CAG trinucleotide repeats in the huntingtin gene. A minimum of 36 CAG repeats is usually reported in patients with clinical features of HD; 30 to 35 repeats represent an intermediate range. Here we report a 65-year-old male with autopsy-proven HD and 29 CAG repeats.",
+ "publisher": "European neurology",
+ "issn": "0014-3022",
+ "date": "1999-01-01",
+ "abstract": "Huntington's disease (HD) is a neurodegenerative disorder with autosomal dominant inheritance. The genetic defect is a CAG trinucleotide repeat expansion at the 5' end of the IT 15 gene on chromosome 4. This gene has not been analyzed in the Hungarian population yet. To obtain data DNA from 26 HD patients, 18 members of their families and 70 normal controls was amplified in the involved region by polymerase chain reaction. The CAG repeat numbers varied from 37 to 70 (median: 43) in HD patients and asymptomatic carriers, while individuals of the normal control group had 10-36 CAG repeat numbers (median: 18). The length of CAG repeat expansion in Hungarian HD patients was similar to that reported from other countries. The group of normal controls had the same CAG repeat expansion as populations reported from Western European countries. It is a useful piece of data for population genetics to prove that the population of Hungary is a m\u00e9lange of different nations that influenced the history of the country in the last 11 centuries. As opposed to this, the only closely related nation, the Finnish, was genetically more isolated during this time, so the frequency of HD (and also the number of CAG repeats in normal individuals) proved to be exceptionally low.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17115386"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10023115"
},
{
- "id": "pmid:17018562",
+ "id": "pmid:9949443",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/17018562",
- "title": "Replication of twelve association studies for Huntington's disease residual age of onset in large Venezuelan kindreds.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9949443",
+ "title": "Preimplantation diagnosis for Huntington's disease (HD): clinical application and analysis of the HD expansion in affected embryos.",
"type": "article-journal",
- "doi": "10.1136/jmg.2006.045153",
+ "doi": "10.1002/(sici)1097-0223(199812)18:13<1427::aid-pd493>3.0.co;2-3",
"authors": [
- ["J M", "Andresen"],
- ["J", "Gay\u00e1n"],
- ["S S", "Cherny"],
- ["D", "Brocklebank"],
- ["G", "Alkorta-Aranburu"],
- ["E A", "Addis"],
- ["L R", "Cardon"],
- ["D E", "Housman"],
- ["N S", "Wexler"]
+ ["K", "Sermon"],
+ ["V", "Goossens"],
+ ["S", "Seneca"],
+ ["W", "Lissens"],
+ ["A", "De Vos"],
+ ["M", "Vandervorst"],
+ ["A", "Van Steirteghem"],
+ ["I", "Liebaers"]
],
- "publisher": "Journal of medical genetics",
- "issn": "1468-6244",
- "date": "2006-10-03",
- "abstract": "The major determinant of age of onset in Huntington's disease is the length of the causative triplet CAG repeat. Significant variance remains, however, in residual age of onset even after repeat length is factored out. Many genetic polymorphisms have previously shown evidence of association with age of onset of Huntington's disease in several different populations.",
+ "publisher": "Prenatal diagnosis",
+ "issn": "0197-3851",
+ "date": "1998-12-01",
+ "abstract": "Huntington's disease (HD) is an autosomal dominant disease characterized by motor disturbance, cognitive loss and psychiatric manifestations, starting between the fourth and the fifth decade, followed by death within 10-20 years of onset of the disease. The disease-causing mutation is an expansion of a CAG triplet repeat at the 5' coding end of the Huntington gene. We have developed a single-cell PCR assay for the HD gene in order to propose preimplantation genetic diagnosis (PGD) for the couples at risk. We present here our first results with our first nine PGD cycles and also discuss the behaviour of the disease-causing expansion in pre-implantation embryos.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17018562"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9949443"
},
{
- "id": "pmid:17018277",
+ "id": "pmid:9818876",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/17018277",
- "title": "Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9818876",
+ "title": "Larger CAG expansions in skeletal muscle compared with lymphocytes in Kennedy disease but not in Huntington disease.",
"type": "article-journal",
- "doi": "10.1016/j.cell.2006.09.015",
+ "doi": "10.1212/wnl.51.5.1442",
"authors": [
- ["Libin", "Cui"],
- ["Hyunkyung", "Jeong"],
- ["Fran", "Borovecki"],
- ["Christopher N", "Parkhurst"],
- ["Naoko", "Tanese"],
- ["Dimitri", "Krainc"]
+ ["T", "Ansved"],
+ ["A", "Lundin"],
+ ["M", "Anvret"]
],
- "publisher": "Cell",
- "issn": "0092-8674",
- "date": "2006-10-06",
- "abstract": "Huntington's disease (HD) is an inherited neurodegenerative disease caused by a glutamine repeat expansion in huntingtin protein. Transcriptional deregulation and altered energy metabolism have been implicated in HD pathogenesis. We report here that mutant huntingtin causes disruption of mitochondrial function by inhibiting expression of PGC-1alpha, a transcriptional coactivator that regulates several metabolic processes, including mitochondrial biogenesis and respiration. Mutant huntingtin represses PGC-1alpha gene transcription by associating with the promoter and interfering with the CREB/TAF4-dependent transcriptional pathway critical for the regulation of PGC-1alpha gene expression. Crossbreeding of PGC-1alpha knockout (KO) mice with HD knockin (KI) mice leads to increased neurodegeneration of striatal neurons and motor abnormalities in the HD mice. Importantly, expression of PGC-1alpha partially reverses the toxic effects of mutant huntingtin in cultured striatal neurons. Moreover, lentiviral-mediated delivery of PGC-1alpha in the striatum provides neuroprotection in the transgenic HD mice. These studies suggest a key role for PGC-1alpha in the control of energy metabolism in the early stages of HD pathogenesis.",
+ "publisher": "Neurology",
+ "issn": "0028-3878",
+ "date": "1998-11-01",
+ "abstract": "The size of CAG repeats was compared in lymphocytes and skeletal muscle from nine patients with Huntington disease (HD) and two patients with Kennedy disease (KD). In HD, the number of CAG repeats did not differ between lymphocytes and skeletal muscle. In the two KD patients, however, the CAG expansion was larger in muscle than in lymphocytes. The difference in trinucleotide expansion between lymphocytes and muscle cells is not a universal phenomenon in trinucleotide repeat disorders, but seems to occur in disorders primarily affecting the neuromuscular system.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17018277"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9818876"
},
{
- "id": "pmid:16987871",
+ "id": "pmid:9806905",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/16987871",
- "title": "Cholinergic neuronal defect without cell loss in Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9806905",
+ "title": "Isolation and characterization of the rat huntingtin promoter.",
"type": "article-journal",
- "doi": "10.1093/hmg/ddl252",
+ "doi": "10.1042/bj3360227",
"authors": [
- ["Ruben", "Smith"],
- ["Hinfan", "Chung"],
- ["Sara", "Rundquist"],
- ["Marion L C", "Maat-Schieman"],
- ["Lesley", "Colgan"],
- ["Elisabet", "Englund"],
- ["Yong-Jian", "Liu"],
- ["Raymund A C", "Roos"],
- ["Richard L M", "Faull"],
- ["Patrik", "Brundin"],
- ["Jia-Yi", "Li"]
+ ["C", "Holzmann"],
+ ["W", "M\u00e4ueler"],
+ ["D", "Petersohn"],
+ ["T", "Schmidt"],
+ ["G", "Thiel"],
+ ["J T", "Epplen"],
+ ["O", "Riess"]
],
- "publisher": "Human molecular genetics",
- "issn": "0964-6906",
- "date": "2006-09-20",
- "abstract": "Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG-repeat expansion in the huntingtin (IT15) gene. The striatum is one of the regions most affected by neurodegeneration, resulting in the loss of the medium-sized spiny neurons. Traditionally, the large cholinergic striatal interneurons are believed to be spared. Recent studies demonstrate that neuronal dysfunction without cell death also plays an important role in early and mid-stages of the disease. Here, we report that cholinergic transmission is affected in a HD transgenic mouse model (R6/1) and in tissues from HD patients. Stereological analysis shows no loss of cholinergic neurons in the striatum or septum in R6/1 mice. In contrast, the levels of mRNA and protein for vesicular acetylcholine transporter (VAChT) and choline acetyltransferase (ChAT) are decreased in the striatum and cortex, and acetylcholine esterase activity is lowered in the striatum of R6/1 mice already at young ages. Accordingly, VAChT is also reduced in striatal tissue from patients with HD. The decrease of VAChT in the patient samples studied is restricted to the striatum and does not occur in the hippocampus or the spinal cord. The expression and localization of REST/NRSF, a transcriptional regulator for the VAChT and ChAT genes, are not altered in cholinergic neurons. We show that the R6/1 mice exhibit severe deficits in learning and reference memory. Taken together, our data show that the cholinergic system is dysfunctional in R6/1 and HD patients. Consequently, they provide a rationale for testing of pro-cholinergic drugs in this disease.",
+ "publisher": "The Biochemical journal",
+ "issn": "0264-6021",
+ "date": "1998-11-15",
+ "abstract": "Huntington's disease (HD) is a neurodegenerative disorder caused by a (CAG)>37 repeat expansion in a novel gene of unknown function. Although the huntingtin gene is expressed in neuronal and non-neuronal tissues, the disease affects nerve cells of selected regional areas of the central nervous system. To gain insight into the regulation of the HD gene we analysed 1348 bp of the rat huntingtin promoter region. This region lacks a TATA and a CAAT box, is rich in GC content and has several consensus sequences for binding sites for SP1, PEA3, Sif and H2A. The stretch between nucleotides -56 and -206 relative to the first ATG is highly conserved between human and rodents and it harbours several potential binding sites for transcription factors. We analysed deletion mutants fused with the chloramphenicol acetyltransferase reporter gene in transfected, HD-expressing neuronal (NS20Y, NG108-15) and non-neuronal Chinese hamster ovary cell lines. Hence these cells should contain the required trans-acting factors necessary for HD gene expression. Partial deletion of the evolutionarily conserved part of the promoter significantly decreases the activity in both neuronal and non-neuronal cells, indicating that the core promoter activity is located between nucleotides -332 and -15. DNase I footprinting and electrophoretic mobility-shift assays were used to define the nucleotide positions and binding affinity of DNA-protein interactions.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16987871"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9806905"
},
{
- "id": "pmid:16925544",
+ "id": "pmid:9792871",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/16925544",
- "title": "Juvenile Huntington disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9792871",
+ "title": "A Huntington disease-like neurodegenerative disorder maps to chromosome 20p.",
"type": "article-journal",
- "doi": "10.1111/j.1440-1754.2006.00921.x",
+ "doi": "10.1086/302093",
"authors": [
- ["Nimeshan", "Geevasinga"],
- ["Fiona H", "Richards"],
- ["Kristi J", "Jones"],
- ["Monique M", "Ryan"]
+ ["F", "Xiang"],
+ ["E W", "Almqvist"],
+ ["M", "Huq"],
+ ["A", "Lundin"],
+ ["M R", "Hayden"],
+ ["L", "Edstr\u00f6m"],
+ ["M", "Anvret"],
+ ["Z", "Zhang"]
],
- "publisher": "Journal of paediatrics and child health",
- "issn": "1034-4810",
- "date": "2006-09-01",
- "abstract": "Huntington disease (HD) is a dominantly inherited neurodegenerative disorder related to expansion of a triplet repeat sequence in the huntington gene on chromosome 4. Adult HD usually presents with chorea and personality changes. Juvenile HD is far less common and presents with parkinsonism, dystonia and seizures. We report a case of juvenile HD, showing extreme anticipation, in which diagnosis was delayed because of failure to recognise the significance of the family history and the characteristic clinical and radiologic features of this condition.",
+ "publisher": "American journal of human genetics",
+ "issn": "0002-9297",
+ "date": "1998-11-01",
+ "abstract": "Huntington disease (HD) is an autosomal dominant neurodegenerative disorder characterized by motor disturbance, cognitive loss, and psychiatric manifestations. The disease is associated with a CAG trinucleotide-repeat expansion in the Huntington gene (IT15) on chromosome 4p16.3. One family with a history of HD was referred to us initially for predictive testing using linkage analysis. However, the chromosome 4p region was completely excluded by polymorphic markers, and later no CAG-repeat expansion in the HD gene was detected. To map the disease trait segregating in this family, whole-genome screening with highly polymorphic dinucleotide-, trinucleotide-, and tetranucleotide-repeat DNA markers was performed. A positive LOD score of 3.01 was obtained for the marker D20S482 on chromosome 20p, by two-point LOD-score analysis with the MLINK program. Haplotype analysis indicated that the gene responsible for the disease is likely located in a 2.7-cM region between the markers D20S193 and D20S895. Candidate genes from the mapping region were screened for mutations.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16925544"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9792871"
},
{
- "id": "pmid:16918952",
+ "id": "pmid:9647305",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/16918952",
- "title": "The androgen receptor gene CAG repeat polymorphism does not predict increased risk of heart disease: longitudinal results from the Massachusetts Male Ageing Study.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9647305",
+ "title": "Genetic polymorphisms adjacent to the CAG repeat influence clinical features at onset in Huntington's disease.",
"type": "article-journal",
- "doi": "10.1111/j.1365-2265.2006.02598.x",
+ "doi": "10.1136/jnnp.64.6.758",
"authors": [
- ["Stephanie T", "Page"],
- ["Varant", "Kupelian"],
- ["William J", "Bremner"],
- ["John B", "McKinlay"]
+ ["I", "Vuillaume"],
+ ["P", "Vermersch"],
+ ["A", "Dest\u00e9e"],
+ ["H", "Petit"],
+ ["B", "Sablonni\u00e8re"]
],
- "publisher": "Clinical endocrinology",
- "issn": "0300-0664",
- "date": "2006-09-01",
- "abstract": "Sex steroids may contribute to the increased prevalence of heart disease (HD) in men compared to age-matched women. Androgens bind their cognate receptor, and androgen action is inversely proportional to the number of CAG repeats in exon 1 of the androgen receptor gene. Longer, less androgenic CAG repeats have been associated with higher high-density lipoprotein (HDL) levels, which might protect against HD. Therefore, we hypothesized that CAG repeat length contributes to HD risk in men.",
+ "publisher": "Journal of neurology, neurosurgery, and psychiatry",
+ "issn": "0022-3050",
+ "date": "1998-06-01",
+ "abstract": "To evaluate possible influences of CCG and delta2642 glutamic acid polymorphisms adjacent to the (CAG)n trinucleotide repeat in Huntington's disease gene IT15 on some clinical features (age and symptoms) at onset.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16918952"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9647305"
},
{
- "id": "pmid:16914060",
+ "id": "pmid:9611675",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/16914060",
- "title": "Genome-wide significance for a modifier of age at neurological onset in Huntington's disease at 6q23-24: the HD MAPS study.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9611675",
+ "title": "Serotonin transporter gene and risk for bipolar affective disorder: an association study in Spanish population.",
"type": "article-journal",
- "doi": "10.1186/1471-2350-7-71",
+ "doi": "10.1016/s0006-3223(97)00540-4",
"authors": [
- ["Jian-Liang", "Li"],
- ["Michael R", "Hayden"],
- ["Simon C", "Warby"],
- ["Alexandra", "Durr"],
- ["Patrick J", "Morrison"],
- ["Martha", "Nance"],
- ["Christopher A", "Ross"],
- ["Russell L", "Margolis"],
- ["Adam", "Rosenblatt"],
- ["Ferdinando", "Squitieri"],
- ["Luigi", "Frati"],
- ["Estrella", "G\u00f3mez-Tortosa"],
- ["Carmen Ayuso", "Garc\u00eda"],
- ["Oksana", "Suchowersky"],
- ["Mary Lou", "Klimek"],
- ["Ronald J A", "Trent"],
- ["Elizabeth", "McCusker"],
- ["Andrea", "Novelletto"],
- ["Marina", "Frontali"],
- ["Jane S", "Paulsen"],
- ["Randi", "Jones"],
- ["Tetsuo", "Ashizawa"],
- ["Alice", "Lazzarini"],
- ["Vanessa C", "Wheeler"],
- ["Ranjana", "Prakash"],
- ["Gang", "Xu"],
- ["Luc", "Djouss\u00e9"],
- ["Jayalakshmi Srinidhi", "Mysore"],
- ["Tammy", "Gillis"],
- ["Michael", "Hakky"],
- ["L Adrienne", "Cupples"],
- ["Marie H", "Saint-Hilaire"],
- ["Jang-Ho J", "Cha"],
- ["Steven M", "Hersch"],
- ["John B", "Penney"],
- ["Madaline B", "Harrison"],
- ["Susan L", "Perlman"],
- ["Andrea", "Zanko"],
- ["Ruth K", "Abramson"],
- ["Anthony J", "Lechich"],
- ["Ayana", "Duckett"],
- ["Karen", "Marder"],
- ["P Michael", "Conneally"],
- ["James F", "Gusella"],
- ["Marcy E", "MacDonald"],
- ["Richard H", "Myers"]
+ ["B", "Guti\u00e9rrez"],
+ ["M J", "Arranz"],
+ ["D A", "Collier"],
+ ["V", "Vall\u00e8s"],
+ ["R", "Guillamat"],
+ ["J", "Bertranpetit"],
+ ["R M", "Murray"],
+ ["L", "F\u00e3n\u00e1s"]
],
- "publisher": "BMC medical genetics",
- "issn": "1471-2350",
- "date": "2006-08-17",
- "abstract": "Age at onset of Huntington's disease (HD) is correlated with the size of the abnormal CAG repeat expansion in the HD gene; however, several studies have indicated that other genetic factors also contribute to the variability in HD age at onset. To identify modifier genes, we recently reported a whole-genome scan in a sample of 629 affected sibling pairs from 295 pedigrees, in which six genomic regions provided suggestive evidence for quantitative trait loci (QTL), modifying age at onset in HD.",
+ "publisher": "Biological psychiatry",
+ "issn": "0006-3223",
+ "date": "1998-06-01",
+ "abstract": "The serotonin transporter (5-HTT) is an important candidate gene for the genetic transmission of manic depressive illness. Many studies of patients with affective disorders have found abnormalities in serotonin metabolism and dysregulation of the transporter itself. In the present study, we hypothesize that genetic variation in the 5-HTT gene (17q11.1-17q12) may have an effect in the etiology of manic depression.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16914060"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9611675"
},
{
- "id": "pmid:16690085",
+ "id": "pmid:9536080",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/16690085",
- "title": "Association between serotonin transporter gene and borderline personality disorder.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9536080",
+ "title": "Aggregation of N-terminal huntingtin is dependent on the length of its glutamine repeats.",
"type": "article-journal",
- "doi": "10.1016/j.jpsychires.2006.03.010",
+ "doi": "10.1093/hmg/7.5.777",
"authors": [
- ["Xingqun", "Ni"],
- ["Kirsten", "Chan"],
- ["Natalie", "Bulgin"],
- ["Tricia", "Sicard"],
- ["Ramprasad", "Bismil"],
- ["Shelley", "McMain"],
- ["James L", "Kennedy"]
+ ["S H", "Li"],
+ ["X J", "Li"]
],
- "publisher": "Journal of psychiatric research",
- "issn": "0022-3956",
- "date": "2006-05-11",
- "abstract": "Borderline personality disorder (BPD) is characterized by a pervasive pattern of instability in regulation of emotion, interpersonal relationships, self-image, and impulse control beginning in early adulthood. BPD affects about 1-2% of the general population and has a high mortality rate as a result of suicide and impulsive behaviour. The serotonin transporter gene (5-HTT) is considered as a candidate gene for BPD as multiple lines of evidence have suggested that it plays an important role in suicide, impulsive behaviour, and emotional liability. To test for an association between 5-HTT and BPD, we genotyped three common polymorphisms: the serotonin transporter linked promoter region (5-HTTLPR); a variable number of tandem repeat (VNTR) in intron 2, and a single nucleotide variant (A/G) within the LPR region. Eighty-nine Caucasian patients with BPD and 269 Caucasian healthy controls were analyzed. The program UNPHASED was used to compare allele and haplotype frequencies between cases and controls. Significant differences in allele frequencies of the VNTR marker (p=0.012) and haplotype frequencies (p=0.002) between patients and controls were found. Compared with healthy controls, patients with BPD showed higher frequencies of the 10 repeat of the VNTR marker and the S-10 haplotype, and lower 12 repeat and L(A)-12 haplotype. Our results suggest that the serotonin transporter gene may play a role in the aetiology of borderline personality disorder.",
+ "publisher": "Human molecular genetics",
+ "issn": "0964-6906",
+ "date": "1998-05-01",
+ "abstract": "Huntington's disease (HD) is caused by expansion of a glutamine repeat in huntingtin. Mutant huntingtin contains 36-55 repeats in adult HD patients and >60 repeats in juvenile HD patients. An N-terminal fragment of mutant huntingtin forms aggregates in neuronal nuclei in the brains of transgenic mice and HD patients. Aggregation of expanded polyglutamine is thought to be a common pathological mechanism in HD and other glutamine repeat diseases. It is not clear how the length of the repeats is correlated with formation of protein aggregates. By expressing a series of huntingtin constructs encoding various glutamine repeats (23-150 units) in cultured cells we observed N-terminal fragments of huntingtin (amino acids 1-67 and 1-212), but not full-length huntingtins, with glutamine repeats >/=66 units formed protein aggregates. Huntingtin aggregation was not induced when the repeat was /=120 units. This study suggests that various N-terminal fragments of mutant huntingtin can form aggregates and that aggregation is prompted by lengthening the glutamine repeat.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16690085"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9536080"
},
{
- "id": "pmid:16687439",
+ "id": "pmid:9595987",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/16687439",
- "title": "Genetic background modifies nuclear mutant huntingtin accumulation and HD CAG repeat instability in Huntington's disease knock-in mice.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9595987",
+ "title": "1H NMR spectroscopy studies of Huntington's disease: correlations with CAG repeat numbers.",
"type": "article-journal",
- "doi": "10.1093/hmg/ddl125",
+ "doi": "10.1212/wnl.50.5.1357",
"authors": [
- ["Alejandro", "Lloret"],
- ["Ella", "Dragileva"],
- ["Allison", "Teed"],
- ["Janice", "Espinola"],
- ["Elisa", "Fossale"],
- ["Tammy", "Gillis"],
- ["Edith", "Lopez"],
- ["Richard H", "Myers"],
- ["Marcy E", "MacDonald"],
- ["Vanessa C", "Wheeler"]
+ ["B G", "Jenkins"],
+ ["H D", "Rosas"],
+ ["Y C", "Chen"],
+ ["T", "Makabe"],
+ ["R", "Myers"],
+ ["M", "MacDonald"],
+ ["B R", "Rosen"],
+ ["M F", "Beal"],
+ ["W J", "Koroshetz"]
],
- "publisher": "Human molecular genetics",
- "issn": "0964-6906",
- "date": "2006-05-10",
- "abstract": "Genetically precise models of Huntington's disease (HD), Hdh CAG knock-in mice, are powerful systems in which phenotypes associated with expanded HD CAG repeats are studied. To dissect the genetic pathways that underlie such phenotypes, we have generated Hdh(Q111) knock-in mouse lines that are congenic for C57BL/6, FVB/N and 129Sv inbred genetic backgrounds and investigated four Hdh(Q111) phenotypes in these three genetic backgrounds: the intergenerational instability of the HD CAG repeat and the striatal-specific somatic HD CAG repeat expansion, nuclear mutant huntingtin accumulation and intranuclear inclusion formation. Our results reveal increased intergenerational and somatic instability of the HD CAG repeat in C57BL/6 and FVB/N backgrounds compared with the 129Sv background. The accumulation of nuclear mutant huntingtin and the formation of intranuclear inclusions were fastest in the C57BL/6 background, slowest in the 129Sv background and intermediate in the FVB/N background. Inbred strain-specific differences were independent of constitutive HD CAG repeat size and did not correlate with Hdh mRNA levels. These data provide evidence for genetic modifiers of both intergenerational HD CAG repeat instability and striatal-specific phenotypes. Different relative contributions of C57BL/6 and 129Sv genetic backgrounds to the onset of nuclear mutant huntingtin and somatic HD CAG repeat expansion predict that the initiation of each of these two phenotypes is modified by different genes. Our findings set the stage for defining disease-related genetic pathways that will ultimately provide insight into disease mechanism.",
+ "publisher": "Neurology",
+ "issn": "0028-3878",
+ "date": "1998-05-01",
+ "abstract": "Huntington's disease (HD) is the result of an expanded (CAG) repeat in a gene on chromosome 4. A consequence of the gene defect may be progressive impairment of energy metabolism. We previously showed increased occipital cortex lactate in HD using localized 1H spectroscopy. We have now extended these studies to show an almost threefold elevation in occipital cortex lactate in 31 HD patients as compared with 17 normal control subjects (p < 10(-11)). The spectra in three presymptomatic gene-positive patients were identical to normal control subjects in cortical regions, but three in eight showed elevated lactate in the striatum. Similar to recently reported increases in task-related activation of the striatum in the dominant hemisphere, we found that striatal lactate levels in HD patients were markedly asymmetric (higher on the left side). Markers of neuronal degeneration, decreased N-acetylaspartate (NAA)/creatine and increased choline/creatine levels, were symmetric. Both decreased NAA and increased lactate in the striatum significantly correlated with duration of symptoms. When divided by his or her age, an individual's striatal NAA loss and lactate increase were found to directly correlate with the subject's CAG repeat number, with correlation coefficients of 0.8 and 0.7, respectively. Similar correlations were noted between postmortem cell loss and age versus CAG repeat length. Together, these data provide further evidence for an interaction between neuronal activation and a defect in energy metabolism in HD that may extend to presymptomatic subjects.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16687439"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9595987"
},
{
- "id": "pmid:16626669",
+ "id": "pmid:9577843",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/16626669",
- "title": "DNA microarray analysis of striatal gene expression in symptomatic transgenic Huntington's mice (R6/2) reveals neuroinflammation and insulin associations.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9577843",
+ "title": "Role of serotonin transporter promoter repeat length polymorphism (5-HTTLPR) in seasonality and seasonal affective disorder.",
"type": "article-journal",
- "doi": "10.1016/j.brainres.2006.02.102",
+ "doi": "10.1038/sj.mp.4000360",
"authors": [
- ["Susan F", "Crocker"],
- ["Willard J", "Costain"],
- ["Harold A", "Robertson"]
+ ["N E", "Rosenthal"],
+ ["C M", "Mazzanti"],
+ ["R L", "Barnett"],
+ ["T A", "Hardin"],
+ ["E H", "Turner"],
+ ["G K", "Lam"],
+ ["N", "Ozaki"],
+ ["D", "Goldman"]
],
- "publisher": "Brain research",
- "issn": "0006-8993",
- "date": "2006-04-19",
- "abstract": "Huntington's disease (HD) is an inherited, progressive neurodegenerative disorder caused by CAG repeat expansion in the gene that codes for the protein huntingtin. The underlying neuropathological events leading to the selectivity of striatal neuronal loss are unknown. However, the huntingtin mutation interferes at several levels of normal cell function. The complexity of this disease makes microarray analysis an appealing technique to begin the identification of common pathways that may contribute to the pathology. In this study, striatal tissue was extracted for gene expression profiling from wild-type and symptomatic transgenic Huntington mice (R6/2) expressing part of the human Huntington's disease gene. We interrogated a 15 K high-density mouse EST array not previously used for HD and identified 170 significantly differentially expressed ESTs in symptomatic R6/2 mice. Of the 80 genes with known function, 9 genes had previously been identified as altered in HD. 71 known genes were associated with HD for the first time. The data obtained from this study confirm and extend previous observations using DNA microarray techniques on genetic models for HD, revealing novel changes in expression in a number of genes not previously associated with HD. Further bioinformatic analysis, using software to construct biological association maps, focused attention on proteins such as insulin and TH1-mediated cytokines, suggesting that they may be important regulators of affected genes. These results may provide insight into the regulation and interaction of genes that contribute to adaptive and pathological processes involved in HD.",
+ "publisher": "Molecular psychiatry",
+ "issn": "1359-4184",
+ "date": "1998-03-01",
+ "abstract": "Seasonal variations in mood and behavior (seasonality) and seasonal affective disorder (SAD) have been attributed to seasonal fluctuations in brain serotonin (5-HT). the short (s), as opposed to the long (l), allele of the 5-HT transporter linked polymorphism (5-HTTLPR) has been associated with neuroticism and depression. We hypothesized that this short allele would also be associated with SAD and with higher levels of seasonality. Ninety-seven SAD patients and 71 non-seasonal healthy controls with low seasonality levels were genotyped for 5-HTTLPR and compared statistically. Patients with SAD were less likely to have the l/l genotype (27.8% vs 47.9%; P < 0.01) and more likely to have the s allele (44.8% vs 32.4%; P < 0.02) as compared to controls. The three 5-HTTLPR genotypes were also differentially distributed in patients and controls (P < 0.03). The SAD patients with the l/l genotype had a lower mean seasonality score than did patients with the other two genotypes (mean +/- s.d. = 15.3 +/- 2.8 vs 17.1 +/- 3.4 respectively; P < 0.02). The 5-HTTLPR short allele contributes to the trait of seasonality and is a risk factor for SAD, providing further evidence for a relationship between genetic variation in the 5-HT transporter (5-HTT) and behavior.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16626669"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9577843"
},
{
- "id": "pmid:16564426",
+ "id": "pmid:9485067",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/16564426",
- "title": "Normal sensitivity to excitotoxicity in a transgenic Huntington's disease rat.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9485067",
+ "title": "[11C]raclopride-PET studies of the Huntington's disease rate of progression: relevance of the trinucleotide repeat length.",
"type": "article-journal",
- "doi": "10.1016/j.brainresbull.2006.01.003",
+ "doi": "10.1002/ana.410430216",
"authors": [
- ["C", "Winkler"],
- ["J M A C", "Gil"],
- ["I M", "Ara\u00fajo"],
- ["O", "Riess"],
- ["T", "Skripuletz"],
- ["S", "von H\u00f6rsten"],
- ["A", "Peters\u00e9n"]
+ ["A", "Antonini"],
+ ["K L", "Leenders"],
+ ["D", "Eidelberg"]
],
- "publisher": "Brain research bulletin",
- "issn": "0361-9230",
- "date": "2006-01-20",
- "abstract": "Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by a CAG repeat expansion in the HD gene. Excitotoxic cell damage by excessive stimulation of glutamate receptors has been hypothesized to contribute to the pathogenesis of HD. Transgenic mouse models of HD have shown variable sensitivity to excitotoxicity. The models differ in the genetic background, the type and length of the promoter driving the transgene expression, the CAG repeat length and/or the HD gene construct length. Furthermore, one has to differentiate whether transgenic or knock-in models have been used. All these factors may be involved in determining the responsiveness to an excitotoxic insult. Here, we explored the responsiveness to excitotoxic damage using a transgenic HD rat model carrying 22% of the rat HD gene which is driven by the rat HD promoter and which harbors 51 CAG repeats. 3 and 18 months old transgenic HD rats and their wild-type littermates received unilateral intrastriatal injections of the glutamate analogue quinolinic acid. Lesion size was assessed 7 days later using the degenerative stain Fluoro-Jade and by immunohistochemistry for the neuronal protein NeuN. No difference in susceptibility to excitotoxicity was found between the groups. Our study supports mouse data showing maintained susceptibility to excitotoxicity with the expression of around 25% of the full HD gene. Differences in sensitivity to excitotoxicity between genetic animal models of HD may be dependent on the length of the expressed HD gene although additional factors are also likely to be important.",
+ "publisher": "Annals of neurology",
+ "issn": "0364-5134",
+ "date": "1998-02-01",
+ "abstract": "We used [11C]raclopride and positron emission tomography (PET) to assess the relationship between striatal dopamine D2 receptor binding, trinucleotide repeat number (CAG), and subject age in 10 asymptomatic and 8 symptomatic carriers of the Huntington's disease (HD) mutation. In both preclinical and symptomatic gene carriers, we found significant correlations between CAG repeat length and the ratio of percent loss in striatal D2 receptor binding divided by age. In accord with neuropathological studies, we obtained an intercept at 35.5 CAG repeats in the symptomatic HD patients. Nonetheless, we noted that the slopes of the correlation lines differed significantly for the presymptomatic and symptomatic cohorts. These PET results support the notion that the HD disease process is a function of trinucleotide length and age, and that the development of clinical signs and symptoms is associated with CAG repeat lengths greater than 35.5. However, our analysis also suggests that striatal degeneration may proceed in a nonlinear fashion. These findings have implications for the design of neuroprotective strategies for the treatment of HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16564426"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9485067"
},
{
- "id": "pmid:16526033",
+ "id": "pmid:9462548",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/16526033",
- "title": "Intergeneration CAG expansion and contraction in a Chinese HD family.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9462548",
+ "title": "Instability of dinucleotide repeats in Hodgkin's disease.",
"type": "article-journal",
- "doi": "10.1002/ajmg.b.30261",
+ "doi": "10.1002/(sici)1096-8652(199802)57:2<148::aid-ajh10>3.0.co;2-8",
"authors": [
- ["Yanping", "Tang"],
- ["Ying", "Wang"],
- ["Ping", "Yang"],
- ["Yuan", "Liu"],
- ["Bo", "Wang"],
- ["Robert", "Podolsky"],
- ["Richard", "McIndoe"],
- ["Cong-Yi", "Wang"]
+ ["Z", "Mark"],
+ ["A", "Toren"],
+ ["N", "Amariglio"],
+ ["G", "Schiby"],
+ ["F", "Brok-Simoni"],
+ ["G", "Rechavi"]
],
- "publisher": "American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics",
- "issn": "1552-4841",
- "date": "2006-04-05",
- "abstract": "The prevalence of juvenile-onset Huntington's disease (HD) is about ten times lower than adult HD. Here we report a Chinese HD family showing both intergeneration CAG expansion and contraction. The expansion resulted from a paternal transmission which leads to juvenile-onset HD for a 17-year-old Chinese boy (III-5). More interestingly, a contraction was noticed in a maternal transmission (III-3), which changed the CAG repeat from an expanded, disease-causing allele (48 repeats) to a normal or intermediate allele (34 repeats). Of note, the contraction resulted in a deletion of 14 CAG repeats, which is much larger than previously reported contractions. Our results are consistent with previous observations in Western Caucasians that juvenile-onset HD is more likely inherited through the male germline.",
+ "publisher": "American journal of hematology",
+ "issn": "0361-8609",
+ "date": "1998-02-01",
+ "abstract": "Tumorigenesis has been shown to proceed through a series of genetic alterations involving protooncogenes and tumor suppressor genes. However, the investigation of genomic instability of microsatellites has disclosed a new mechanism for human carcinogenesis, which is involved not only in hereditary nonpolyposis colon cancer (HNPCC) but in a number of other malignancies as well. To determine whether microsatellite instability is involved in Hodgkin's disease, we screened 16 such tumors using 7 microsatellite marker loci on 6 chromosome arms 4, 5, 9p, 9q, 11, 14, and 17. Using the polymerase chain reaction method, DNA samples from the tumors and from normal peripheral blood leukocytes from each patient were compared for the allelic pattern produced at each locus. Five cases of genomic instability were identified, suggesting that this mechanism is relevant to the pathogenesis of HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16526033"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9462548"
},
{
- "id": "pmid:16515395",
+ "id": "pmid:23604331",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/16515395",
- "title": "Serotonin transporter polymorphisms and side effects in antidepressant therapy--a pilot study.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23604331",
+ "title": "Inhibition of \u03b1-ketoglutarate-and pyruvate dehydrogenase complexes in E. coli by a glutathione S-transferase containing a pathological length poly-Q domain: A possible role of energy deficit in neurological diseases associated with poly-Q expansions?",
"type": "article-journal",
- "doi": "10.2217/14622416.7.2.159",
+ "doi": "10.1007/s11357-998-0004-x",
"authors": [
- ["Johannes", "Popp"],
- ["Stefan", "Leucht"],
- ["Stephan", "Heres"],
- ["Werner", "Steimer"]
+ ["A J", "Cooper"],
+ ["K F", "Sheu"],
+ ["J R", "Burke"],
+ ["O", "Onodera"],
+ ["W J", "Strittmatter"],
+ ["A D", "Roses"],
+ ["J P", "Blass"]
],
- "publisher": "Pharmacogenomics",
- "issn": "1462-2416",
- "date": "2006-03-01",
- "abstract": "To assess the influence of the serotonin transporter variable number of tandem repeat (HTT-VNTR) polymorphism and the serotonin transporter-gene-linked polymorphic region (HTTLPR) polymorphism on development of side effects under antidepressant therapy.",
+ "publisher": "Age",
+ "issn": "",
+ "date": "1998-01-01",
+ "abstract": "At least seven adult-onset neurodegenerative diseases, including Huntington's disease (HD), are caused by genes containing expanded CAG triplets within their coding regions. The expanded CAG repeats give rise to extended stretches of polyglutamines (Qn) in the proteins expressed by the affected genes. Generally, n \u226540 in affected individuals and \u226436 in clinically unaffected individuals. The expansion has been proposed to confer a \"toxic gain of function\" to the mutated protein. Poly-Q domains have recently been shown to be excellent substrates of tissue transglutaminase. We investigated the effects of expression of glutathione S-transferase constructs containing poly-Q inserts of various lengths (GSTQn where n = 0, 10, 62 or 81) on the activity of some key metabolic enzymes in the host Escherischia coil-an organism not known to have transglutaminase activity. E. coil carrying the GSTQ62 construct exhibited statistically significant decreases in the specific activities of \u03b1-ketoglutarate dehydrogenase complex (KGDHC) and pyruvate dehydrogenase complex (PDHC). Previous work has shown that KGDHC and PDHC activities are reduced in the brains of Alzheimer's disease (AD) patients. Our results suggest that KGDHC and PDHC may be particularly susceptible to the effects of a number of disparate insults, including those associated with AD and HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16515395"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23604331"
},
{
- "id": "pmid:16321399",
+ "id": "pmid:9299885",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/16321399",
- "title": "Oligoproline effects on polyglutamine conformation and aggregation.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9299885",
+ "title": "Analysis of the (CAG)n repeat at the IT15 locus in a population from Calabria (southern Italy).",
"type": "article-journal",
- "doi": "10.1016/j.jmb.2005.10.053",
+ "doi": "",
"authors": [
- ["Anusri", "Bhattacharyya"],
- ["Ashwani K", "Thakur"],
- ["Veronique M", "Chellgren"],
- ["Geetha", "Thiagarajan"],
- ["Angela D", "Williams"],
- ["Brian W", "Chellgren"],
- ["Trevor P", "Creamer"],
- ["Ronald", "Wetzel"]
+ ["O", "Leone"],
+ ["M", "Muglia"],
+ ["A L", "Gabriele"],
+ ["G", "Annesi"],
+ ["F L", "Conforti"],
+ ["E", "Imbrogno"],
+ ["L", "Imbrogno"],
+ ["C", "Brancati"]
],
- "publisher": "Journal of molecular biology",
- "issn": "0022-2836",
- "date": "2005-11-09",
- "abstract": "There are nine known expanded CAG repeat neurological diseases, including Huntington's disease (HD), each involving the repeat expansion of polyglutamine (polyGln) in a different protein. Similar conditions can be induced in animal models by expression of the polyGln sequence alone or in other protein contexts. Besides the polyGln sequence, the cellular context of the disease protein, and the sequence context of the polyGln within the disease protein, are both likely to contribute to polyGln physical behavior and to pathology. In HD, the N-terminal, exon-1 segment of the protein huntingtin contains the polyGln sequence immediately followed by an oligoproline region. We show here that introduction of a P10 sequence C-terminal to polyGln in synthetic peptides decreases both the rate of formation and the apparent stability of the amyloid-like aggregates associated with this family of diseases. The sequence can be trimmed to P6 without altering the suppression, but a P3 sequence is ineffective. Spacers up to at least three amino acid residues in length can be inserted between polyGln and P10 without altering this effect. There is no suppression, however, when the P10 sequence is either placed on the N-terminal side of polyGln or attached to polyGln via a side-chain tether. The nucleation mechanism of a Q40 sequence is unchanged upon addition of a P10 C-terminal extension, yielding a critical nucleus of one. The effects of oligoPro length and structural context on polyGln aggregation are correlated strongly with alterations in the circular dichroism spectra of the monomeric peptides. For example, the P10 sequence eliminates the small amount of alpha helical content otherwise exhibited by the Q40 sequence. The P10 sequence may suppress aggregation by stabilizing an aggregation-incompetent conformation of the monomer. The effect is transportable: a P10 sequence fixed to the C terminus of the sequence Abeta similarly modulates amyloid fibril formation.",
+ "publisher": "Human biology",
+ "issn": "0018-7143",
+ "date": "1997-10-01",
+ "abstract": "The defect causing Huntington's disease (HD) has recently been discovered as an expanded CAG trinucleotide repeat located at the 5' end of the IT15 gene. This discovery allows the molecular diagnosis of HD by measuring the CAG repeat length. The normal and pathological repeat ranges in a population need to be established before a diagnostic test for HD can be performed. To determine the distribution of IT15 alleles in a population from Calabria (southern Italy), we analyzed 102 normal subjects and 9 HD patients coming from a defined area of Calabria (province of Cosenza). Expanded alleles ranged from 44 to 76 repeats. Normal alleles varied from 8 to 27 repeats, which is one of the lowest values observed at the top of the normal range; the mean was significantly different from the value observed in six other populations. The allele distribution seemed to group mainly around the mode, and no intermediate alleles were present in our sample. These results suggest a particular stability of the CAG repeat at the IT15 locus in the Calabrian group and confirm once again the peculiar genetic structure of this population.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16321399"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9299885"
},
{
- "id": "pmid:16261565",
+ "id": "pmid:9267034",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/16261565",
- "title": "Preclinical Huntington's disease: compensatory brain responses during learning.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9267034",
+ "title": "Huntingtin-encoded polyglutamine expansions form amyloid-like protein aggregates in vitro and in vivo.",
"type": "article-journal",
- "doi": "10.1002/ana.20684",
+ "doi": "10.1016/s0092-8674(00)80514-0",
"authors": [
- ["Andrew", "Feigin"],
- ["Maria-Felice", "Ghilardi"],
- ["Chaorui", "Huang"],
- ["Yilong", "Ma"],
- ["Maren", "Carbon"],
- ["Mark", "Guttman"],
- ["Jane S", "Paulsen"],
- ["Claude P", "Ghez"],
- ["David", "Eidelberg"]
+ ["E", "Scherzinger"],
+ ["R", "Lurz"],
+ ["M", "Turmaine"],
+ ["L", "Mangiarini"],
+ ["B", "Hollenbach"],
+ ["R", "Hasenbank"],
+ ["G P", "Bates"],
+ ["S W", "Davies"],
+ ["H", "Lehrach"],
+ ["E E", "Wanker"]
],
- "publisher": "Annals of neurology",
- "issn": "0364-5134",
- "date": "2006-01-01",
- "abstract": "Motor sequence learning is abnormal in presymptomatic Huntington's disease (p-HD). The neural substrates underlying this early manifestation of HD are poorly understood. To study the mechanism of this cognitive abnormality in p-HD, we used positron emission tomography to record brain activity during motor sequence learning in these subjects. Eleven p-HD subjects (age, 45.8 +/- 11.0 years; CAG repeat length, 41.6 +/- 1.8) and 11 age-matched control subjects (age, 45.3 +/- 13.4 years) underwent H(2) (15)O positron emission tomography while performing a set of kinematically controlled motor sequence learning and execution tasks. Differences in regional brain activation responses between groups and conditions were assessed. In addition, we identified discrete regions in which learning-related activity correlated with performance. We found that sequence learning was impaired in p-HD subjects despite normal motor performance. In p-HD, activation responses during learning were abnormally increased in the left mediodorsal thalamus and orbitofrontal cortex (OFC; BA 11/47). Impaired learning performance in these subjects was associated with increased activation responses in the precuneus (BA 18/31). These data suggest that enhanced activation of thalamocortical pathways during motor learning can compensate for caudate degeneration in p-HD. Nonetheless, this mechanism may not be sufficient to sustain a normal level of task performance, even during the presymptomatic stage of the disease.",
+ "publisher": "Cell",
+ "issn": "0092-8674",
+ "date": "1997-08-08",
+ "abstract": "The mechanism by which an elongated polyglutamine sequence causes neurodegeneration in Huntington's disease (HD) is unknown. In this study, we show that the proteolytic cleavage of a GST-huntingtin fusion protein leads to the formation of insoluble high molecular weight protein aggregates only when the polyglutamine expansion is in the pathogenic range. Electron micrographs of these aggregates revealed a fibrillar or ribbon-like morphology, reminiscent of scrapie prions and beta-amyloid fibrils in Alzheimer's disease. Subcellular fractionation and ultrastructural techniques showed the in vivo presence of these structures in the brains of mice transgenic for the HD mutation. Our in vitro model will aid in an eventual understanding of the molecular pathology of HD and the development of preventative strategies.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16261565"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9267034"
},
{
- "id": "pmid:16221531",
+ "id": "pmid:9150168",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/16221531",
- "title": "The platelet maximum number of A2A-receptor binding sites (Bmax) linearly correlates with age at onset and CAG repeat expansion in Huntington's disease patients with predominant chorea.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9150168",
+ "title": "The likelihood of being affected with Huntington disease by a particular age, for a specific CAG size.",
"type": "article-journal",
- "doi": "10.1016/j.neulet.2005.09.037",
+ "doi": "",
"authors": [
- ["Vittorio", "Maglione"],
- ["Milena", "Cannella"],
- ["Tiziana", "Martino"],
- ["Antonio", "De Blasi"],
- ["Luigi", "Frati"],
- ["Ferdinando", "Squitieri"]
+ ["R R", "Brinkman"],
+ ["M M", "Mezei"],
+ ["J", "Theilmann"],
+ ["E", "Almqvist"],
+ ["M R", "Hayden"]
],
- "publisher": "Neuroscience letters",
- "issn": "0304-3940",
- "date": "2005-10-10",
- "abstract": "Huntington's disease (HD) is caused by an expanded CAG mutation and may show a heterogeneous clinical presentation. To date, although the age at onset mostly depends on the expanded CAG repeat number, no validated easy-to-test biomarkers exist either for following up patients progression rate or for exactly predicting age at onset (defined as the time when motor clinical manifestations first became noticeable). We tested the function of A(2A) receptor, strongly expressed in the brain striatum and peripheral cells, in patients' blood platelets and confirmed a maximum number of binding sites (B(max)) higher than in controls (216 +/- 9 versus 137 +/- 7; p=0.0001). We found a linear correlation between the receptor B(max) and the expanded CAG repeat number (n=52, r(2)=0.19, p=0.0011). When we selected the patients according to their clinical presentation (according to the predominating motor manifestations) and plotted the receptor B(max) against patients' age at onset, we found a significant linear correlation only when considering those subjects with chorea predominant on all other motor symptoms (n=26, r(2)=0.39, p=0.0007). Because the typical chorea may depend on early dysfunction of the striatum in HD, peripheral A(2A) amplification in blood platelets might reflect a central dysfunction in this part of the brain. Further studies on a larger sample size should confirm whether the analysis of A(2A)-receptor binding in patients' blood could be a useful clinical marker according to the patients' phenotype.",
+ "publisher": "American journal of human genetics",
+ "issn": "0002-9297",
+ "date": "1997-05-01",
+ "abstract": "Prior studies describing the relationship between CAG size and the age at onset of Huntington disease (HD) have focused on affected persons. To further define the relationship between CAG repeat size and age at onset of HD, we now have analyzed a large cohort of affected and asymptomatic at-risk persons with CAG expansion. This cohort numbered 1,049 persons, including 321 at-risk and 728 affected individuals with a CAG size of 29-121 repeats. Kaplan-Meier analysis has provided curves for determining the likelihood of onset at a given age, for each CAG repeat length in the 39-50 range. The curves were significantly different (P < .0005), with relatively narrow 95% confidence intervals (95% CI) (+/-10%). Penetrance of the mutation for HD also was examined. Although complete penetrance of HD was observed for CAG sizes of > or = 42, only a proportion of those with a CAG repeat length of 36-41 showed signs or symptoms of HD within a normal life span. These data provide information concerning the likelihood of being affected, by a specific age, with a particular CAG size, and they may be useful in predictive-testing programs and for the design of clinical trials for persons at increased risk for HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16221531"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9150168"
},
{
- "id": "pmid:16111888",
+ "id": "pmid:9108071",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/16111888",
- "title": "Evaluation of the benzothiazole aggregation inhibitors riluzole and PGL-135 as therapeutics for Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9108071",
+ "title": "Genotypes at the GluR6 kainate receptor locus are associated with variation in the age of onset of Huntington disease.",
"type": "article-journal",
- "doi": "10.1016/j.nbd.2005.07.007",
+ "doi": "10.1073/pnas.94.8.3872",
"authors": [
- ["Emma", "Hockly"],
- ["Jamie", "Tse"],
- ["Amy L", "Barker"],
- ["Donna L", "Moolman"],
- ["Jean-Luc", "Beunard"],
- ["Adrian P", "Revington"],
- ["Kim", "Holt"],
- ["Sunny", "Sunshine"],
- ["Hilary", "Moffitt"],
- ["Kirupa", "Sathasivam"],
- ["Benjamin", "Woodman"],
- ["Erich E", "Wanker"],
- ["Philip A S", "Lowden"],
- ["Gillian P", "Bates"]
+ ["D C", "Rubinsztein"],
+ ["J", "Leggo"],
+ ["M", "Chiano"],
+ ["A", "Dodge"],
+ ["G", "Norbury"],
+ ["E", "Rosser"],
+ ["D", "Craufurd"]
],
- "publisher": "Neurobiology of disease",
- "issn": "0969-9961",
- "date": "2005-08-18",
- "abstract": "Huntington's disease (HD) is an inherited progressive neurological disorder for which there is no effective therapy. It is caused by a CAG/polyglutamine repeat expansion that leads to abnormal protein aggregation and deposition in the brain. Several compounds have been shown to disrupt the aggregation process in vitro, including a number of benzothiazoles. To further explore the therapeutic potential of the benzothiazole aggregation inhibitors, we assessed PGL-135 and riluzole in hippocampal slice cultures derived from the R6/2 mouse, confirming their ability to inhibit aggregation with an EC50 of 40 microM in this system. Preliminary pharmacological work showed that PGL-135 was metabolically unstable, and therefore, we conducted a preclinical trial in the R6/2 mouse with riluzole. At the maximum tolerated dose, we achieved steady-state riluzole levels of 100 microM in brain. However, this was insufficient to inhibit aggregation in vivo and we found no improvement in the disease phenotype.",
+ "publisher": "Proceedings of the National Academy of Sciences of the United States of America",
+ "issn": "0027-8424",
+ "date": "1997-04-15",
+ "abstract": "Huntington disease (HD) is associated with abnormal expansions of a CAG repeat close to the 5' end of the IT15 gene. We have assembled a set of 293 HD subjects whose ages of onset were known and sized their HD CAG repeats. These repeats accounted for 69% of the variance of age of onset when we used the most parsimonious model, which relates the logarithm of age of onset to a function of CAG repeat number. Since other familial factors have been proposed to influence the age of onset of HD, we have examined a number of candidate loci. The CAG repeat number on normal chromosomes, the delta2642 polymorphism in the HD gene, and apolipoprotein E genotypes did not affect the age of onset of HD. Although mitochondrial energy production defects in HD have led to suggestions that variants in the mitochondrial genome may be associated with clinical variability in HD, this suggestion was not supported by our preliminary experiments that examined the DdeI mitochondrial restriction fragment length polymorphism at position 10,394. Excitotoxicity has been a favored mechanism to explain the cell death in HD, particularly since intrastriatal injection of excitatory amino acids in animals creates HD-like pathology. Accordingly, we investigated the GluR6 kainate receptor. Of the variance in the age of onset of HD that was not accounted for by the CAG repeats, 13% could be attributed to GluR6 genotype variation. These data implicate GluR6-mediated excitotoxicity in the pathogenesis of HD and highlight the potential importance of this process in other polyglutamine repeat expansion diseases.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16111888"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9108071"
},
{
- "id": "pmid:16096998",
+ "id": "pmid:9106534",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/16096998",
- "title": "Juvenile onset Huntington disease resulting from a very large maternal expansion.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9106534",
+ "title": "Different mechanisms underlie DNA instability in Huntington disease and colorectal cancer.",
"type": "article-journal",
- "doi": "10.1002/ajmg.a.30891",
+ "doi": "",
"authors": [
- ["F A", "Nahhas"],
- ["J", "Garbern"],
- ["K M", "Krajewski"],
- ["B B", "Roa"],
- ["G L", "Feldman"]
+ ["G M", "Goellner"],
+ ["D", "Tester"],
+ ["S", "Thibodeau"],
+ ["E", "Almqvist"],
+ ["Y P", "Goldberg"],
+ ["M R", "Hayden"],
+ ["C T", "McMurray"]
],
- "publisher": "American journal of medical genetics. Part A",
- "issn": "1552-4825",
- "date": "2005-09-01",
- "abstract": "We report a 5(1/2)-year-old girl with a maternal family history of Huntington disease (HD), who presented clinically with unbalanced gait, impaired speech, and increasing difficulty with fine motor control. Onset of symptoms began at the age of 3(1/2) years. The suspected diagnosis of juvenile HD, based upon her family history, was confirmed by DNA analysis. At age 7, the patient died secondary to complications of her underlying disorder. Juvenile-onset Huntington disease is uncommon, predominantly transmitted by fathers and is always associated with very large expansions of the CAG repeat. Interestingly, this patient inherited a large CAG size expansion from her mother, who herself had symptoms of HD at the age of 18. Molecular analysis revealed that the mother had 70 CAG repeats whereas our patient had approximately 130 CAG repeats. This is the largest reported CAG expansion from a maternal transmission that has been confirmed molecularly and it demonstrates that very large expansions can also occur through the maternal lineage.",
+ "publisher": "American journal of human genetics",
+ "issn": "0002-9297",
+ "date": "1997-04-01",
+ "abstract": "Two recent lines of evidence raise the possibility that instability in germ-line or somatic cells arises by a common mechanism that involves defective mismatch repair. Mutations in mismatch-repair proteins are known to cause instability in hereditary nonpolyposis colorectal cancer, instability that is physically similar to germ-line instability observed in Huntington disease (HD). Furthermore, both germ-line and somatic-cell instability are likely to be mitotic defects, the former occurring early in embryogenesis. To test the hypothesis that defective repair is a common prerequisite for instability, we have utilized two disease groups that represent different instability \"conditions.\" Germ-line instability within simple tandem repeats (STR) at 10 loci in 29 HD families were compared with somatic instability at the same loci in 26 colon cancer (CC) patients with identified or suspected defects in mismatch-repair enzymes. HD is known to be caused by expansion within the CAG repeat of the locus, but the extent or pattern of STR instability outside this region has not been examined systematically. We find a distinctly different pattern of STR mutation in the two disease groups, suggesting different mechanisms. Instability in HD is generally confined to a single locus, whereas instability is widespread for the same loci in CC. Our data do not support a causative role for defective mismatch-repair enzymes in instability associated with HD; rather, our data are consistent with a model in which DNA structure may inhibit normal mismatch repair at the expansion site.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16096998"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9106534"
},
{
- "id": "pmid:16082690",
+ "id": "pmid:9002673",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/16082690",
- "title": "Family-based association study of serotonin transporter gene polymorphisms in attention deficit hyperactivity disorder: no evidence for association in UK and Taiwanese samples.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9002673",
+ "title": "Trinucleotide repeats in the human genome: size distributions for all possible triplets and detection of expanded disease alleles in a group of Huntington disease individuals by the repeat expansion detection method.",
"type": "article-journal",
- "doi": "10.1002/ajmg.b.30203",
+ "doi": "10.1093/hmg/6.1.77",
"authors": [
- ["Xiaohui", "Xu"],
- ["Jonathan", "Mill"],
- ["Chi-Ken", "Chen"],
- ["Keeley", "Brookes"],
- ["Eric", "Taylor"],
- ["Philip", "Asherson"]
+ ["S", "Hofferbert"],
+ ["N C", "Schanen"],
+ ["F", "Chehab"],
+ ["U", "Francke"]
],
- "publisher": "American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics",
- "issn": "1552-4841",
- "date": "2005-11-05",
- "abstract": "Five independent studies have reported associations between serotonin transporter gene (5-HTT) polymorphisms and attention deficit hyperactivity disorder (ADHD). Four studies found evidence for association between the long-allele of a 44-base pair insertion/deletion polymorphism (5-HTTLPR), one of the studies found association to a variable number tandem repeat within intron 2, another to the T-allele of a single base pair substitution in the 3'-untranslated regions and another reported preferential transmission of a haplotype of the three markers (long-allele/10-repeat-allele/T-allele). One further study found no evidence for these associations. We investigated the association of these three markers in two samples of ADHD patients from the United Kingdom (n = 197) and Taiwan (n = 212), using within-family tests of association. No association was found between any of the three markers in either of the two populations. Although we found some evidence for the preferential transmission of a rare haplotype (long-allele/9-repeat-allele/T-allele; chi2 = 4.5, P = 0.034), we concluded that this most likely occurred by chance factors alone.",
+ "publisher": "Human molecular genetics",
+ "issn": "0964-6906",
+ "date": "1997-01-01",
+ "abstract": "Using a modified Repeat Expansion Detection (RED) assay, that was optimized for individual oligonucleotides, unrelated individuals were systematically screened for maximal repeat sizes of each of the ten possible trinucleotide repeats. Cloned trinucleotide repeats were generated and used as standards for the detectability of single copy trinucleotide repeat fragments. When the size distributions of trinucleotide repeats were compared to previously reported data, significant differences were found for the CTT repeat, which corresponds to the expanded GAA repeat in Friedreich ataxia, as well as for ATT, CCT and GTT repeats. Since 30-35% of normal individuals have CTG/CAG trinucleotide repeat sizes of 180 bp or more, we investigated the question whether small-scale CTG/CAG repeat expansions are detectable on a population basis by using the RED technique. We blindly screened 20 HD probands with CAG expansions of the HD gene, ranging in size between 120 and 174 bp, and found that a shift to larger CAG size ranges is clearly detectable when comparing the distribution of maximal repeat sizes in the disease group to a control group. Our study, therefore, demonstrates that the application of the RED assay to a population of probands and a population of controls allows the detection of small-scale CTG/CAG repeat expansions in the size range of the expanded HD gene and present in a single allele. We also provide standards and control data for the detection of other trinucleotide repeat expansions.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16082690"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9002673"
},
{
- "id": "pmid:15986189",
+ "id": "pmid:9384710",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/15986189",
- "title": "Association study of a novel functional polymorphism of the serotonin transporter gene in bipolar disorder and suicidal behaviour.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9384710",
+ "title": "Polymorphism within the second intron of the IL-1 receptor antagonist gene in patients with hematopoietic malignancies.",
"type": "article-journal",
- "doi": "10.1007/s00213-005-0046-z",
+ "doi": "",
"authors": [
- ["Vincenzo", "De Luca"],
- ["Subi", "Tharmalingam"],
- ["Nicole", "King"],
- ["John", "Strauss"],
- ["Natalie", "Bulgin"],
- ["James L", "Kennedy"]
+ ["J", "Demeter"],
+ ["G", "Messer"],
+ ["S", "R\u00e4misch"],
+ ["J B", "Mee"],
+ ["F S", "di Giovine"],
+ ["M", "Schmid"],
+ ["F", "Herrmann"],
+ ["F", "Porzsolt"]
],
- "publisher": "Psychopharmacology",
- "issn": "0033-3158",
- "date": "2005-09-29",
- "abstract": "A serotonin transporter gene linked polymorphic region (5-HTTLPR) has been investigated in several genetic association studies, including studies of bipolar disorder (BD) and suicidality. The current study was designed to examine whether the new long (A/G) variant polymorphism of the 5-HTT gene may be associated with the suicide attempts in 305 families with at least one member having BD. No association with history of suicide attempt was found either in the multiallelic HTTLPR (LRS=0.15, df=2, P=0.92), or with the intron 2 variable number tandem repeat (VNTR) polymorphism (LRS=0.87 df=2 P=0.64). When we performed a haplotype analysis, we found no association between suicide attempt and haplotype distribution (LRS=1.84 df=4 P=0.76). These findings suggest that this new polymorphism in the 5-HTT gene may not influence suicidal behaviour in patients with bipolar disorder.",
+ "publisher": "Cytokines and molecular therapy",
+ "issn": "1355-6568",
+ "date": "1996-12-01",
+ "abstract": "Alleles of the IL-1 genes are associated with several autoimmune and inflammatory diseases, where they tend to have a role in the severity of the disease rather than in susceptibility to the disease itself. Allele 2 of the variable number tandem repeat (VNTR) polymorphism in the IL-1 receptor antagonist (IL-1ra) gene was the first marker of the IL-1 cluster to be associated in this way with severity of chronic, systemic and local inflammatory diseases. Because of the role that IL-1 also plays in the pathobiology of certain hematopoietic disorders, we aimed at examining the allelic distribution of the IL-1ra VNTR in leukemias, lymphomas and related malignancies. While in patients with chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL), multiple myeloma (MM) and related disorders, primary acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and Hodgkin's disease (HD), the allelic distribution of IL-1RN was comparable to that seen in healthy control subjects, in a small group of patients with secondary AML the frequency of the IL-1RN*4 allele appeared to be significantly increased.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15986189"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9384710"
},
{
- "id": "pmid:15954918",
+ "id": "pmid:8751857",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/15954918",
- "title": "Interleukin-1 gene cluster polymorphisms predict risk of ESRD.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/8751857",
+ "title": "CAG trinucleotide RNA repeats interact with RNA-binding proteins.",
"type": "article-journal",
- "doi": "10.1111/j.1523-1755.2005.00403.x",
+ "doi": "",
"authors": [
- ["James B", "Wetmore"],
- ["Adriana M", "Hung"],
- ["David H", "Lovett"],
- ["Saunak", "Sen"],
- ["Omer", "Quershy"],
- ["Kirsten L", "Johansen"]
+ ["B A", "McLaughlin"],
+ ["C", "Spencer"],
+ ["J", "Eberwine"]
],
- "publisher": "Kidney international",
- "issn": "0085-2538",
- "date": "2005-07-01",
- "abstract": "Patients with chronic kidney disease manifest an inflammatory state relative to healthy individuals. Inflammation is regulated in part by genes of the interleukin-1 (IL-1) gene cluster. We hypothesized that polymorphisms in this gene cluster may be associated with risk of end-stage renal disease (ESRD).",
+ "publisher": "American journal of human genetics",
+ "issn": "0002-9297",
+ "date": "1996-09-01",
+ "abstract": "Genes associated with several neurological diseases are characterized by the presence of an abnormally long trinucleotide repeat sequence. By way of example, Huntington's disease (HD), is characterized by selective neuronal degeneration associated with the expansion of a polyglutamine-encoding CAG tract. Normally, this CAG tract is comprised of 11-34 repeats, but in HD it is expanded to > 37 repeats in affected individuals. The mechanism by which CAG repeats cause neuronal degeneration is unknown, but it has been speculated that the expansion primarily causes abnormal protein functioning, which in turn causes HD pathology. Other mechanisms, however, have not been ruled out. Interactions between RNA and RNA-binding proteins have previously been shown to play a role in the expression of several eukaryotic genes. Herein, we report the association of cytoplasmic proteins with normal length and extended CAG repeats, using gel shift and UV crosslinking assays. Cytoplasmic protein extracts from several rat brain regions, including the striatum and cortex, sites of neuronal degeneration in HD, contain a 63-kD RNA-binding protein that specifically interacts with these CAG-repeat sequences. These protein-RNA interactions are dependent on the length of the CAG repeat, with longer repeats binding substantially more protein. Two CAG repeat-binding proteins are present in human cortex and striatum; one comigrates with the rat protein at 63 kD, while the other migrates at 49 kD. These data suggest mechanisms by which RNA-binding proteins may be involved in the pathological course of trinucleotide repeat-associated neurological diseases.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15954918"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8751857"
},
{
- "id": "pmid:15906159",
+ "id": "pmid:8659522",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/15906159",
- "title": "Early changes in Huntington's disease patient brains involve alterations in cytoskeletal and synaptic elements.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/8659522",
+ "title": "Phenotypic characterization of individuals with 30-40 CAG repeats in the Huntington disease (HD) gene reveals HD cases with 36 repeats and apparently normal elderly individuals with 36-39 repeats.",
"type": "article-journal",
- "doi": "10.1007/s11068-004-0514-8",
+ "doi": "",
"authors": [
- ["Nicholas A", "DiProspero"],
- ["Er-Yun", "Chen"],
- ["Vinod", "Charles"],
- ["Markus", "Plomann"],
- ["Jeffrey H", "Kordower"],
- ["Danilo A", "Tagle"]
+ ["D C", "Rubinsztein"],
+ ["J", "Leggo"],
+ ["R", "Coles"],
+ ["E", "Almqvist"],
+ ["V", "Biancalana"],
+ ["J J", "Cassiman"],
+ ["K", "Chotai"],
+ ["M", "Connarty"],
+ ["D", "Crauford"],
+ ["A", "Curtis"],
+ ["D", "Curtis"],
+ ["M J", "Davidson"],
+ ["A M", "Differ"],
+ ["C", "Dode"],
+ ["A", "Dodge"],
+ ["M", "Frontali"],
+ ["N G", "Ranen"],
+ ["O C", "Stine"],
+ ["M", "Sherr"],
+ ["M H", "Abbott"],
+ ["M L", "Franz"],
+ ["C A", "Graham"],
+ ["P S", "Harper"],
+ ["J C", "Hedreen"],
+ ["M R", "Hayden"]
],
- "publisher": "Journal of neurocytology",
- "issn": "0300-4864",
- "date": "2004-09-01",
- "abstract": "Huntington's disease (HD) is caused by a polyglutamine repeat expansion in the N-terminus of the huntingtin protein. Huntingtin is normally present in the cytoplasm where it may interact with structural and synaptic elements. The mechanism of HD pathogenesis remains unknown but studies indicate a toxic gain-of-function possibly through aberrant protein interactions. To investigate whether early degenerative changes in HD involve alterations of cytoskeletal and vesicular components, we examined early cellular changes in the frontal cortex of HD presymptomatic (PS), early pathological grade (grade 1) and late-stage (grade 3 and 4) patients as compared to age-matched controls. Morphologic analysis using silver impregnation revealed a progressive decrease in neuronal fiber density and organization in pyramidal cell layers beginning in presymptomatic HD cases. Immunocytochemical analyses for the cytoskeletal markers alpha -tubulin, microtubule-associated protein 2, and phosphorylated neurofilament demonstrated a concomitant loss of staining in early grade cases. Immunoblotting for synaptic proteins revealed a reduction in complexin 2, which was marked in some grade 1 HD cases and significantly reduced in all late stage cases. Interestingly, we demonstrate that two synaptic proteins, dynamin and PACSIN 1, which were unchanged by immunoblotting, showed a striking loss by immunocytochemistry beginning in early stage HD tissue suggesting abnormal distribution of these proteins. We propose that mutant huntingtin affects proteins involved in synaptic function and cytoskeletal integrity before symptoms develop which may influence early disease onset and/or progression.",
+ "publisher": "American journal of human genetics",
+ "issn": "0002-9297",
+ "date": "1996-07-01",
+ "abstract": "Abnormal CAG expansions in the IT-15 gene are associated with Huntington disease (HD). In the diagnostic setting it is necessary to define the limits of the CAG size ranges on normal and HD-associated chromosomes. Most large analyses that defined the limits of the normal and pathological size ranges employed PCR assays, which included the CAG repeats and a CCG repeat tract that was thought to be invariant. Many of these experiments found an overlap between the normal and disease size ranges. Subsequent findings that the CCG repeats vary by 8 trinucleotide lengths suggested that the limits of the normal and disease size ranges should be reevaluated with assays that exclude the CCG polymorphism. Since patients with between 30 and 40 repeats are rare, a consortium was assembled to collect such individuals. All 178 samples were reanalyzed in Cambridge by using assays specific for the CAG repeats. We have optimized methods for reliable sizing of CAG repeats and show cases that demonstrate the dangers of using PCR assays that include both the CAG and CCG polymorphisms. Seven HD patients had 36 repeats, which confirms that this allele is associated with disease. Individuals without apparent symptoms or signs of HD were found at 36 repeats (aged 74, 78, 79, and 87 years), 37 repeats (aged 69 years), 38 repeats (aged 69 and 90 years), and 39 repeats (aged 67, 90, and 95 years). The detailed case histories of an exceptional case from this series will be presented: a 95-year-old man with 39 repeats who did not have classical features of HD. The apparently healthy survival into old age of some individuals with 36-39 repeats suggests that the HD mutation may not always be fully penetrant.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15906159"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8659522"
},
{
- "id": "pmid:15832309",
+ "id": "pmid:8735227",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/15832309",
- "title": "Ancient origin of the CAG expansion causing Huntington disease in a Spanish population.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/8735227",
+ "title": "Reduction in enkephalin and substance P messenger RNA in the striatum of early grade Huntington's disease: a detailed cellular in situ hybridization study.",
"type": "article-journal",
- "doi": "10.1002/humu.20167",
+ "doi": "10.1016/0306-4522(95)00595-1",
"authors": [
- ["Javier", "Garc\u00eda-Planells"],
- ["Juan A", "Burguera"],
- ["Pilar", "Sol\u00eds"],
- ["Jos\u00e9 M", "Mill\u00e1n"],
- ["Dami\u00e1n", "Ginestar"],
- ["Francesc", "Palau"],
- ["Carmen", "Espin\u00f3s"]
+ ["S J", "Augood"],
+ ["R L", "Faull"],
+ ["D R", "Love"],
+ ["P C", "Emson"]
],
- "publisher": "Human mutation",
- "issn": "1098-1004",
- "date": "2005-05-01",
- "abstract": "Huntington disease (HD) is an autosomal dominant neurodegenerative disorder characterized clinically by progressive motor impairment, cognitive decline, and emotional deterioration. The disease is caused by the abnormal expansion of a CAG trinucleotide repeat in the first exon of the huntingtin gene in chromosome 4p16.3. HD is spread worldwide and it is generally accepted that few mutational events account for the origin of the pathogenic CAG expansion in most populations. We have investigated the genetic history of HD mutation in 83 family probands from the Land of Valencia, in Eastern Spain. An analysis of the HD/CCG repeat in informative families suggested that at least two main chromosomes were associated in the Valencian population, one associated with allele 7 (77 mutant chromosomes) and one associated with allele 10 (two mutant chromosomes). Haplotype A-7-A (H1) was observed in 47 out of 48 phase-known mutant chromosomes, obtained by segregation analysis, through the haplotype analysis of rs1313770-HD/CCG-rs82334, as it also was in 120 out of 166 chromosomes constructed by means of the PHASE program. The genetic history and geographical distribution of the main haplotype H1 were both studied by constructing extended haplotypes with flanking short tandem repeats (STRs) D4S106 and D4S3034. We found that we were able to determine the age of the CAG expansion associated with the haplotype H1 as being between 4,700 and 10,000 years ago. Furthermore, we observed a nonhomogenous distribution in the different regions associated with the different extended haplotypes of the ancestral haplotype H1, suggesting that local founder effects have occurred.",
+ "publisher": "Neuroscience",
+ "issn": "0306-4522",
+ "date": "1996-06-01",
+ "abstract": "The expression of enkephalin and substance P messenger RNAs was examined in the caudate-putamen of human post mortem tissue from control and Huntington's disease tissue using in situ hybridization techniques and human specific enkephalin and substance P [35S] oligonucleotides. Macroscopic and microscopic quantification of enkephalin and substance P gene expression was carried out using computer-assisted image analysis. Tissue was collected from six control cases with no sign of neurological disease and six Huntington's disease cases ranging from grades 0 to 3 as determined by neuropathological evaluation. The clinical and pathological diagnosis of Huntington's disease was confirmed unequivocally by genetic analysis of the CAG repeat length in both copies of IT15, the Huntington's disease gene. A marked reduction in both enkephalin and substance P messenger RNAs was detected in all regions of the caudate nucleus and putamen in Huntington's disease grades 2/3 when compared to controls; in the dorsal caudate few enkephalin or substance P messenger RNA-positive cells were detected. For the early grade (0/1) Huntington's disease cases, a heterogeneous reduction in both enkephalin and substance P messenger RNAs were noted; for enkephalin messenger RNA the striatal autoradiograms displayed a conspicuous patchy appearance. Detailed cellular analysis of the dorsal caudate revealed a striking reduction in the number of enkephalin and substance P messenger RNA-positive cells detected and in the intensity of hybridization signal/cell. These data suggest that both the \"indirect\" GABA/enkephalin and \"direct\" GABA/substance P pathways are perturbed very early in the course of the disease and that these early changes in chemical signalling may possibly underlie the onset of clinical symptoms.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15832309"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8735227"
},
{
- "id": "pmid:15811941",
+ "id": "pmid:8714530",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/15811941",
- "title": "RNA interference improves motor and neuropathological abnormalities in a Huntington's disease mouse model.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/8714530",
+ "title": "A reproducible assay of polymerase chain reaction to detect trinucleotide repeat expansion of Huntington's disease and senile chorea.",
"type": "article-journal",
- "doi": "10.1073/pnas.0501507102",
+ "doi": "10.1080/01616412.1996.11740370",
"authors": [
- ["Scott Q", "Harper"],
- ["Patrick D", "Staber"],
- ["Xiaohua", "He"],
- ["Steven L", "Eliason"],
- ["In\u00eas H", "Martins"],
- ["Qinwen", "Mao"],
- ["Linda", "Yang"],
- ["Robert M", "Kotin"],
- ["Henry L", "Paulson"],
- ["Beverly L", "Davidson"]
+ ["M", "Watanabe"],
+ ["K", "Abe"],
+ ["M", "Aoki"],
+ ["T", "Kameya"],
+ ["Y", "Itoyama"],
+ ["M", "Shoji"],
+ ["M", "Ikeda"],
+ ["T", "Iizuka"],
+ ["S", "Hirai"]
],
- "publisher": "Proceedings of the National Academy of Sciences of the United States of America",
- "issn": "0027-8424",
- "date": "2005-04-05",
- "abstract": "Huntington's disease (HD) is a fatal, dominant neurogenetic disorder. HD results from polyglutamine repeat expansion (CAG codon, Q) in exon 1 of HD, conferring a toxic gain of function on the protein huntingtin (htt). Currently, no preventative treatment exists for HD. RNA interference (RNAi) has emerged as a potential therapeutic tool for treating dominant diseases by directly reducing disease gene expression. Here, we show that RNAi directed against mutant human htt reduced htt mRNA and protein expression in cell culture and in HD mouse brain. Importantly, htt gene silencing improved behavioral and neuropathological abnormalities associated with HD. Our data provide support for the further development of RNAi for HD therapy.",
+ "publisher": "Neurological research",
+ "issn": "0161-6412",
+ "date": "1996-02-01",
+ "abstract": "A simple and reproducible method of polymerase chain reaction (PCR) assay was established to detect trinucleotide repeat expansion for Huntington's disease (HD) using a new DNA polymerase and buffer system. The system consists of an extremely heat stable DNA polymerase (Pfu), and a buffer supplemented with ammonium sulfate and dimethyl sulfoxide. Previous methods to amplify expanded alleles for HD have been very complex in PCR conditions, but the reproducibility was sometimes very low because of repetitive sequences around the primer sequences. With the present method, strong bands for the disease alleles were reproducibly visible in a conventional agarose gel stained with ethidium bromide without using isotopes. Three cases with sporadic HD and a case with senile chorea showed expanded alleles for HD with smaller sizes of the expansion than cases with typical HD. These results showed that the present method provides a simple and reproducible way to detect HD allele, and some cases with sporadic HD and senile chorea had expanded HD alleles.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15811941"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8714530"
},
{
- "id": "pmid:15764008",
+ "id": "pmid:8614526",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/15764008",
- "title": "Yugoslav HD phenocopies analyzed on the presence of mutations in PrP, ferritin, and Jp-3 genes.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/8614526",
+ "title": "Trinucleotide repeat length and clinical progression in Huntington's disease.",
"type": "article-journal",
- "doi": "10.1080/00207450590519571",
+ "doi": "10.1212/wnl.46.2.527",
"authors": [
- ["Milica", "Keckarevi\u0107"],
- ["Dusanka", "Savi\u0107"],
- ["Marina", "Svetel"],
- ["Vladimir", "Kosti\u0107"],
- ["Slobodanka", "Vukosavi\u0107"],
- ["Stanka", "Romac"]
+ ["J", "Brandt"],
+ ["F W", "Bylsma"],
+ ["R", "Gross"],
+ ["O C", "Stine"],
+ ["N", "Ranen"],
+ ["C A", "Ross"]
],
- "publisher": "The International journal of neuroscience",
- "issn": "0020-7454",
- "date": "2005-02-01",
- "abstract": "Huntington disease (HD) is a well-defined autosomal dominant neurodegenerative disease caused by CAG repeat expansions in HD gene. There are a significant number of HD cases where this mutation was not found and such cases are named HD-like phenotype (HDL). This article reports 48 patients with HDL phenotype. Patients were analyzed on the presence of mutations in prion (PrP), ferritin and junctophilin-3 (JP-3) genes. None of the patients showed the presence of the mutation in analyzed genes. This could suggest that there is some other gene/genes where the mutation can cause the disease with clinical features of HD.",
+ "publisher": "Neurology",
+ "issn": "0028-3878",
+ "date": "1996-02-01",
+ "abstract": "We examined the relationship between length of the trinucleotide (CAG) repeat at IT-15 and clinical progression of Huntington's disease in 46 mildly to moderately affected patients over a 2-year interval. Patients were divided into those with short mutations (37 to 46 repeats; n = 25) and those with long mutations (> or = 47 repeats; n = 21). Patients with long repeat lengths had earlier age at onset and were younger and less functionally impaired than those with short repeats at the initial visit, but the groups did not differ in severity of neurologic or cognitive impairment. However, the long-repeat group displayed significantly greater decline in both neurologic and cognitive functioning over the 2-year follow-up period. The length of the CAG repeat correlated highly with age at onset (r = -0.72, p < 0.001) and was a strong predictor of decline in both neurologic and cognitive function. The mechanism of gene action, and the means by which longer expansions result in a more malignant disease process, remain to be elucidated.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15764008"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8614526"
},
{
- "id": "pmid:15716522",
+ "id": "pmid:8985734",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/15716522",
- "title": "Incidence and mutation rates of Huntington's disease in Spain: experience of 9 years of direct genetic testing.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/8985734",
+ "title": "Relationships of the 2642 deletion polymorphism (delta 2642) in the huntingtin gene with the CAG repeat expansion length and age at onset of the disease.",
"type": "article-journal",
- "doi": "10.1136/jnnp.2004.036806",
+ "doi": "",
"authors": [
- ["M A", "Ramos-Arroyo"],
- ["S", "Moreno"],
- ["A", "Valiente"]
+ ["G", "Lucotte"],
+ ["N", "G\u00e9rard"],
+ ["P", "Roubertoux"],
+ ["I", "Schmitt"],
+ ["O", "Riess"]
],
- "publisher": "Journal of neurology, neurosurgery, and psychiatry",
- "issn": "0022-3050",
- "date": "2005-03-01",
- "abstract": "Prior to the discovery of the Huntington's disease (HD) mutation, the prevalence, incidence, and new mutation rates for this disease were based on the presence of progressive choreic movements and a positive family history.",
+ "publisher": "Genetic counseling (Geneva, Switzerland)",
+ "issn": "1015-8146",
+ "date": "1996-01-01",
+ "abstract": "The deletion of 3bp at codon positions 2642-2645 (delta 2642) of the gene mutated in Huntington's disease (HD) was analysed on the normal (N) and HD chromosomes of 79 French families affected with HD, and previously typed for the (CAG)n repeats. delta 2642 Polymorphism has been found over-represented on HD chromosomes, the relative risk of HD with the deletion being at a value of 8.26. In this study, the presence of the deleted allele on HD chromosomes increases the (CAG)n number (47.93 +/- 1.80 versus 43.50 +/- 2.78) and decreases the age of onset (41.34 +/- 2.09 versus 36.90 +/- 2.41) in the patients with versus without delta 2642; so the deletion may add to the severity of the disease. Our studies of delta 2642 on N chromosomes confirm that the deletion event occurs on N chromosomes with a (CAG)n allele length at the upper end of the normal size range.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15716522"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8985734"
},
{
- "id": "pmid:15704211",
+ "id": "pmid:8804464",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/15704211",
- "title": "Mitochondrial impairment in patients and asymptomatic mutation carriers of Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/8804464",
+ "title": "The relevance of VDJ PCR protocols in detecting B-cell clonal expansion in lymphomas and other lymphoproliferative disorders.",
"type": "article-journal",
- "doi": "10.1002/mds.20373",
+ "doi": "10.1177/030089169508100603",
"authors": [
- ["Carsten", "Saft"],
- ["Jochen", "Zange"],
- ["J\u00fcrgen", "Andrich"],
- ["Klaus", "M\u00fcller"],
- ["Katrin", "Lindenberg"],
- ["Bernhard", "Landwehrmeyer"],
- ["Matthias", "Vorgerd"],
- ["Peter H", "Kraus"],
- ["Horst", "Przuntek"],
- ["Ludger", "Sch\u00f6ls"]
- ],
- "publisher": "Movement disorders : official journal of the Movement Disorder Society",
- "issn": "0885-3185",
- "date": "2005-06-01",
- "abstract": "Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the IT-15 gene; however, it remains unknown how the mutation leads to selective neurodegeneration. Several lines of evidence suggest impaired mitochondrial function as a component of the neurodegenerative process in HD. We assessed energy metabolism in the skeletal muscle of 15 HD patients and 12 asymptomatic mutation carriers in vivo using 31P magnetic resonance spectroscopy. Phosphocreatine recovery after exercise is a direct measure of ATP synthesis and was slowed significantly in HD patients and mutation carriers in comparison to age- and gender-matched healthy controls. We found that oxidative function is impaired to a similar extent in manifest HD patients and asymptomatic mutation carriers. Our findings suggest that mitochondrial dysfunction is an early and persistent component of the pathophysiology of HD.",
+ ["V", "De Re"],
+ ["S", "De Vita"],
+ ["A", "Carbone"],
+ ["G", "Ferraccioli"],
+ ["A", "Gloghini"],
+ ["A", "Marzotto"],
+ ["B", "Pivetta"],
+ ["R", "Dolcetti"],
+ ["M", "Boiocchi"]
+ ],
+ "publisher": "Tumori",
+ "issn": "0300-8916",
+ "date": "1995-01-01",
+ "abstract": "The detection of immunoglobulin heavy chain variable (VH)-diversity (DH)-joining (JH) region gene rearrangement by polymerase chain reaction (VDJ PCR) has been recently proposed as a rapid approach to assess B-cell clonality in lymphoproliferative disorders. The aim of the present study was to determine the efficacy of VDJ PCR in a wide spectrum of lymphoproliferative disorders previously characterized by immunohistochemistry and Southern blot (SB).",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15704211"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8804464"
},
{
- "id": "pmid:15635668",
+ "id": "pmid:7576661",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/15635668",
- "title": "Serotonin transporter intron 2 polymorphism associated with rigid-compulsive behaviors in Dutch individuals with pervasive developmental disorder.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/7576661",
+ "title": "CAG expansion affects the expression of mutant Huntingtin in the Huntington's disease brain.",
"type": "article-journal",
- "doi": "10.1002/ajmg.b.30122",
+ "doi": "10.1016/0896-6273(95)90106-x",
"authors": [
- ["Erik J", "Mulder"],
- ["George M", "Anderson"],
- ["Ido P", "Kema"],
- ["Astrid M", "Brugman"],
- ["Cees E J", "Ketelaars"],
- ["Annelies", "de Bildt"],
- ["Natasja D J", "van Lang"],
- ["Johan A", "den Boer"],
- ["Ruud B", "Minderaa"]
+ ["N", "Aronin"],
+ ["K", "Chase"],
+ ["C", "Young"],
+ ["E", "Sapp"],
+ ["C", "Schwarz"],
+ ["N", "Matta"],
+ ["R", "Kornreich"],
+ ["B", "Landwehrmeyer"],
+ ["E", "Bird"],
+ ["M F", "Beal"]
],
- "publisher": "American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics",
- "issn": "1552-4841",
- "date": "2005-02-05",
- "abstract": "Two putatively functional polymorphisms of the serotonin transporter gene (HTT, SLC6A4) were examined for associations with risk for pervasive developmental disorders (PDDs) and specific autism phenotypes. Dutch patients diagnosed with PDD (N = 125, age range 5-20 years, DSM-IV-TR based criteria, ADI-R and ADOS behavioral assessments) and their parents (N = 230) were genotyped for promoter ins/del (5-HTTLPR) and intron 2 variable number of tandem repeats (VNTR) alleles. Using the transmission disequilibrium test (TDT), no disorder-specific preferential transmission of promoter (long and short) or intron 2 (10- and 12-repeat) alleles was observed. However, multivariate analysis of continuous autism-related behavioral measures revealed that subjects with intron 2 12/12 genotype were significantly more impaired in the rigid-compulsive domain (P = 0.008). Quantitative TDT (QTDT) analysis also showed significant association of the intron 2 VNTR 12-repeat allele with rigid-compulsive behavior (P = 0.015). These results suggest that intron 2 VNTR alleles or nearby polymorphisms in linkage disequilibrium may play a role in specific aspects of the behavioral phenotype of autism.",
+ "publisher": "Neuron",
+ "issn": "0896-6273",
+ "date": "1995-11-01",
+ "abstract": "A trinucleotide repeat (CAG) expansion in the huntingtin gene causes Huntington's disease (HD). In brain tissue from HD heterozygotes with adult onset and more clinically severe juvenile onset, where the largest expansions occur, a mutant protein of equivalent intensity to wild-type huntingtin was detected in cortical synaptosomes, indicating that a mutant species is synthesized and transported with the normal protein to nerve endings. The increased size of mutant huntingtin relative to the wild type was highly correlated with CAG repeat expansion, thereby linking an altered electrophoretic mobility of the mutant protein to its abnormal function. Mutant huntingtin appeared in gray and white matter with no difference in expression in affected regions. The mutant protein was broader than the wild type and in 6 of 11 juvenile cases resolved as a complex of bands, consistent with evidence at the DNA level for somatic mosaicism. Thus, HD pathogenesis results from a gain of function by an aberrant protein that is widely expressed in brain and is harmful only to some neurons.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15635668"
-},
-{
- "id": "pmid:15496421",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/15496421",
- "note": "WARNING: Couldn't parse Manubot response: list index out of range"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7576661"
},
{
- "id": "pmid:15468075",
+ "id": "pmid:7668287",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/15468075",
- "title": "Huntington's Disease-like 2 (HDL2) in North America and Japan.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/7668287",
+ "title": "Anticipation and instability of IT-15 (CAG)n repeats in parent-offspring pairs with Huntington disease.",
"type": "article-journal",
- "doi": "10.1002/ana.20248",
+ "doi": "",
"authors": [
- ["Russell L", "Margolis"],
- ["Susan E", "Holmes"],
- ["Adam", "Rosenblatt"],
- ["Lisa", "Gourley"],
- ["Elizabeth", "O'Hearn"],
- ["Christopher A", "Ross"],
- ["William K", "Seltzer"],
- ["Ruth H", "Walker"],
- ["Tetsuo", "Ashizawa"],
- ["Astrid", "Rasmussen"],
- ["Michael", "Hayden"],
- ["Elisabeth W", "Almqvist"],
- ["Juliette", "Harris"],
- ["Stanley", "Fahn"],
- ["Marcy E", "MacDonald"],
- ["Jayalakshmi", "Mysore"],
- ["Takayoshi", "Shimohata"],
- ["Shoji", "Tsuji"],
- ["Nicholas", "Potter"],
- ["Kazuhiro", "Nakaso"],
- ["Yoshiki", "Adachi"],
- ["Kenji", "Nakashima"],
- ["Thomas", "Bird"],
- ["Amanda", "Krause"],
- ["Penny", "Greenstein"]
+ ["N G", "Ranen"],
+ ["O C", "Stine"],
+ ["M H", "Abbott"],
+ ["M", "Sherr"],
+ ["A M", "Codori"],
+ ["M L", "Franz"],
+ ["N I", "Chao"],
+ ["A S", "Chung"],
+ ["N", "Pleasant"],
+ ["C", "Callahan"]
],
- "publisher": "Annals of neurology",
- "issn": "0364-5134",
- "date": "2004-11-01",
- "abstract": "Huntington's Disease-like 2 (HDL2) is a progressive, autosomal dominant, neurodegenerative disorder with marked clinical and pathological similarities to Huntington's disease (HD). The causal mutation is a CTG/CAG expansion mutation on chromosome 16q24.3, in a variably spliced exon of junctophilin-3. The frequency of HDL2 was determined in nine independent series of patients referred for HD testing or selected for the presence of an HD-like phenotype in North America or Japan. The repeat length, ancestry, and age of onset of all North American HDL2 cases were determined. The results show that HDL2 is very rare, with a frequency of 0 to 15% among patients in the nine case series with an HD-like presentation who do not have the HD mutation. HDL2 is predominantly, and perhaps exclusively, found in individuals of African ancestry. Repeat expansions ranged from 44 to 57 triplets, with length instability in maternal transmission detected in a repeat of r2=0.29, p=0.0098). The results further support the evidence that the repeat expansion at the chromosome 16q24.3 locus is the direct cause of HDL2 and provide preliminary guidelines for the genetic testing of patients with an HD-like phenotype.",
+ "publisher": "American journal of human genetics",
+ "issn": "0002-9297",
+ "date": "1995-09-01",
+ "abstract": "Huntington disease (HD) is an autosomal dominant degenerative disorder caused by an expanded and unstable trinucleotide repeat (CAG)n in a gene (IT-15) on chromosome 4. HD exhibits genetic anticipation--earlier onset in successive generations within a pedigree. From a population-based clinical sample, we ascertained parent-offspring pairs with expanded alleles, to examine the intergenerational behavior of the trinucleotide repeat and its relationship to anticipation. We find that the change in repeat length with paternal transmission is significantly correlated with the change in age at onset between the father and offspring. When expanded triplet repeats of affected parents are separated by median repeat length, we find that the longer paternal and maternal repeats are both more unstable on transmission. However, unlike in paternal transmission, in which longer expanded repeats display greater net expansion than do shorter expanded repeats, in maternal transmission there is no mean change in repeat length for either longer or shorter expanded repeats. We also confirmed the inverse relationship between repeat length and age at onset, the higher frequency of juvenile-onset cases arising from paternal transmission, anticipation as a phenomenon of paternal transmission, and greater expansion of the trinucleotide repeat with paternal transmission. Stepwise multiple regression indicates that, in addition to repeat length of offspring, age at onset of affected parent and sex of affected parent contribute significantly to the variance in age at onset of the offspring. Thus, in addition to triplet repeat length, other factors, which could act as environmental factors, genetic factors, or both, contribute to age at onset. Our data establish that further expansion of paternal repeats within the affected range provides a biological basis of anticipation in HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15468075"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7668287"
},
{
- "id": "pmid:15372528",
+ "id": "pmid:7668260",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/15372528",
- "title": "Mosaicism of the CAG repeat sequence in the Huntington disease gene in a pair of monozygotic twins.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/7668260",
+ "title": "Sex-dependent mechanisms for expansions and contractions of the CAG repeat on affected Huntington disease chromosomes.",
"type": "article-journal",
- "doi": "10.1002/ajmg.a.30128",
+ "doi": "",
"authors": [
- ["Anne", "N\u00f8rrem\u00f8lle"],
- ["Lis", "Hasholt"],
- ["Cathrine Bie", "Petersen"],
- ["Hans", "Eiberg"],
- ["Steen G", "Hasselbalch"],
- ["Peter", "Gideon"],
- ["J\u00f8rgen E", "Nielsen"],
- ["Sven Asger", "S\u00f8rensen"]
+ ["B", "Kremer"],
+ ["E", "Almqvist"],
+ ["J", "Theilmann"],
+ ["N", "Spence"],
+ ["H", "Telenius"],
+ ["Y P", "Goldberg"],
+ ["M R", "Hayden"]
],
- "publisher": "American journal of medical genetics. Part A",
- "issn": "1552-4825",
- "date": "2004-10-01",
- "abstract": "We report on a pair of monozygotic twins belonging to a family segregating Huntington disease (HD). In routine DNA analysis of blood cells, they displayed three alleles of the CAG repeat sequence in the HD gene. Two different cell lines, carrying the normal allele together with either an expanded allele with 47 CAGs or an intermediate allele with 37 CAGs, were detected in blood and buccal epithelium from both twins. To our knowledge, this is the first case described of HD gene CAG repeat length mosaicism in blood cells. Haplotype analysis established that the 37 CAG allele most likely arose by contraction of the maternal 47 CAG allele. The contraction must have taken place postzygotically, possibly at a very early stage of development, and probably before separation of the twins. One of the twins has presented symptoms of HD for 4 years; his skin fibroblasts and hair roots carried only the cell line with the 47 CAG repeat allele. The other twin, who is without symptoms at present, displayed mosaicism in skin fibroblasts and hair roots. If the proportion of the two cell lines in the brain of each twin resembles that of their hair roots (another tissue originating from the ectoderm), the mosaicism in the unaffected twin would mean that only a part of his brain cells carried the expanded allele, which could explain why he, in contrast to his brother, has no symptoms at this time.",
+ "publisher": "American journal of human genetics",
+ "issn": "0002-9297",
+ "date": "1995-08-01",
+ "abstract": "A total of 254 affected parent-child pairs with Huntington disease (HD) and 440 parent-child pairs with CAG size in the normal range were assessed to determine the nature and frequency of intergenerational CAG changes in the HD gene. Intergenerational CAG changes are extremely rare (3/440 [0.68%]) on normal chromosomes. In contrast, on HD chromosomes, changes in CAG size occur in approximately 70% of meioses on HD chromosomes, with expansions accounting for 73% of these changes. These intergenerational CAG changes make a significant but minor contribution to changes in age at onset (r2 = .19). The size of the CAG repeat influenced larger intergenerational expansions (> 7 CAG repeats), but the likelihood of smaller expansions or contractions was not influenced by CAG size. Large expansions (> 7 CAG repeats) occur almost exclusively through paternal transmission (0.96%; P < 10(-7)), while offspring of affected mothers are more likely to show no change (P = .01) or contractions in CAG size (P = .002). This study demonstrates that sex of the transmitting parent is the major determinant for CAG intergenerational changes in the HD gene. Similar paternal sex effects are seen in the evolution of new mutations for HD from intermediate alleles and for large expansions on affected chromosomes. Affected mothers almost never transmit a significantly expanded CAG repeat, despite the fact that many have similar large-sized alleles, compared with affected fathers. The sex-dependent effects of major expansion and contractions of the CAG repeat in the HD gene implicate different effects of gametogenesis, in males versus females, on intergenerational CAG repeat stability.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15372528"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7668260"
},
{
- "id": "pmid:15345132",
+ "id": "pmid:7639626",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/15345132",
- "title": "In vitro proliferation and expansion of hematopoietic progenitors present in mobilized peripheral blood from normal subjects and cancer patients.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/7639626",
+ "title": "Correlations between triplet repeat expansion and clinical features in Huntington's disease.",
"type": "article-journal",
- "doi": "10.1089/scd.2004.13.382",
+ "doi": "10.1001/archneur.1995.00540320021009",
"authors": [
- ["Guadalupe", "Mart\u00ednez-Jaramillo"],
- ["Patricia", "Flores-Guzm\u00e1n"],
- ["Juan Jos\u00e9", "Montesinos"],
- ["Sandra", "Quintana"],
- ["Javier", "Bautista"],
- ["Elizabeth", "S\u00e1nchez-Valle"],
- ["Mar\u00eda", "de Jes\u00fas Nambo"],
- ["Hector", "Mayani"]
+ ["S", "Claes"],
+ ["K", "Van Zand"],
+ ["E", "Legius"],
+ ["R", "Dom"],
+ ["M", "Malfroid"],
+ ["F", "Baro"],
+ ["J", "Godderis"],
+ ["J J", "Cassiman"]
],
- "publisher": "Stem cells and development",
- "issn": "1547-3287",
- "date": "2004-08-01",
- "abstract": "In the present study, we have assessed, in a comparative manner, the in vitro proliferation and expansion potentials of hematopoietic progenitor cells (HPC) present in mobilized peripheral blood from normal subjects (MPB-n; n = 18) and cancer patients (MPB-c; n = 18). The latter included patients with breast cancer (BrCa; n = 8), Hodgkin disease (HD; n = 4), non-Hodgkin lymphoma (NHL; n = 3), and acute myeloid leukemia (AML; n = 3). Progenitor cells from normal bone marrow (BM) and umbilical cord blood (UCB) were included as controls. HPC, enriched by a negative selection procedure, were cultured for 25 days, in serum-free liquid media in the presence of a cytokine combination including early- and late-acting cytokines. Our results demonstrate that the in vitro biological properties of progenitor cells present in MPB differ, depending on whether they are derived from healthy individuals, from patients with solid tumors, or from patients with hematological neoplasias. Among all cell sources analyzed, UCB-derived progenitors showed the greatest proliferation and expansion potentials (1000-fold increase in total cell numbers on day 15, and a 22-fold increase in myeloid progenitor cell numbers, at day 10). Progenitor cells present in MPB from hematologically normal individuals showed proliferation and expansion potentials comparable to those of HPC from normal BM (500-fold increase in total cell numbers on day 15, and a 14-fold increase in myeloid progenitor cell numbers, at day 10). The proliferation/expansion potentials of MPB progenitors from BrCa patients were also within the normal range, although in the lower levels (327-fold increase in total cell numbers, on day 15, and 11.8-fold increase in myeloid progenitors, at day 10). In contrast, progenitors present in MPB from patients with HD, NHL, and especially AML, showed reduced in vitro capacities (119-, 102-, and 51-fold increase in total cell numbers, respectively; and 8-, 4-, and 2.6-fold increase in myeloid progenitor cells, respectively). To our knowledge, this is the first report in which the in vitro proliferation and expansion potentials of HPC from MPB from normal subjects and cancer patients are assessed simultaneously in a comparative manner.",
+ "publisher": "Archives of neurology",
+ "issn": "0003-9942",
+ "date": "1995-08-01",
+ "abstract": "To investigate possible correlations between the length of the (CAG)n trinucleotide repeat in Hungtington's disease gene IT15 and clinical features (age at onset, symptoms at onset, and mode of progression) in Huntington's disease.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15345132"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7639626"
},
{
- "id": "pmid:15254954",
+ "id": "pmid:7675777",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/15254954",
- "title": "Markedly asymmetrical parkinsonism as a leading feature of adult-onset Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/7675777",
+ "title": "Epstein-Bar virus and progression of non-Hodgkin's lymphoma to Ki-1-positive, anaplastic large cell phenotype.",
"type": "article-journal",
- "doi": "10.1002/mds.20093",
+ "doi": "",
"authors": [
- ["Shih-Ching", "Wang"],
- ["Guey-Jen", "Lee-Chen"],
- ["Cheng-Kung", "Wang"],
- ["Chiung-Mei", "Chen"],
- ["Lok-Ming", "Tang"],
- ["Yih-Ru", "Wu"]
+ ["J A", "DiGiuseppe"],
+ ["T C", "Wu"],
+ ["B A", "Zehnbauer"],
+ ["P R", "McDowell"],
+ ["J M", "Barletta"],
+ ["R F", "Ambinder"],
+ ["R B", "Mann"]
],
- "publisher": "Movement disorders : official journal of the Movement Disorder Society",
- "issn": "0885-3185",
- "date": "2004-07-01",
- "abstract": "We report on a 28-year-old man who presented with right hand tremor, bradykinesia, and rigidity of his right side extremities. Our case report emphasizes that markedly asymmetrical parkinsonism can be an initial presentation of adult-onset Huntington's disease (HD), and different clinical presentations can be observed in members of an individual HD family with the same CAG repeat length.",
+ "publisher": "Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc",
+ "issn": "0893-3952",
+ "date": "1995-06-01",
+ "abstract": "Epstein-Barr virus (EBV) has been implicated in the pathogenesis of a variety of lymphoproliferative disorders (LPDs) including endemic Burkitt's lymphoma, Hodgkin's disease (HD), HIV-associated non-Hodgkin's lymphomas (NHLs), and LPDs arising in immunosuppressed transplant patients. More recently, EBV has been associated with Ki-1-positive anaplastic large cell lymphoma (ALCL), a recently described NHL that shares with HD expression of the CD30 antigen Ki-1. Because EBV has been shown to induce Ki-1 expression in vitro, and ALCL has been diagnosed in patients with prior or concurrent HD or NHL, it has been proposed that EBV may mediate progression of a \"primary\" lymphoma to a \"secondary\" ALCL. We report a case in which an AIDS-associated, Ki-1-negative, large-cell immunoblastic lymphoma progressed to a Ki-1 positive ALCL. Analysis of the immunoglobulin heavy chain locus revealed a clonal relationship between these morphologically and immunophenotypically distinct tumors. Although EBV was absent from the original large-cell immunoblastic lymphoma as assessed by in situ hybridization for EBV-encoded small RNA1 (EBER1), polymerase chain reaction for EBNA-1, immunocytochemistry for latent membrane protein 1, and Southern blot hybridization for EBV terminal repeat sequences, all for techniques confirmed the presence of EBV in the secondary ALCL. Moreover, analysis of EBV terminal repeat sequences indicated that the ALCL resulted from expansion of a single EBV-infected clone. These data suggest that EBV may mediate progression of NHL to Ki-1-positive ALCL, and that in some instances, EBV may be involved in the later stages of clonal progression of NHL.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15254954"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7675777"
},
{
- "id": "pmid:15229244",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/15229244",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:15229244']' timed out after 3 seconds"
+ "id": "pmid:7898693",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/7898693",
+ "title": "Hereditary late-onset chorea without significant dementia: genetic evidence for substantial phenotypic variation in Huntington's disease.",
+ "type": "article-journal",
+ "doi": "10.1212/wnl.45.3.443",
+ "authors": [
+ ["J W", "Britton"],
+ ["R J", "Uitti"],
+ ["J E", "Ahlskog"],
+ ["R G", "Robinson"],
+ ["B", "Kremer"],
+ ["M R", "Hayden"]
+ ],
+ "publisher": "Neurology",
+ "issn": "0028-3878",
+ "date": "1995-03-01",
+ "abstract": "We examined five individuals and obtained information concerning six other members from two unrelated families, nearly all of whom developed chorea after age 50 (one patient developed chorea at age 40). The severity of chorea progressed in all patients and became disabling in some individuals approximately 15 years after onset. Cognitive impairment was absent or minimal. All five examined patients were cognitively normal, even 10 to 30 years following the onset of chorea. Formal neuropsychometric testing demonstrated mild cognitive impairment in two individuals. Nevertheless, all patients were able to maintain employment or carry on with their usual household tasks until chorea was severe. One individual first became demented 30 years after the onset of chorea. Neuroimaging (with CT or MRI) in four patients failed to demonstrate significant caudate or putaminal atrophy 8 to 15 years following the onset of chorea. Three other family members (who were not available for examination) were said to have suffered chorea (without any mental decline) beginning after age 50, with subsequent survival of 20 years (in one) and 30 years (in two). Given this constellation of history and findings, three experienced neurologists and two medical geneticists concluded that these patients had a familial chorea syndrome distinct from Huntington's disease (HD). However, genetic analysis of the trinucleotide (CAG) repeat length associated with HD (in 4p16.3) determined repeat lengths of 44 and 46 in four patients tested (within the HD range). We conclude that these patients have HD and that such families represent further convincing examples of significant phenotypic variation for HD.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7898693"
},
{
- "id": "pmid:15147313",
+ "id": "pmid:7881406",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/15147313",
- "title": "Dendritic spine pathology and deficits in experience-dependent dendritic plasticity in R6/1 Huntington's disease transgenic mice.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/7881406",
+ "title": "DNA haplotype analysis of Huntington disease reveals clues to the origins and mechanisms of CAG expansion and reasons for geographic variations of prevalence.",
"type": "article-journal",
- "doi": "10.1111/j.0953-816x.2004.03374.x",
+ "doi": "10.1093/hmg/3.12.2103",
"authors": [
- ["Tara L", "Spires"],
- ["Helen E", "Grote"],
- ["Sylvia", "Garry"],
- ["Patricia M", "Cordery"],
- ["Anton", "Van Dellen"],
- ["Colin", "Blakemore"],
- ["Anthony J", "Hannan"]
+ ["F", "Squitieri"],
+ ["S E", "Andrew"],
+ ["Y P", "Goldberg"],
+ ["B", "Kremer"],
+ ["N", "Spence"],
+ ["J", "Zeisler"],
+ ["K", "Nichol"],
+ ["J", "Theilmann"],
+ ["J", "Greenberg"],
+ ["J", "Goto"]
],
- "publisher": "The European journal of neuroscience",
- "issn": "0953-816X",
- "date": "2004-05-01",
- "abstract": "Huntington's disease (HD) is a fatal neurodegenerative disease caused by a CAG repeat expansion coding for an expanded polyglutamine tract in the huntingtin protein. Dendritic abnormalities occur in human HD patients and in several transgenic mouse models of the disease. In this study, we examine, for the first time, dendrite and spine pathology in the R6/1 mouse model of HD, which mimics neurodegeneration seen in human HD. Enriching the environment of HD transgenic mice delays the onset of symptoms, so we also examine the effects of enrichment on dendrite pathology. Golgi-impregnated tissue from symptomatic R6/1 HD mice reveals a decrease in dendritic spine density and dendritic spine length in striatal medium spiny neurons and cortical pyramidal neurons. HD also causes a specific reduction in the proportion of bifurcated dendritic spines on basal dendrites of cortical pyramidal neurons. No differences in soma size, recurving distal dendrites, or dendritic branching were observed. Although home-cage environmental enrichment from 1 to 8 months of age increases spine density in wild-type mice, it has no effect on the spine pathology in HD mice. These results show that dendritic spine pathology in R6/1 HD mice resembles degenerative changes seen in human HD and in other transgenic mouse models of the disease. We thus provide further evidence that the HD mutation disrupts the connectivity in both neostriatum and cerebral cortex, which will contribute to motor and cognitive disease symptoms. Furthermore, we demonstrate that Huntington's disease pathology interferes with the normal plastic response of dendritic spines to environmental enrichment.",
+ "publisher": "Human molecular genetics",
+ "issn": "0964-6906",
+ "date": "1994-12-01",
+ "abstract": "This study of allelic association using three intra- and two extragenic markers within 150 kb of the Huntington disease (HD) mutation has provided evidence for linkage disequilibrium for four of five markers. Haplotype analysis of 67 HD families using markers in strong linkage disequilibrium with HD identified two haplotypes underlying 77.6% of HD chromosomes. Normal chromosomes with these two haplotypes had a mean number of CAG repeats significantly larger than and an altered distribution of CAG repeats compared with other normal chromosomes. Furthermore, haplotype analysis of five new mutation families reveals that HD has arisen on these same two chromosomal haplotypes. These findings suggest that HD arises more frequently on chromosomes with specific DNA haplotypes and higher CAG repeat lengths. We then studied CAG and CCG repeat lengths in the HD gene on 896 control chromosomes from different ancestries to determine whether the markedly reduced frequency of HD in Finland, Japan, China and African Blacks is associated with an altered frequency of DNA haplotypes and subsequently lower CAG lengths on control chromosomes compared to populations of Western European descent. The results show a highly significant inverse relationship between CAG and CCG repeat lengths. In populations with lowered prevalence rates of HD, CAG repeat lengths are smaller and the distribution of CCG alleles is markedly different from Western European populations. These findings suggest that, in addition to European emigration, new mutations make a contribution to geographical variation of prevalence rates and is consistent with a multistep model of HD developing from normal chromosomes with higher CAG repeat lengths.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15147313"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7881406"
},
{
- "id": "pmid:15094787",
+ "id": "pmid:7969980",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/15094787",
- "title": "Variants of the serotonin transporter gene (SLC6A4) significantly contribute to hyperserotonemia in autism.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/7969980",
+ "title": "Normal CAG repeat length in the Huntington's disease gene in senile chorea.",
"type": "article-journal",
- "doi": "10.1038/sj.mp.4001409",
+ "doi": "10.1212/wnl.44.11.2183",
"authors": [
- ["A M", "Coutinho"],
- ["G", "Oliveira"],
- ["T", "Morgadinho"],
- ["C", "Fesel"],
- ["T R", "Macedo"],
- ["C", "Bento"],
- ["C", "Marques"],
- ["A", "Ata\u00edde"],
- ["T", "Miguel"],
- ["L", "Borges"],
- ["A M", "Vicente"]
+ ["H", "Shinotoh"],
+ ["D B", "Calne"],
+ ["B", "Snow"],
+ ["M", "Hayward"],
+ ["B", "Kremer"],
+ ["J", "Theilmann"],
+ ["M R", "Hayden"]
],
- "publisher": "Molecular psychiatry",
- "issn": "1359-4184",
- "date": "2004-03-01",
- "abstract": "The role of the serotonin system in the etiology and pathogenesis of autism spectrum disorders (ASD) is not clearly defined. High levels of platelet serotonin (5-HT) have been consistently found in a proportion of patients, and it is known that specific 5-HT transporter gene (SLC6A4) variants modulate transporter reuptake function, therefore possibly influencing the occurrence of hyperserotonemia in a subset of autistic patients. We have examined the association of platelet serotonin levels with two SLC6A4 polymorphisms, 5-HTT gene-linked polymorphic region (HTTLPR) in the promoter and intron 2 variable number of tandem repeats (VNTR), in a sample of 105 ASD patients, their parents, and 52 control children. Quantitative transmission disequilibrium test (QTDT) results showed a significant effect on 5-HT levels of each SLC6A4 marker (P=0.017 for HTTLPR; P=0.047 for intron 2 VNTR) and of haplotypes of the two markers (P=0.017), with a major contribution of the L.Stin2.10 haplotype (P=0.0013). A 5-HT mean value in the range of hyperserotonemia was associated with the homozygous L.Stin2.10 haplotype (H (1,N=97)=7.76, P=0.0054), which occurred in 33% of hyperserotonemic patients against 6% of patients with normal 5-HT levels (Fisher's exact test: P=0.013, OR=8). Allele interaction at the HTTLPR locus was found, with a significant dominance variance effect on 5-HT levels. We found no transmission disequilibrium of any of the SLC6A4 variants in ASD. Our results show that the SLC6A4 gene is a significant factor in the determination of 5-HT levels, and that specific SLC6A4 variants are associated with an increased risk for hyperserotonemia in our sample of autistic patients. The biological mechanism, however, is unlikely to involve the SLC6A4 gene solely. The associated SLC6A4 alleles likely interact with other genes or environmental factors to produce the abnormally high 5-HT levels observed in this subset of autistic patients, who possibly represent a separate etiological group.",
+ "publisher": "Neurology",
+ "issn": "0028-3878",
+ "date": "1994-11-01",
+ "abstract": "There is a widely held belief that most patients presenting with senile chorea have late-onset Huntington's disease (HD) with an unknown family history. We measured CAG trinucleotide repeat expansion in the HD gene in four patients with a clinical presentation of senile chorea and found that CAG repetition lengths were normal. These findings support senile chorea as being a distinct clinical entity that is nosologically separate from late-onset HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15094787"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7969980"
},
{
- "id": "pmid:15076735",
+ "id": "pmid:7959696",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/15076735",
- "title": "Pseudo-neglect in Huntington's disease correlates with decreased angular gyrus density.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/7959696",
+ "title": "Trinucleotide (CAG) repeat expansion in chromosomes of Spanish patients with Huntington's disease.",
"type": "article-journal",
- "doi": "10.1097/00001756-200404290-00026",
+ "doi": "10.1007/bf00211028",
"authors": [
- ["Aileen K", "Ho"],
- ["Peter J", "Nestor"],
- ["Guy B", "Williams"],
- ["John L", "Bradshaw"],
- ["Barbara J", "Sahakian"],
- ["Trevor W", "Robbins"],
- ["Roger A", "Barker"]
+ ["J", "Benitez"],
+ ["E", "Fernandez"],
+ ["P", "Garcia Ruiz"],
+ ["M", "Robledo"],
+ ["C", "Ramos"],
+ ["J", "Y\u00e9benes"]
],
- "publisher": "Neuroreport",
- "issn": "0959-4965",
- "date": "2004-04-29",
- "abstract": "Visuospatial attentional bias was examined in Huntington's disease (HD) patients with mild disease, asymptomatic gene-positive patients and controls. No group differences were found on the grey scales task (which is a non-motor task of visuospatial attentional bias), although patients' trinucleotide (CAG) repeat length correlated with increasing leftward bias. On the line bisection task, symptomatic patients made significantly larger leftward bisection errors relative to controls, who showed the normal slight degree of leftward error (pseudo-neglect). The asymptomatic group showed a trend for greater leftward error than controls. A subset of participants went on to have structural MRI, which showed a correlation between increased leftward error on the line bisection task and reduced density in the angular gyrus area (BA39) bilaterally. This finding is consistent with recent literature suggesting a critical role for the angular gyrus in the lateralization of visuospatial attention.",
+ "publisher": "Human genetics",
+ "issn": "0340-6717",
+ "date": "1994-11-01",
+ "abstract": "Huntington's disease (HD) is a neurodegenerative and hereditary disease characterized by progressive movement disorders and mental and behavioral abnormalities. The HD gene is an expanding and unstable trinucleotide repeat (CAG repeat sequences). We studied 77 individuals from 38 families with HD in an attempt to obtain information for genetic counselling and differential diagnosis. Our results indicate that individuals with more than 40 repeats will be affected by the disease, whereas those with fewer than 30 will be healthy. There can be some overlap between 30 and 40 repeats, and one should be careful when interpreting these results.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15076735"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7959696"
},
{
- "id": "pmid:14993615",
+ "id": "pmid:7815437",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/14993615",
- "title": "Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/7815437",
+ "title": "Study of the Huntington's disease (HD) gene CAG repeats in schizophrenic patients shows overlap of the normal and HD affected ranges but absence of correlation with schizophrenia.",
"type": "article-journal",
- "doi": "10.1073/pnas.0308679101",
+ "doi": "10.1136/jmg.31.9.690",
"authors": [
- ["Nancy S", "Wexler"],
- ["Judith", "Lorimer"],
- ["Julie", "Porter"],
- ["Fidela", "Gomez"],
- ["Carol", "Moskowitz"],
- ["Edith", "Shackell"],
- ["Karen", "Marder"],
- ["Graciela", "Penchaszadeh"],
- ["Simone A", "Roberts"],
- ["Javier", "Gay\u00e1n"],
- ["Denise", "Brocklebank"],
- ["Stacey S", "Cherny"],
- ["Lon R", "Cardon"],
- ["Jacqueline", "Gray"],
- ["Stephen R", "Dlouhy"],
- ["Sandra", "Wiktorski"],
- ["Marion E", "Hodes"],
- ["P Michael", "Conneally"],
- ["Jack B", "Penney"],
- ["James", "Gusella"],
- ["Jang-Ho", "Cha"],
- ["Michael", "Irizarry"],
- ["Diana", "Rosas"],
- ["Steven", "Hersch"],
- ["Zane", "Hollingsworth"],
- ["Marcy", "MacDonald"],
- ["Anne B", "Young"],
- ["J Michael", "Andresen"],
- ["David E", "Housman"],
- ["Margot Mieja", "De Young"],
- ["Ernesto", "Bonilla"],
- ["Theresa", "Stillings"],
- ["Americo", "Negrette"],
- ["S Robert", "Snodgrass"],
- ["Maria Dolores", "Martinez-Jaurrieta"],
- ["Maria A", "Ramos-Arroyo"],
- ["Jacqueline", "Bickham"],
- ["Juan Sanchez", "Ramos"],
- ["Frederick", "Marshall"],
- ["Ira", "Shoulson"],
- ["Gustavo J", "Rey"],
- ["Andrew", "Feigin"],
- ["Norman", "Arnheim"],
- ["Amarilis", "Acevedo-Cruz"],
- ["Leticia", "Acosta"],
- ["Jose", "Alvir"],
- ["Kenneth", "Fischbeck"],
- ["Leslie M", "Thompson"],
- ["Angela", "Young"],
- ["Leon", "Dure"],
- ["Christopher J", "O'Brien"],
- ["Jane", "Paulsen"],
- ["Adam", "Brickman"],
- ["Denise", "Krch"],
- ["Shelley", "Peery"],
- ["Penelope", "Hogarth"],
- ["Donald S", "Higgins"],
- ["Bernhard", "Landwehrmeyer"]
+ ["D C", "Rubinsztein"],
+ ["J", "Leggo"],
+ ["S", "Goodburn"],
+ ["T J", "Crow"],
+ ["R", "Lofthouse"],
+ ["L E", "DeLisi"],
+ ["D E", "Barton"],
+ ["M A", "Ferguson-Smith"]
],
- "publisher": "Proceedings of the National Academy of Sciences of the United States of America",
- "issn": "0027-8424",
- "date": "2004-03-01",
- "abstract": "Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a triplet (CAG) expansion mutation. The length of the triplet repeat is the most important factor in determining age of onset of HD, although substantial variability remains after controlling for repeat length. The Venezuelan HD kindreds encompass 18,149 individuals spanning 10 generations, 15,409 of whom are living. Of the 4,384 immortalized lymphocyte lines collected, 3,989 DNAs were genotyped for their HD alleles, representing a subset of the population at greatest genetic risk. There are 938 heterozygotes, 80 people with variably penetrant alleles, and 18 homozygotes. Analysis of the 83 kindreds that comprise the Venezuelan HD kindreds demonstrates that residual variability in age of onset has both genetic and environmental components. We created a residual age of onset phenotype from a regression analysis of the log of age of onset on repeat length. Familial correlations (correlation +/- SE) were estimated for sibling (0.40 +/- 0.09), parent-offspring (0.10 +/- 0.11), avuncular (0.07 +/- 0.11), and cousin (0.15 +/- 0.10) pairs, suggesting a familial origin for the residual variance in onset. By using a variance-components approach with all available familial relationships, the additive genetic heritability of this residual age of onset trait is 38%. A model, including shared sibling environmental effects, estimated the components of additive genetic (0.37), shared environment (0.22), and nonshared environment (0.41) variances, confirming that approximately 40% of the variance remaining in onset age is attributable to genes other than the HD gene and 60% is environmental.",
+ "publisher": "Journal of medical genetics",
+ "issn": "0022-2593",
+ "date": "1994-09-01",
+ "abstract": "The CAG repeats in the Huntington's disease gene were investigated in chromosomes from 71 unrelated schizophrenic persons and 18 patients with schizoaffective disorder in order to determine if any of these patients had abnormal expansions. All of the probands had repeat sizes in the normal range (< 35 repeats) and there was no significant difference between the allele distributions of these patients and the normal controls. The families of two patients with 32 repeats and one patient with 34 repeats were investigated further and showed no uniform segregation of the disease with the large repeat alleles. The proband with 34 repeats inherited a chromosome that originally had 36 repeats in her father. The presence of 36 CAG repeats in members of her family and in HD patients suggests that there is an overlap between the normal and Huntington's disease CAG repeat size ranges. The more recently described CCG polymorphism in this gene was also examined in the schizophrenic and schizoaffective persons. All patients had alleles in the normal range.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:14993615"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7815437"
},
{
- "id": "pmid:14713958",
+ "id": "pmid:8208412",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/14713958",
- "title": "Specific caspase interactions and amplification are involved in selective neuronal vulnerability in Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/8208412",
+ "title": "CAG repeat size and clinical presentation in Huntington's disease.",
"type": "article-journal",
- "doi": "10.1038/sj.cdd.4401358",
+ "doi": "10.1212/wnl.44.6.1137",
"authors": [
- ["E", "Hermel"],
- ["J", "Gafni"],
- ["S S", "Propp"],
- ["B R", "Leavitt"],
- ["C L", "Wellington"],
- ["J E", "Young"],
- ["A S", "Hackam"],
- ["A V", "Logvinova"],
- ["A L", "Peel"],
- ["S F", "Chen"],
- ["V", "Hook"],
- ["R", "Singaraja"],
- ["S", "Krajewski"],
- ["P C", "Goldsmith"],
- ["H M", "Ellerby"],
- ["M R", "Hayden"],
- ["D E", "Bredesen"],
- ["L M", "Ellerby"]
+ ["T", "Ashizawa"],
+ ["L J", "Wong"],
+ ["C S", "Richards"],
+ ["C T", "Caskey"],
+ ["J", "Jankovic"]
],
- "publisher": "Cell death and differentiation",
- "issn": "1350-9047",
- "date": "2004-04-01",
- "abstract": "Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder resulting in selective neuronal loss and dysfunction in the striatum and cortex. The molecular pathways leading to the selectivity of neuronal cell death in HD are poorly understood. Proteolytic processing of full-length mutant huntingtin (Htt) and subsequent events may play an important role in the selective neuronal cell death found in this disease. Despite the identification of Htt as a substrate for caspases, it is not known which caspase(s) cleaves Htt in vivo or whether regional expression of caspases contribute to selective neuronal cells loss. Here, we evaluate whether specific caspases are involved in cell death induced by mutant Htt and if this correlates with our recent finding that Htt is cleaved in vivo at the caspase consensus site 552. We find that caspase-2 cleaves Htt selectively at amino acid 552. Further, Htt recruits caspase-2 into an apoptosome-like complex. Binding of caspase-2 to Htt is polyglutamine repeat-length dependent, and therefore may serve as a critical initiation step in HD cell death. This hypothesis is supported by the requirement of caspase-2 for the death of mouse primary striatal cells derived from HD transgenic mice expressing full-length Htt (YAC72). Expression of catalytically inactive (dominant-negative) forms of caspase-2, caspase-7, and to some extent caspase-6, reduced the cell death of YAC72 primary striatal cells, while the catalytically inactive forms of caspase-3, -8, and -9 did not. Histological analysis of post-mortem human brain tissue and YAC72 mice revealed activation of caspases and enhanced caspase-2 immunoreactivity in medium spiny neurons of the striatum and the cortical projection neurons when compared to controls. Further, upregulation of caspase-2 correlates directly with decreased levels of brain-derived neurotrophic factor in the cortex and striatum of 3-month YAC72 transgenic mice and therefore suggests that these changes are early events in HD pathogenesis. These data support the involvement of caspase-2 in the selective neuronal cell death associated with HD in the striatum and cortex.",
+ "publisher": "Neurology",
+ "issn": "0028-3878",
+ "date": "1994-06-01",
+ "abstract": "The specific mutation in Huntington's disease (HD) is an expansion of the unstable CAG trinucleotide repeat in the IT15 gene in chromosome 4p. We examined the relationship between the CAG repeat size and clinical presentation in 36 patients with suspected diagnosis of HD. Twelve patients had no relatives with documented HD, and five of them failed to show the expanded (>37) CAG repeats. The remaining 31 patients, including seven patients with atypical clinical features for HD (three without and four with family history of documented HD), were heterozygotes for the CAG repeat expansion. There were large CAG repeats (50 copies) in paternally transmitted HD cases with early onset (age 30 or earlier). The rate of disease progression was faster in paternally transmitted cases regardless of the CAG repeat length or age of onset. We conclude that (1) patients lacking the family history of HD frequently show no expansion of the CAG repeats, and (2) the sex of the affected parent influences both the CAG repeat size and the phenotypic expression of the HD gene in the offspring.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:14713958"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8208412"
},
{
- "id": "pmid:14708029",
+ "id": "pmid:8178825",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/14708029",
- "title": "Serotonin transporter gene and autism: a haplotype analysis in an Irish autistic population.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/8178825",
+ "title": "Huntington disease without CAG expansion: phenocopies or errors in assignment?",
"type": "article-journal",
- "doi": "10.1038/sj.mp.4001459",
+ "doi": "",
"authors": [
- ["J", "Conroy"],
- ["E", "Meally"],
- ["G", "Kearney"],
- ["M", "Fitzgerald"],
- ["M", "Gill"],
- ["L", "Gallagher"]
+ ["S E", "Andrew"],
+ ["Y P", "Goldberg"],
+ ["B", "Kremer"],
+ ["F", "Squitieri"],
+ ["J", "Theilmann"],
+ ["J", "Zeisler"],
+ ["H", "Telenius"],
+ ["S", "Adam"],
+ ["E", "Almquist"],
+ ["M", "Anvret"]
],
- "publisher": "Molecular psychiatry",
- "issn": "1359-4184",
- "date": "2004-06-01",
- "abstract": "The role of the serotonin transporter (5-HTT) in the development of neuropsychiatric disorders has been widely investigated. Two polymorphisms, an insertion/deletion in the promoter region and a 12 repeat allele in a variable nucleotide tandem repeat (VNTR) in intron 2, drive higher expression of the 5-HTT gene. Four studies have shown nominally significant excess transmission of alleles of the 5-HTT gene in autism, while three studies have reported no excess transmission. This present study investigates the role of 5-HTT in the genetically homogenous Irish population. In all, 84 families were genotyped for five polymorphisms (three SNPs, a VNTR and an in/del). The analysis of allele transmissions using the transmission disequilibrium test (TDT) was undertaken and indicated preferential transmission of the short promoter allele (TDT P-value=0.0334). Linkage disequilibrium between markers was calculated and haplotypes were assessed for excess transmission and odds ratios (ORs) to affected children. A number of haplotypes, especially those involving and surrounding SNP10, showed evidence of association. The ORs ranged from 1.2 to 2.4. The most significant haplotype associated with transmission to affected probands was the SNP10-VNTR-SNP18 haplotype (chi(2)=7.3023, P=0.0069, odds ratio=1.8). This haplotype included the 12 repeat allele of the VNTR, which is associated with increased expression and may play a subtle role in the early development of the brain in affected probands.",
+ "publisher": "American journal of human genetics",
+ "issn": "0002-9297",
+ "date": "1994-05-01",
+ "abstract": "Huntington disease (HD) has been shown to be associated with an expanded CAG repeat within a novel gene on 4p16.3 (IT15). A total of 30 of 1,022 affected persons (2.9% of our cohort) did not have an expanded CAG in the disease range. The reasons for not observing expansion in affected individuals are important for determining the sensitivity of using repeat length both for diagnosis of affected patients and for predictive testing programs and may have biological relevance for the understanding of the molecular mechanism underlying HD. Here we show that the majority (18) of the individuals with normal sized alleles represent misdiagnosis, sample mix-up, or clerical error. The remaining 12 patients represent possible phenocopies for HD. In at least four cases, family studies of these phenocopies excluded 4p16.3 as the region responsible for the phenotype. Mutations in the HD gene that are other than CAG expansion have not been excluded for the remaining eight cases; however, in as many as seven of these persons, retrospective review of these patients' clinical features identified characteristics not typical for HD. This study shows that on rare occasions mutations in other, as-yet-undefined genes can present with a clinical phenotype very similar to that of HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:14708029"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8178825"
},
{
- "id": "pmid:14625025",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/14625025",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:14625025']' timed out after 3 seconds"
+ "id": "pmid:8044653",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/8044653",
+ "title": "Limited expansion of the (CAG)n repeat of the Huntington gene: a premutation (?).",
+ "type": "article-journal",
+ "doi": "10.1159/000472340",
+ "authors": [
+ ["E", "Legius"],
+ ["H", "Cuppens"],
+ ["H", "Dierick"],
+ ["K", "Van Zandt"],
+ ["R", "Dom"],
+ ["J P", "Fryns"],
+ ["G", "Evers-Kiebooms"],
+ ["M", "Decruyenaere"],
+ ["K", "Demyttenaere"],
+ ["P", "Marynen"]
+ ],
+ "publisher": "European journal of human genetics : EJHG",
+ "issn": "1018-4813",
+ "date": "1994-01-01",
+ "abstract": "Huntington's disease (HD) is an autosomal dominant disorder with choreic movements, psychiatric manifestations and cognitive dysfunction. Recently the IT15 gene on chromosome 4p has been identified containing an unstable and expanded trinucleotide repeat in patients with HD. We report on the characteristics of this repeat in 248 individuals from 41 Belgian HD families. The length of the expanded repeat was defined precisely and reproducibly on an ALF sequencer and correlated well with the age of onset (r = -0.72). Paternal transmission of the expanded repeat resulted on average in a significantly longer repeat length (+2.79 repeats) than maternal transmission (-0.29 repeats). (CAG)n repeat of a premutation (?) size was observed in this population with subsequent expansion in the disease range. Presymptomatic or prenatal testing using only linked markers may be problematic in these cases.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8044653"
},
{
- "id": "pmid:14581669",
+ "id": "pmid:7888133",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/14581669",
- "title": "Huntington's disease: clinical correlates of disability and progression.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/7888133",
+ "title": "Trinucleotide repeat elongation in the huntingtin gene in Huntington's disease patients from 85 French families. The French HD Research Group.",
"type": "article-journal",
- "doi": "10.1212/01.wnl.0000086373.32347.16",
+ "doi": "",
"authors": [
- ["N", "Mahant"],
- ["E A", "McCusker"],
- ["K", "Byth"],
- ["S", "Graham"]
+ ["G", "Lucotte"],
+ ["A", "Aouiz\u00e9rate"],
+ ["O", "Loreille"],
+ ["N", "G\u00e9rard"],
+ ["J C", "Turpin"]
],
- "publisher": "Neurology",
- "issn": "1526-632X",
- "date": "2003-10-28",
- "abstract": "To define the phenotypic variation in a large population of patients with Huntington disease (HD) and to identity clinical features that predict disability and the rate of disease progression.",
+ "publisher": "Genetic counseling (Geneva, Switzerland)",
+ "issn": "1015-8146",
+ "date": "1994-01-01",
+ "abstract": "IT15 is a new gene encoding a protein named huntingtin; a polymorphic CAG repeat in the proposed open reading frame of IT15 has been characterized, and an elongation of this repeat has been correlated to Huntington's disease (HD). We have investigated the CAG repeat in the huntingtin gene in 85 unrelated French families with Huntington's disease. In 79 patients (from 60 families, where at least one HD DNA was available) we found repeat lengths of 37 to 100 units, in contrast to 11 to 35 CAG's on normal chromosomes. Comparison of repeat length and age at onset of disease symptoms in 71 individuals confirms an inverse correlation (r = -0.51 for p < 10(-4)) between the age at onset and the number of CAG repeat units.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:14581669"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7888133"
},
{
- "id": "pmid:14570710",
+ "id": "pmid:8133508",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/14570710",
- "title": "Dramatic tissue-specific mutation length increases are an early molecular event in Huntington disease pathogenesis.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/8133508",
+ "title": "Gametic but not somatic instability of CAG repeat length in Huntington's disease.",
"type": "article-journal",
- "doi": "10.1093/hmg/ddg352",
+ "doi": "10.1136/jmg.30.12.982",
"authors": [
- ["Laura", "Kennedy"],
- ["Elizabeth", "Evans"],
- ["Chiung-Mei", "Chen"],
- ["Lyndsey", "Craven"],
- ["Peter J", "Detloff"],
- ["Margaret", "Ennis"],
- ["Peggy F", "Shelbourne"]
+ ["M E", "MacDonald"],
+ ["G", "Barnes"],
+ ["J", "Srinidhi"],
+ ["M P", "Duyao"],
+ ["C M", "Ambrose"],
+ ["R H", "Myers"],
+ ["J", "Gray"],
+ ["P M", "Conneally"],
+ ["A", "Young"],
+ ["J", "Penney"]
],
- "publisher": "Human molecular genetics",
- "issn": "0964-6906",
- "date": "2003-10-21",
- "abstract": "Huntington disease is caused by the expansion of a CAG repeat encoding an extended glutamine tract in a protein called huntingtin. Although the mutant protein is widely expressed, the earliest and most striking neuropathological changes are observed in the striatum. Here we show dramatic mutation length increases (gains of up to 1000 CAG repeats) in human striatal cells early in the disease course, most likely before the onset of pathological cell loss. Studies of knock-in HD mouse models indicate that the size of the initial CAG repeat mutation may influence both onset and tissue-specific patterns of age-dependent, expansion-biased mutation length variability. Given that CAG repeat length strongly correlates with clinical severity, we suggest that somatic increases of mutation length may play a major role in the progressive nature and cell-selective aspects of both adult-onset and juvenile-onset HD pathogenesis and we discuss the implications of this interpretation of the data presented.",
+ "publisher": "Journal of medical genetics",
+ "issn": "0022-2593",
+ "date": "1993-12-01",
+ "abstract": "Instability of a CAG repeat in 4p16.3 has been found in Huntington's disease (HD) chromosomes. Unlike a similar repeat in the fragile X syndrome, the expanded HD repeat showed no evidence of somatic instability in a comparison of blood, lymphoblast, and brain DNA from the same persons. Four pairs of monozygotic HD twins displayed identical CAG repeat lengths suggesting that repeat size is determined in gametogenesis. In contrast with the fragile X syndrome and with HD somatic tissue, mosaicism was readily detected as a diffuse spread of repeat lengths in DNA from HD sperm samples. Typically, the modal repeat size was larger in the sperm DNA than in corresponding lymphoblast DNA, with the greatest degree of gametic mosaicism coinciding with the longest somatic CAG repeats. These data indicate that the developmental timing of repeat instability appears to differ between HD and fragile X syndrome, and that the fundamental mechanisms leading to repeat expansion may therefore be distinct.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:14570710"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8133508"
},
{
- "id": "pmid:12886033",
+ "id": "pmid:8133495",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/12886033",
- "title": "Association study of serotonin transporter gene VNTR polymorphism and mood disorders, onset age and suicide attempts in a Chinese sample.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/8133495",
+ "title": "A study of the Huntington's disease associated trinucleotide repeat in the Scottish population.",
"type": "article-journal",
- "doi": "10.1159/000071821",
+ "doi": "10.1136/jmg.30.12.1003",
"authors": [
- ["Feng-Chang", "Yen"],
- ["Chen-Jee", "Hong"],
- ["Sheu-Jane", "Hou"],
- ["Jiunn-Kae", "Wang"],
- ["Shih-Jen", "Tsai"]
+ ["L H", "Barron"],
+ ["J P", "Warner"],
+ ["M", "Porteous"],
+ ["S", "Holloway"],
+ ["S", "Simpson"],
+ ["R", "Davidson"],
+ ["D J", "Brock"]
],
- "publisher": "Neuropsychobiology",
- "issn": "0302-282X",
- "date": "2003-01-01",
- "abstract": "The human serotonin transporter (5-HTT) gene is an important candidate for the pathogenesis of mood disorders. Associations have been reported between a variable-number tandem-repeat polymorphism in intron 2 of the serotonin transporter gene (5-HTTVNTR) and mood disorders in a number of studies of Western and Chinese populations. However, no such relationships have been determined in other analogous research. To replicate these positive findings in a Chinese population and to determine the association between onset age of bipolar disorder and 5-HTTVNTR, we investigated the prevalence of this polymorphism in an independent Chinese population (83 bipolar disorder patients, 77 major depressive disorder patients and 169 controls), demonstrating no significant association between the 5-HTTVNTR polymorphism and mood disorders or age at onset. Further, no association was demonstrated between this polymorphism and suicidal history in mood disorder patients. These negative findings suggest that 5-HTTVNTR does not play a major role in the pathogenesis of mood disorder in Chinese populations.",
+ "publisher": "Journal of medical genetics",
+ "issn": "0022-2593",
+ "date": "1993-12-01",
+ "abstract": "Accurate measurements of a specific CAG repeat sequence in the Huntington's disease (HD) gene in 337 HD patients and 229 normal controls from the Scottish population showed a range from 35 to 62 repeats in affected subjects and eight to 33 in normal subjects. A link between early onset of symptoms and very high repeat number was seen. For HD patients with the most common affected allele sizes (39 to 42 repeats) absolute repeat size was a poor index for the age at onset of symptoms. There was variability in the transmitted repeat size for both sexes in the HD size range. We observed a significant increase of repeat size for paternal transmission of the disease and greater instability for paternally transmitted CAG repeats in the HD size range.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12886033"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8133495"
},
{
- "id": "pmid:12850791",
+ "id": "pmid:8111374",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/12850791",
- "title": "Expansion of EBV latent membrane protein 2a specific cytotoxic T cells for the adoptive immunotherapy of EBV latency type 2 malignancies: influence of recombinant IL12 and IL15.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/8111374",
+ "title": "Mitotic stability and meiotic variability of the (CAG)n repeat in the Huntington disease gene.",
"type": "article-journal",
- "doi": "10.1080/14653240310001262",
+ "doi": "10.1093/hmg/2.12.2063",
"authors": [
- ["H-J", "Wagner"],
- ["U", "Sili"],
- ["B", "Gahn"],
- ["S", "Vigouroux"],
- ["M H", "Huls"],
- ["W", "Xie"],
- ["D", "Vignali"],
- ["M K", "Brenner"],
- ["H E", "Heslop"],
- ["C M", "Rooney"]
+ ["C", "Z\u00fchlke"],
+ ["O", "Riess"],
+ ["B", "Bockel"],
+ ["H", "Lange"],
+ ["U", "Thies"]
],
- "publisher": "Cytotherapy",
- "issn": "1465-3249",
- "date": "2003-01-01",
- "abstract": "EBV-associated malignancies with a Type II latency gene expression pattern, such as EBV-positive HD, or nasopharyngeal carcinoma, frequently express the EBV latency Ag LMP2a. Hence, they provide a potential target for adoptive immunotherapy using in vitro-generated LMP2a-specific cytotoxic T lymphocytes (CTL). In this study, LMP2a-specific CTL were specifically amplified and the influence of rIL12 and rIL15 on the culture outcome was tested.",
+ "publisher": "Human molecular genetics",
+ "issn": "0964-6906",
+ "date": "1993-12-01",
+ "abstract": "The gene causing Huntington's disease, an autosomal dominantly inherited, neurodegenerative disorder, has been identified recently. The corresponding mutation is involving an expansion in the number of (CAG)n repeats in the coding region of the Huntington's disease gene on chromosome 4. In this report, we demonstrate the length variation of the repeat in 513 non-HD chromosomes from normal individuals and HD patients showing 23 alleles with 11 to 33 repeats. Analyzing the inheritance of the (CAG)n stretch we found meiotic instability for HD alleles ([CAG]40 to [CAG]75) with a mutation frequency of approximately 0.7, while in 431 meioses of normal alleles only two expansions were identified. The risk of expansion during spermatogenesis is enhanced compared to oogenesis explaining juvenile onset by transmission from affected fathers. Further, the number of (CAG)n copies in an affected individual in relation to the sex of the transmitting parent was evaluated and no significant differences were found. No mosaicism or differences in the repeat lengths were observed in the DNA from different tissues including brain and lymphocytes of two HD patients indicating mitotic stability of the mutation. Therefore, the determination of the repeat number in the DNA of blood lymphocytes is probably representative of all tissues in a patient.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12850791"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8111374"
},
{
- "id": "pmid:12824708",
+ "id": "pmid:8252042",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/12824708",
- "title": "DNA testing for Huntington disease in the Turkish population.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/8252042",
+ "title": "De novo expansion of a (CAG)n repeat in sporadic Huntington's disease.",
"type": "article-journal",
- "doi": "10.1159/000070854",
+ "doi": "10.1038/ng1093-168",
"authors": [
- ["Fahri", "Akbas"],
- ["Nihan", "Erginel-Unaltuna"]
+ ["R H", "Myers"],
+ ["M E", "MacDonald"],
+ ["W J", "Koroshetz"],
+ ["M P", "Duyao"],
+ ["C M", "Ambrose"],
+ ["S A", "Taylor"],
+ ["G", "Barnes"],
+ ["J", "Srinidhi"],
+ ["C S", "Lin"],
+ ["W L", "Whaley"]
],
- "publisher": "European neurology",
- "issn": "0014-3022",
- "date": "2003-01-01",
- "abstract": "Huntington disease (HD) is an autosomal dominant inherited disease, characterized by involuntary movements, behavioral and personality changes and dementia. Although the mean age at onset is about 40 years, onset varies from 5 to 79 years. Therefore, at-risk individuals are never sure to have escaped the disease. The genetic defect is a CAG trinucleotide repeat expansion at the 5' end of the IT-15 gene on chromosome 4. In this study, we analyzed 127 patients with HD and 122 healthy controls. The numbers of CAG repeats varied from 38 to 78 (median: 42) in 127 HD patients, while in healthy controls we observed only 10-35 CAG repeats (median: 18). The length of the CAG repeat expansion in Turkish HD patients and normal controls was similar to that reported from other populations. Negative correlations (r = -0.67) were also found between age of disease onset and repeat length.",
+ "publisher": "Nature genetics",
+ "issn": "1061-4036",
+ "date": "1993-10-01",
+ "abstract": "Huntington's disease (HD) chromosomes contain an expanded unstable (CAG)n repeat in chromosome 4p16.3. We have examined nine families with potential de novo expression of the disease. With one exception, all of the affected individuals had 42 or more repeat units, well above the normal range. In four families, elderly unaffected relatives inherited the same chromosome as that containing the expanded repeat in the proband, but had repeat lengths of 34-38 units, spanning the gap between the normal and HD distributions. Thus, mutation to HD is usually associated with an expansion from an already large repeat.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12824708"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8252042"
},
{
- "id": "pmid:12782968",
+ "id": "pmid:8242074",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/12782968",
- "title": "No evidence of association of two 5HT transporter gene polymorphisms and attention deficit hyperactivity disorder.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/8242074",
+ "title": "Trinucleotide repeat elongation in the Huntingtin gene in Huntington disease patients from 71 Danish families.",
"type": "article-journal",
- "doi": "10.1097/01.ypg.0000056177.32550.a5",
+ "doi": "10.1093/hmg/2.9.1475",
"authors": [
- ["Kate", "Langley"],
- ["Antony", "Payton"],
- ["Marian L", "Hamshere"],
- ["Helen M", "Pay"],
- ["Deborah C", "Lawson"],
- ["Darko", "Turic"],
- ["William", "Ollier"],
- ["Jane", "Worthington"],
- ["Michael J", "Owen"],
- ["Michael C", "O'Donovan"],
- ["Anita", "Thapar"]
+ ["A", "N\u00f8rrem\u00f8lle"],
+ ["O", "Riess"],
+ ["J T", "Epplen"],
+ ["K", "Fenger"],
+ ["L", "Hasholt"],
+ ["S A", "S\u00f8rensen"]
],
- "publisher": "Psychiatric genetics",
- "issn": "0955-8829",
- "date": "2003-06-01",
- "abstract": "Three studies to date have found evidence (or a trend for evidence) of linkage and association between the long allele of the 44 base pair repeat insertion/deletion 5-HTT functional polymorphism (5-HTTLPR) and attention deficit hyperactivity disorder (ADHD). In an attempt to replicate these findings, we examined this polymorphism and a variable number tandem repeat in the second intron of 5-HTT for association with ADHD.",
+ "publisher": "Human molecular genetics",
+ "issn": "0964-6906",
+ "date": "1993-09-01",
+ "abstract": "IT15 is a novel gene, localized to chromosome 4, and encoding a protein named Huntingtin. A polymorphic CAG repeat in the proposed open reading frame of IT15 has been characterized, and an elongation of this repeat has been correlated to Huntington's Disease. We have investigated the CAG repeat in the Huntingtin gene in 71 unrelated Danish patients with Huntington's Disease, and found repeat lengths of 39 to 70 repeat units in contrast to 9 to 30 CAG's on normal chromosomes. Comparison of repeat length and age at onset of disease symptoms in 52 individuals indicates an inverse correlation between the age at onset and the number of CAG repeat units.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12782968"
-},
-{
- "id": "pmid:12700167",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/12700167",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:12700167']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8242074"
},
{
- "id": "pmid:12599191",
+ "id": "pmid:2971929",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/12599191",
- "title": "Sudden infant death syndrome: association with a promoter polymorphism of the serotonin transporter gene.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/2971929",
+ "title": "Construction of a NotI linking library and isolation of new markers close to the Huntington's disease gene.",
"type": "article-journal",
- "doi": "10.1002/ajmg.a.20005",
+ "doi": "10.1093/nar/16.19.9185",
"authors": [
- ["Debra E", "Weese-Mayer"],
- ["Elizabeth M", "Berry-Kravis"],
- ["Brion S", "Maher"],
- ["Jean M", "Silvestri"],
- ["Mark E", "Curran"],
- ["Mary L", "Marazita"]
+ ["T M", "Pohl"],
+ ["M", "Zimmer"],
+ ["M E", "MacDonald"],
+ ["B", "Smith"],
+ ["M", "Bucan"],
+ ["A", "Poustka"],
+ ["S", "Volinia"],
+ ["S", "Searle"],
+ ["G", "Zehetner"],
+ ["J J", "Wasmuth"]
],
- "publisher": "American journal of medical genetics. Part A",
- "issn": "1552-4825",
- "date": "2003-03-15",
- "abstract": "Serotonergic receptor binding in the arcuate nucleus, n. raph\u00e9 obscurus, and other medullary regions is decreased in sudden infant death syndrome (SIDS) cases. Further, a variable tandem repeat sequence polymorphism in the promoter region of the serotonin transporter protein (5-HTT) gene has recently been associated with risk of SIDS in a Japanese cohort. This polymorphism differentially regulates 5-HTT expression, with the long allele (L), the SIDS-associated allele, being a more effective promoter than the short allele (S). We therefore investigated the 5-HTT promoter polymorphism in a cohort of 87 SIDS cases (43 African American and 44 Caucasian) and gender/ethnicity-matched controls. Significant positive associations were found between SIDS and the 5-HTT genotype distribution (P = 0.022), specifically with the L/L genotype (P = 0.048), and between SIDS and the 5-HTT L allele (P = 0.005). There was also a significant negative association between SIDS and the S/S genotype (P = 0.011). The comparisons were repeated in the African American and Caucasian subgroups. The data patterns were consistent in the subgroups, i.e., the L/L genotype and L allele were increased in the cases, but not all subgroup comparisons were statistically significant. These results indicate a relationship between SIDS and the L allele of the 5-HTT gene in African Americans and Caucasians, and if confirmed, will provide an important tool for identifying at-risk individuals and estimating the risk of recurrence.",
+ "publisher": "Nucleic acids research",
+ "issn": "0305-1048",
+ "date": "1988-10-11",
+ "abstract": "Linking clones contain sequences flanking recognition sites for enzymes cutting rarely in mammalian DNA. They can be used to obtain and correlate both physical and genetic mapping information over subregions of mammalian chromosomes. We have constructed and used a NotI linking clone library representing unmethylated NotI sites from HHW693 DNA, a hamster hybrid cell line containing 4p15-4pter and a fragment of 5p as its only human chromosome contribution. Human clones were identified by hybridisation with a cloned human repeat sequence, and localised further to subregions of human chromosome 4p15-4pter using a panel of additional hybrids. Clones from the region distal to the DNA probes (D4S10, D4S43, D4S95) linked to the Huntington's disease mutation, were further analysed. Four markers close to the HD gene: D4S111, D4S113, D4S114 and clone 417 are described here. In addition to serving as markers in physical and genetic mapping experiments, these linking clones provide probes next to cleavable NotI sites, and can therefore be used to screen NotI based chromosome jumping libraries. They also provide indications for potential gene sequences, identifiable as evolutionarily conserved sequences.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12599191"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:2971929"
},
{
- "id": "pmid:12438470",
+ "id": "pmid:3131233",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/12438470",
- "title": "Unilateral transplantation of human primary fetal tissue in four patients with Huntington's disease: NEST-UK safety report ISRCTN no 36485475.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/3131233",
+ "title": "Absence of B-cell or T-cell clonal expansion in nodular, lymphocyte predominant Hodgkin's disease.",
"type": "article-journal",
- "doi": "10.1136/jnnp.73.6.678",
+ "doi": "10.1016/s0046-8177(88)80210-7",
"authors": [
- ["A E", "Rosser"],
- ["R A", "Barker"],
- ["T", "Harrower"],
- ["C", "Watts"],
- ["M", "Farrington"],
- ["A K", "Ho"],
- ["R M", "Burnstein"],
- ["D K", "Menon"],
- ["J H", "Gillard"],
- ["J", "Pickard"],
- ["S B", "Dunnett"]
+ ["M D", "Linden"],
+ ["A J", "Fishleder"],
+ ["W E", "Katzin"],
+ ["R R", "Tubbs"]
],
- "publisher": "Journal of neurology, neurosurgery, and psychiatry",
- "issn": "0022-3050",
- "date": "2002-12-01",
- "abstract": "Huntington's disease (HD) is an inherited autosomal dominant condition in which there is a CAG repeat expansion in the huntingtin gene of 36 or more. Patients display progressive motor, cognitive, and behavioural deterioration associated with progressive cell loss and atrophy in the striatum. Currently there are no disease modifying treatments and current symptomatic treatments are only partially effective in the early to moderate stages. Neural transplantation is effective in animal models of HD and offers a potential strategy for brain repair in patients. The authors report a safety study of unilateral transplantation of human fetal striatal tissue into the striatum of four patients with HD.",
+ "publisher": "Human pathology",
+ "issn": "0046-8177",
+ "date": "1988-05-01",
+ "abstract": "Recent studies based upon immunophenotypic data have provided strong evidence that nodular lymphocyte predominant Hodgkin's disease (NLPHD) represents an entity that is distinct from other subtypes of Hodgkin's disease (HD). In contract to other forms of HD, the predominance of B-lymphocytes in NLPHD has prompted the thesis that this lesion is actually an atypical B-cell hyperplasia or follicular center cell lymphoma. Three cases of NLPHD by restriction endonuclease analysis were studied in an attempt to identify a clonal B-cell or T-cell expansion in this disorder. DNA was extracted from these tumors and hybridized to probes for the immunoglobulin genes (C kappa, C lambda, JH) and the T-cell receptor beta chain gene. Gene rearrangements were not detectable in any of the cases. The results provide genotypic evidence that there is not a monoclonal or oligoclonal proliferation of small B-lymphocytes or T-lymphocytes in NLPHD. The possibility that the L&H Reed-Sternberg cells are monoclonal cannot be excluded because their small number is below the level of sensitivity of this technique.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12438470"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:3131233"
},
{
- "id": "pmid:12405543",
+ "id": "pmid:38948793",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/12405543",
- "title": "Neuropsychological manifestations of the genetic mutation for Huntington's disease in presymptomatic individuals.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38948793",
+ "title": "NMR structures of small molecules bound to a model of an RNA CUG repeat expansion.",
"type": "article-journal",
- "doi": "10.1017/s1355617702870060",
+ "doi": "10.1101/2024.06.21.600119",
"authors": [
- ["Jason", "Brandt"],
- ["Barnett", "Shpritz"],
- ["Ann Marie", "Codori"],
- ["Russell", "Margolis"],
- ["Adam", "Rosenblatt"]
+ ["Jonathan L", "Chen"],
+ ["Amirhossein", "Taghavi"],
+ ["Alexander J", "Frank"],
+ ["Matthew A", "Fountain"],
+ ["Shruti", "Choudhary"],
+ ["Soma", "Roy"],
+ ["Jessica L", "Childs-Disney"],
+ ["Matthew D", "Disney"]
],
- "publisher": "Journal of the International Neuropsychological Society : JINS",
- "issn": "1355-6177",
- "date": "2002-11-01",
- "abstract": "A triplet repeat (CAG) expansion mutation in the huntingtin gene on chromosome 4 is responsible for Huntington's disease (HD). Presymptomatic genetic testing for this mutation has identified clinically normal persons who are virtually certain to develop this dementing illness if they live a normal lifespan. The present study sought to determine whether these \"mutation-positive\" persons have impairments in cognitive functioning. Seventy-five mutation-positive persons did not differ from 128 mutation-negative persons on tests selected for their sensitivity to early-stage HD. Interestingly, however, those with the mutation viewed themselves as more likely to develop HD than did those without the mutation. Among mutation-positive subjects, having a longer CAG repeat mutation was likewise not associated with cognitive impairment. However, being closer to estimated disease onset (a product of repeat length and parent's age at onset) was associated with selected cognitive impairments. When viewed in light of previous studies showing atrophy of the caudate nucleus and putamen in mutation-carriers who are close to onset but not those far from onset, these results suggest that subtle changes in brain and behavior may be detected shortly before subjects with the HD mutation develop sufficient signs and symptoms for diagnosis. Conceptual and methodological problems associated with the search for presymptomatic cognitive and behavioral indicators of dementing illness are discussed.",
+ "publisher": "bioRxiv : the preprint server for biology",
+ "issn": "2692-8205",
+ "date": "2024-06-22",
+ "abstract": "Trinucleotide repeat expansions fold into long, stable hairpins and cause a variety of incurable RNA gain-of-function diseases such as Huntington's disease, the myotonic dystrophies, and spinocerebellar ataxias. One approach for treating these diseases is to bind small molecules to the structured RNAs. Both Huntington's disease-like 2 (HDL2) and myotonic dystrophy type 1 (DM1) are caused by a r(CUG) repeat expansion, or r(CUG)",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12405543"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38948793"
},
{
- "id": "pmid:12393802",
+ "id": "pmid:29208631",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/12393802",
- "title": "Aggregated polyglutamine peptides delivered to nuclei are toxic to mammalian cells.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/29208631",
+ "title": "The",
"type": "article-journal",
- "doi": "10.1093/hmg/11.23.2905",
+ "doi": "10.1242/dmm.029082",
"authors": [
- ["Wen", "Yang"],
- ["John R", "Dunlap"],
- ["Richard B", "Andrews"],
- ["Ronald", "Wetzel"]
+ ["Eduardo", "Calpena"],
+ ["V\u00edctor", "L\u00f3pez Del Amo"],
+ ["Mouli", "Chakraborty"],
+ ["Beatriz", "Llamus\u00ed"],
+ ["Rub\u00e9n", "Artero"],
+ ["Carmen", "Espin\u00f3s"],
+ ["M\u00e1ximo I", "Galindo"]
],
- "publisher": "Human molecular genetics",
- "issn": "0964-6906",
- "date": "2002-11-01",
- "abstract": "A number of observations point to the aggregation of expanded polyglutamine [poly(Q)]-containing proteins as playing a central role in the etiology of Huntington's disease (HD) and other expanded CAG-repeat diseases. Transfected cell and transgenic animal models provide some of this support, but irrefutable data on the cytotoxicity of poly(Q) aggregates is lacking. This may be due in part to difficulties in observing all aggregated states in these models, and in part to the inability to conclusively rule out the role of monomeric states of the poly(Q) protein. To address these questions, we produced aggregates of simple poly(Q) peptides in vitro and introduced them to mammalian cells in culture. We find that Cos-7 and PC-12 cells in culture readily take up aggregates of chemically synthesized poly(Q) peptides. Simple poly(Q) aggregates are localized to the cytoplasm and have little impact on cell viability. Aggregates of poly(Q) peptides containing a nuclear localization signal, however, are localized to nuclei and lead to dramatic cell death. Amyloid fibrils of a non-poly(Q) peptide are non-toxic, whether localized to the cytoplasm or nucleus. Nuclear localization of an aggregate of a short, Q(20), poly(Q) peptide is just as toxic as that of a long poly(Q) peptide, supporting the notion that the influence of poly(Q) repeat length on disease risk and age of onset is at the level of aggregation efficiency. The results support a direct role for poly(Q) aggregates in HD-related neurotoxicity.",
+ "publisher": "Disease models & mechanisms",
+ "issn": "1754-8411",
+ "date": "2018-01-17",
+ "abstract": "Members of the Junctophilin (JPH) protein family have emerged as key actors in all excitable cells, with crucial implications for human pathophysiology. In mammals, this family consists of four members (JPH1-JPH4) that are differentially expressed throughout excitable cells. The analysis of knockout mice lacking JPH subtypes has demonstrated their essential contribution to physiological functions in skeletal and cardiac muscles and in neurons. Moreover, mutations in the human",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12393802"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29208631"
},
{
- "id": "pmid:12221159",
+ "id": "pmid:22447335",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/12221159",
- "title": "Huntington's disease: a randomized, controlled trial using the NMDA-antagonist amantadine.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22447335",
+ "title": "JPH3 repeat expansions cause a progressive akinetic-rigid syndrome with severe dementia and putaminal rim in a five-generation African-American family.",
"type": "article-journal",
- "doi": "10.1212/wnl.59.5.694",
+ "doi": "10.1007/s10048-012-0318-9",
"authors": [
- ["L", "Verhagen Metman"],
- ["M J", "Morris"],
- ["C", "Farmer"],
- ["M", "Gillespie"],
- ["K", "Mosby"],
- ["J", "Wuu"],
- ["T N", "Chase"]
+ ["Susanne A", "Schneider"],
+ ["Kate E", "Marshall"],
+ ["Jianfeng", "Xiao"],
+ ["Mark S", "LeDoux"]
],
- "publisher": "Neurology",
- "issn": "0028-3878",
- "date": "2002-09-10",
- "abstract": "To examine the acute effects of the NMDA receptor antagonist amantadine on motor and cognitive function in Huntington's disease (HD).",
+ "publisher": "Neurogenetics",
+ "issn": "1364-6753",
+ "date": "2012-03-25",
+ "abstract": "We report the clinical, neuropsychological, genetic, and radiological features of a large five-generation African-American kindred from the southern USA presenting with a progressive akinetic-rigid syndrome and severe dementia, but clinically insignificant chorea, due to mutations in junctophillin 3 (JPH3). Overt disease onset was in the mid-20s to late 30s with cognitive decline, REM sleep disturbance, or psychiatric features, followed by development of a levodopa-unresponsive akinetic-rigid motor syndrome. Dystonia and myoclonus were present in some subjects. A bedridden, nonverbal severely akinetic-rigid state developed within 10 to 15 years after onset. CTG repeat expansions ranged from 47 to 53. Imaging revealed generalized cerebral atrophy with severe striatal involvement and putaminal rim hyperintensity. Analysis of our kindred indicates that JPH3 mutations should be considered in the differential diagnosis of early-onset dementia and hypokinetic-rigid syndromes in individuals of African descent. Moreover, chorea may not be overtly manifest at presentation or during significant parts of the disease course.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12221159"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22447335"
},
{
- "id": "pmid:12218657",
+ "id": "pmid:14557581",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/12218657",
- "title": "Major psychiatric disorders and the serotonin transporter gene (SLC6A4): family-based association studies.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/14557581",
+ "title": "Huntington's disease--like 2 can present as chorea-acanthocytosis.",
"type": "article-journal",
- "doi": "10.1097/00041444-200209000-00004",
+ "doi": "10.1212/01.wnl.0000085866.68470.6d",
"authors": [
- ["Albena", "Dimitrova"],
- ["Lyudmila", "Georgieva"],
- ["Ivan", "Nikolov"],
- ["Nadejda", "Poriazova"],
- ["Stefan", "Krastev"],
- ["Draga", "Toncheva"],
- ["Michael J", "Owen"],
- ["George", "Kirov"]
+ ["R H", "Walker"],
+ ["A", "Rasmussen"],
+ ["D", "Rudnicki"],
+ ["S E", "Holmes"],
+ ["E", "Alonso"],
+ ["T", "Matsuura"],
+ ["T", "Ashizawa"],
+ ["B", "Davidoff-Feldman"],
+ ["R L", "Margolis"]
],
- "publisher": "Psychiatric genetics",
- "issn": "0955-8829",
- "date": "2002-09-01",
- "abstract": "The serotonin transporter (5-HTT) is a suitable candidate gene to test for involvement in the pathogenesis of major psychiatric disorders. We used the method of family-based controls to test for association between disease and a variable number tandem repeat (VNTR) in intron 2 of the gene, which has received support for involvement in the pathogenesis of several psychiatric disorders. We analysed 413 proband-parent trios of Bulgarian origin: 266 had a schizophrenic proband, 103 had a bipolar proband and 44 had a schizoaffective proband. The results were analysed using the extended transmission disequilibrium test. Possible effects of different alleles on certain clinical variables were examined by correlation analysis. Three alleles were detected: STin2.9, STin2.10 and STin2.12. None of the three diagnostic samples showed preferential transmission of alleles that reached conventional levels of statistical significance. We could not confirm previous results that STin2.12 allele increases susceptibility to bipolar disorder type I. The rare STin2.9 showed a non-significant trend for preferential transmission in the sample as a whole: 18 transmitted versus 11 non-transmitted (P = 0.2). The VNTR polymorphism in the 5-HTT gene does not appear to be a major risk factor for increasing susceptibility to major psychiatric disorders.",
+ "publisher": "Neurology",
+ "issn": "1526-632X",
+ "date": "2003-10-14",
+ "abstract": "Three patients from a previously described family with autosomal dominant chorea-acanthocytosis were found to have the CTG trinucleotide repeat expansion mutation of the junctophilin-3 gene associated with Huntington's disease-like 2 (HDL2). One of six previously identified patients with HDL2 had acanthocytosis on peripheral blood smear, suggesting that HDL2 should be considered in the differential of chorea-acanthocytosis.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12218657"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:14557581"
},
{
- "id": "pmid:12208565",
+ "id": "pmid:36052448",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/12208565",
- "title": "No association between the serotonergic polymorphisms and incidence of nausea induced by fluvoxamine treatment.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/36052448",
+ "title": "Expanded clinical spectrum of oculopharyngodistal myopathy type 1.",
"type": "article-journal",
- "doi": "10.1016/s0924-977x(02)00056-1",
+ "doi": "10.1002/mus.27717",
"authors": [
- ["Hitoshi", "Takahashi"],
- ["Keizo", "Yoshida"],
- ["Kenich", "Ito"],
- ["Kazuhiro", "Sato"],
- ["Mitsuhiro", "Kamata"],
- ["Hisashi", "Higuchi"],
- ["Tetsuo", "Shimizu"],
- ["Kunihiko", "Ito"],
- ["Kazuyuki", "Inoue"],
- ["Takehiko", "Tezuka"],
- ["Toshio", "Suzuki"],
- ["Tadashi", "Ohkubo"],
- ["Kazunobu", "Sugawara"]
+ ["Takahiro", "Shimizu"],
+ ["Hiroyuki", "Ishiura"],
+ ["Manato", "Hara"],
+ ["Shota", "Shibata"],
+ ["Atsushi", "Unuma"],
+ ["Akatsuki", "Kubota"],
+ ["Kaori", "Sakuishi"],
+ ["Kiyoharu", "Inoue"],
+ ["Jun", "Goto"],
+ ["Yuji", "Takahashi"],
+ ["Yuichiro", "Shirota"],
+ ["Masashi", "Hamada"],
+ ["Jun", "Shimizu"],
+ ["Shoji", "Tsuji"],
+ ["Tatsushi", "Toda"]
],
- "publisher": "European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology",
- "issn": "0924-977X",
- "date": "2002-10-01",
- "abstract": "We investigated the association between serotonergic polymorphisms and incidence of nausea, which is the most frequent side-effect of selective serotonin reuptake inhibiters (SSRIs), in 66 patients treated with fluvoxamine in a protocolized-dosing method. We focused on three polymorphisms of serotonin (5-HT) neuronal systems such as 5-HT transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR), a variable number of tandem repeat (VNTR) polymorphism in the second intron of the 5-HTT gene (STin2) and tryptophan hydroxylase (TPH) gene polymorphism in intron 7 (TPH-A218C), which have been reported to possess positive association with treatment response to SSRIs. In addition to this, the relationship between development of nausea and treatment response was also analyzed. Results suggested that these three polymorphisms did not affect the development of fluvoxamine-induced nausea, and that incidence of nausea was not a phenomenon that predicts the treatment response to fluvoxamine.",
+ "publisher": "Muscle & nerve",
+ "issn": "1097-4598",
+ "date": "2022-09-27",
+ "abstract": "Heterozygous CGG repeat expansions in low-density lipoprotein receptor-related protein 12 (LRP12) have recently been identified as a cause of oculopharyngodistal myopathy (OPDM), and the disease is designated as OPDM type 1 (OPDM1). In contrast to broadening of our knowledge on the genetic background of OPDM, what we know of the clinical phenotype of genetically confirmed OPDM1 remains limited.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12208565"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36052448"
},
{
- "id": "pmid:11979062",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/11979062",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:11979062']' timed out after 3 seconds"
+ "id": "pmid:27072820",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27072820",
+ "title": "MLVA and MLST typing of Brucella from Qinghai, China.",
+ "type": "article-journal",
+ "doi": "10.1186/s40249-016-0123-z",
+ "authors": [
+ ["Jun-Ying", "Ma"],
+ ["Hu", "Wang"],
+ ["Xue-Fei", "Zhang"],
+ ["Li-Qing", "Xu"],
+ ["Gui-Ying", "Hu"],
+ ["Hai", "Jiang"],
+ ["Fang", "Zhao"],
+ ["Hong-Yan", "Zhao"],
+ ["Dong-Ri", "Piao"],
+ ["Yu-Min", "Qin"],
+ ["Bu-Yun", "Cui"],
+ ["Gong-Hua", "Lin"]
+ ],
+ "publisher": "Infectious diseases of poverty",
+ "issn": "2049-9957",
+ "date": "2016-04-13",
+ "abstract": "The Qinghai-Tibet Plateau (QTP) of China is an extensive pastoral and semi-pastoral area, and because of poverty and bad hygiene conditions, Brucella is highly prevalent in this region. In order to adequately prevent this disease in the QTP region it is important to determine the identity of Brucella species that caused the infection.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27072820"
},
{
- "id": "pmid:11978769",
+ "id": "pmid:39848530",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/11978769",
- "title": "Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/39848530",
+ "title": "Phenotypic Heterogeneity of ADTKD-MUC1 Diagnosed Using VNtyper, a Novel Genetic Technique.",
"type": "article-journal",
- "doi": "10.1093/hmg/11.9.1107",
+ "doi": "10.1053/j.ajkd.2024.11.010",
"authors": [
- ["Brinda", "Ravikumar"],
- ["Rainer", "Duden"],
- ["David C", "Rubinsztein"]
+ ["Jessica", "Kachmar"],
+ ["Hassan", "Saei"],
+ ["Vincent", "Morini\u00e8re"],
+ ["Laurence", "Heidet"],
+ ["Bertrand", "Knebelmann"],
+ ["Olivier", "Gribouval"],
+ ["Manon", "Mautret-Godefroy"],
+ ["St\u00e9phane", "Burtey"],
+ ["Vincent", "Vuiblet"],
+ ["Asma", "Alla"],
+ ["Axel", "Ibalanky"],
+ ["Olivier", "Moranne"],
+ ["Mathilde", "Nizon"],
+ ["Benjamin", "Savenkoff"],
+ ["Patrick", "Nitschk\u00e9"],
+ ["Corinne", "Antignac"],
+ ["Guillaume", "Dorval"]
],
- "publisher": "Human molecular genetics",
- "issn": "0964-6906",
- "date": "2002-05-01",
- "abstract": "Protein conformational disorders (PCDs), such as Alzheimer's disease, Huntington's disease (HD), Parkinson's disease and oculopharyngeal muscular dystrophy, are associated with proteins that misfold and aggregate. Here we have used exon 1 of the HD gene with expanded polyglutamine [poly(Q)] repeats and enhanced green fluorescent protein tagged to 19 alanines as models for aggregate-prone proteins, to investigate the pathways mediating their degradation. Autophagy is involved in the degradation of these model proteins, since they accumulated when cells were treated with different inhibitors acting at distinct stages of the autophagy-lysosome pathway, in two different cell lines. Furthermore, rapamycin, which stimulates autophagy, enhanced the clearance of our aggregate-prone proteins. Rapamycin also reduced the appearance of aggregates and the cell death associated with the poly(Q) and polyalanine [poly(A)] expansions. Since rapamycin is used clinically, this drug or related analogues may be suitable candidates for therapeutic investigation in HD and related diseases. We have also re-examined the role of the proteasome, since previous studies in poly(Q) diseases have used lactacystin as an inhibitor--recent studies have shown that lactacystin may also affect lysosomal function. Both lactacystin and the specific proteasomal inhibitor epoxomicin increased soluble protein levels of the poly(Q) constructs, suggesting that these are also cleared by the proteasome. However, while poly(Q) aggregation was enhanced by lactacystin in our inducible PC12 cell model, aggregation was reduced by epoxomicin, suggesting that some other protein(s) induced by epoxomicin may regulate poly(Q) aggregation.",
+ "publisher": "American journal of kidney diseases : the official journal of the National Kidney Foundation",
+ "issn": "1523-6838",
+ "date": "2025-01-22",
+ "abstract": "Molecular diagnosis of autosomal dominant tubulointerstitial kidney disease (ADTKD) due to variants in the MUC1 gene has long been challenging because variants lie in a large variable number of tandem repeat (VNTR) region, making identification impossible using standard short-read techniques. Previously, we addressed this diagnostic limitation by developing a computational pipeline named VNtyper for easier reliable detection of MUC1 VNTR pathogenic variants from short-read sequences. This led to unexpected diagnoses of ADTKD-MUC1 among patients with kidney disease referred for genetic testing, which we report here.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11978769"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39848530"
},
{
- "id": "pmid:11920857",
+ "id": "pmid:39576755",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/11920857",
- "title": "Correlation between serotonin uptake in human blood platelets with the 44-bp polymorphism and the 17-bp variable number of tandem repeat of the serotonin transporter.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/39576755",
+ "title": "Unraveling",
"type": "article-journal",
- "doi": "10.1002/ajmg.10119",
- "authors": [
- ["Rolf", "Kaiser"],
- ["Bruno", "M\u00fcller-Oerlinghausen"],
- ["Diana", "Filler"],
- ["Pierre-Benoit", "Tremblay"],
- ["Anne", "Bergh\u00f6fer"],
- ["Ivar", "Roots"],
- ["J\u00fcrgen", "Brockm\u00f6ller"]
+ "doi": "10.1021/acs.analchem.4c02011",
+ "authors": [
+ ["Amanda", "Helms"],
+ ["Vincent", "Chang"],
+ ["Stacy A", "Malaker"],
+ ["Jennifer S", "Brodbelt"]
],
- "publisher": "American journal of medical genetics",
- "issn": "0148-7299",
- "date": "2002-04-08",
- "abstract": "Dysfunctions of the central serotonin (5-hydroxytryptamine, 5-HT) system seem to be associated with psychiatric disorders such as schizophrenia or depression. Previous studies suggested that a 44-bp insertion/deletion polymorphism of the 5-HT transporter (5-HTT) promoter region might influence the transcriptional activity of the 5-HTT gene, and the insertion variant resulted in increased 5-HTT expression and 5-HT uptake. Moreover, a 17-bp variable number of tandem repeat (VNTR) polymorphism of the second intron may act as a transcriptional regulator with allele dependent differential enhancer-like properties. Since the 5-HTT of human platelets shares many properties with the transporter of neural tissue, platelets are widely used as a surrogate tissue source, possibly reflecting central 5-HT metabolism. Therefore, we investigated the impact of the 44-bp polymorphism and the 17-bp VNTR for 5-HT uptake in platelets of 50 male subjects. We found no significant effect of the 44-bp polymorphism and of the 17-bp VNTR on maximum rate (Vmax) of 5-HT uptake. However, individuals homozygous for the 5-HTT intron 2 allele with 12 repeats (STin2.12) of the 17-bp VNTR appeared to have lower affinity of 5-HT uptake than individuals heterozygous for the STin2.10/STin2.9 allele. This was also observed for the combined analysis of both polymorphisms. In conclusion, we found no association between the different genotypes of the 44-bp polymorphism and the 17-bp VNTR and maximum rate of 5-HT uptake into platelets.",
+ "publisher": "Analytical chemistry",
+ "issn": "1520-6882",
+ "date": "2024-11-22",
+ "abstract": "Deciphering the pattern and abundance of",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11920857"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39576755"
},
{
- "id": "pmid:11741397",
+ "id": "pmid:39325540",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/11741397",
- "title": "Inhibition of polyglutamine aggregation in R6/2 HD brain slices-complex dose-response profiles.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/39325540",
+ "title": "Systematic Screening of Autosomal Dominant Tubulointerstitial Kidney Disease- MUC1 27dupC Pathogenic Variant through Exome Sequencing.",
"type": "article-journal",
- "doi": "10.1006/nbdi.2001.0438",
+ "doi": "10.1681/asn.0000000503",
"authors": [
- ["D L", "Smith"],
- ["R", "Portier"],
- ["B", "Woodman"],
- ["E", "Hockly"],
- ["A", "Mahal"],
- ["W E", "Klunk"],
- ["X J", "Li"],
- ["E", "Wanker"],
- ["K D", "Murray"],
- ["G P", "Bates"]
+ ["Ilias", "Bensouna"],
+ ["Thomas", "Robert"],
+ ["Xavier", "Vanhoye"],
+ ["Marine", "Dancer"],
+ ["Laure", "Raymond"],
+ ["Pierre", "Delaug\u00e8re"],
+ ["Pascale", "Hilbert"],
+ ["Hugues", "Richard"],
+ ["Laurent", "Mesnard"]
],
- "publisher": "Neurobiology of disease",
- "issn": "0969-9961",
- "date": "2001-12-01",
- "abstract": "Huntington's disease (HD) is a late onset neurodegenerative disorder caused by a CAG/polyglutamine (polyQ) repeat expansion. PolyQ aggregates can be detected in the nuclei and processes of neurons in HD patients and mouse models prior to the onset of symptoms. The misfolding and aggregation pathway is an important therapeutic target. To better test the efficacy of aggregation inhibitors, we have developed an organotypic slice culture system. We show here that the formation of polyQ aggregates in hippocampal slices established from the R6/2 mouse follows the same prescribed sequence as occurs in vivo. Using this assay, we show that Congo red and chrysamine G can modulate aggregate formation, but show complex dose-response curves. Oral administration of creatine has been shown to delay the onset of all aspects of the phenotype and neuropathology in R6/2 mice. We show here that creatine can similarly inhibit aggregate formation in the slice culture assay.",
+ "publisher": "Journal of the American Society of Nephrology : JASN",
+ "issn": "1533-3450",
+ "date": "2024-09-26",
+ "abstract": "",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11741397"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39325540"
},
{
- "id": "pmid:11704263",
+ "id": "pmid:37456840",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/11704263",
- "title": "Evaluation of R6/2 HD transgenic mice for therapeutic studies in Huntington's disease: behavioral testing and impact of diabetes mellitus.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/37456840",
+ "title": "VNtyper enables accurate alignment-free genotyping of",
"type": "article-journal",
- "doi": "10.1016/s0166-4328(01)00261-3",
+ "doi": "10.1016/j.isci.2023.107171",
"authors": [
- ["H G", "L\u00fcesse"],
- ["J", "Schiefer"],
- ["A", "Spruenken"],
- ["C", "Puls"],
- ["F", "Block"],
- ["C M", "Kosinski"]
+ ["Hassan", "Saei"],
+ ["Vincent", "Morini\u00e8re"],
+ ["Laurence", "Heidet"],
+ ["Olivier", "Gribouval"],
+ ["Said", "Lebbah"],
+ ["Frederic", "Tores"],
+ ["Manon", "Mautret-Godefroy"],
+ ["Bertrand", "Knebelmann"],
+ ["St\u00e9phane", "Burtey"],
+ ["Vincent", "Vuiblet"],
+ ["Corinne", "Antignac"],
+ ["Patrick", "Nitschk\u00e9"],
+ ["Guillaume", "Dorval"]
],
- "publisher": "Behavioural brain research",
- "issn": "0166-4328",
- "date": "2001-11-29",
- "abstract": "R6/2 transgenic mice express exon 1 of the human Huntington's disease (HD) gene with an increased CAG repeat length. They develop a progressive neurological phenotype, die within 12-14 weeks of age and were also found to develop diabetes mellitus. Since R6/2 mice are broadly used to screen for potential therapies in HD, the aim of this study was (a) to search for behavioral tests that are best applicable to monitor the behavioral abnormalities in therapy studies and (b) to investigate the extent to which diabetes influences the disease phenotype. We found that the rotarod test for motor coordination and the open field test for spontaneous explorative behavior were useful to monitor the progressive behavioral deterioration of R6/2 mice. An accelerating rotarod paradigm was superior over testing with a rotarod at various fixed speeds since it leads to similar results with less repetitive daily trials so that exhaustion cannot contribute substantially to their decline in performance. With the Morris water maze, however, it was only possible to monitor cognitive decline in visuo-spatial learning in the first weeks of disease since, at later stages, mice were not able to learn the task adequately. A latent diabetes mellitus was found in all transgenic mice demonstrated by a pathological glucose tolerance. Only 26% of the mice, however, were found to develop a manifest diabetes with increasing blood glucose levels on normal diet over the disease period. R6/2 mice with manifest and latent diabetes showed no significant differences in survival, weight loss, motor coordination, or spontaneous explorative behavior. These results suggest that diabetes mellitus is not a major contributing factor to the disease phenotype.",
+ "publisher": "iScience",
+ "issn": "2589-0042",
+ "date": "2023-06-17",
+ "abstract": "The human genome comprises approximately 3% of tandem repeats with variable length (VNTR), a few of which have been linked to human rare diseases. Autosomal dominant tubulointerstitial kidney disease-",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11704263"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37456840"
},
{
- "id": "pmid:11689489",
+ "id": "pmid:37316299",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/11689489",
- "title": "Centrosome disorganization in fibroblast cultures derived from R6/2 Huntington's disease (HD) transgenic mice and HD patients.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/37316299",
+ "title": "Hypoxia controls expression of kidney-pathogenic",
"type": "article-journal",
- "doi": "10.1093/hmg/10.21.2425",
+ "doi": "10.26508/lsa.202302078",
"authors": [
- ["K", "Sathasivam"],
- ["B", "Woodman"],
- ["A", "Mahal"],
- ["F", "Bertaux"],
- ["E E", "Wanker"],
- ["D T", "Shima"],
- ["G P", "Bates"]
+ ["Stephanie", "Naas"],
+ ["Ren\u00e9", "Kr\u00fcger"],
+ ["Karl Xaver", "Knaup"],
+ ["Julia", "Naas"],
+ ["Steffen", "Grampp"],
+ ["Mario", "Schiffer"],
+ ["Michael", "Wiesener"],
+ ["Johannes", "Sch\u00f6del"]
],
- "publisher": "Human molecular genetics",
- "issn": "0964-6906",
- "date": "2001-10-01",
- "abstract": "Huntington's disease (HD) is a progressive neurological disorder caused by a CAG/polyglutamine repeat expansion. We have previously generated the R6/2 mouse model that expresses exon 1 of the human HD gene containing CAG repeats in excess of 150. These mice develop a progressive neurological phenotype with a rapid onset and progression. We show here that it is impossible to establish fibroblast lines from these mice at 12 weeks of age, whilst this can be achieved without difficulty at 6 and 9 weeks. Cultures derived from mice at 12 weeks contained a high frequency of dysmorphic cells, including cells with an aberrant nuclear morphology and a high frequency of micronuclei and large vacuoles. All of these features were also present in a line derived from a juvenile HD patient. Fibroblast lines derived from R6/2 mice and from HD patients were found to have a high frequency of multiple centrosomes which could account for all of the observed phenotypes including a reduced mitotic index, high frequency of aneuploidy and persistence of the midbody. We were unable to detect large insoluble polyglutamine aggregates in either the mouse or human lines. We have identified a novel progressive HD pathology that occurs in cells of non-central nervous system origin. An investigation of the pathological consequences of the HD mutation in these cells will provide insight into cellular basis of the disease.",
+ "publisher": "Life science alliance",
+ "issn": "2575-1077",
+ "date": "2023-06-14",
+ "abstract": "The interplay between genetic and environmental factors influences the course of chronic kidney disease (CKD). In this context, genetic alterations in the kidney disease gene",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11689489"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37316299"
},
{
- "id": "pmid:11558794",
+ "id": "pmid:35982790",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/11558794",
- "title": "A disorder similar to Huntington's disease is associated with a novel CAG repeat expansion.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/35982790",
+ "title": "Detecting tandem repeat variants in coding regions using code-adVNTR.",
"type": "article-journal",
- "doi": "",
+ "doi": "10.1016/j.isci.2022.104785",
"authors": [
- ["R L", "Margolis"],
- ["E", "O'Hearn"],
- ["A", "Rosenblatt"],
- ["V", "Willour"],
- ["S E", "Holmes"],
- ["M L", "Franz"],
- ["C", "Callahan"],
- ["H S", "Hwang"],
- ["J C", "Troncoso"],
- ["C A", "Ross"]
+ ["Jonghun", "Park"],
+ ["Mehrdad", "Bakhtiari"],
+ ["Bernt", "Popp"],
+ ["Michael", "Wiesener"],
+ ["Vineet", "Bafna"]
],
- "publisher": "Annals of neurology",
- "issn": "0364-5134",
- "date": "2001-09-01",
- "abstract": "Huntington's disease (HD) is an autosomal dominant disorder characterized by abnormalities of movement, cognition, and emotion and selective atrophy of the striatum and cerebral cortex. While the etiology of HD is known to be a CAG trinucleotide repeat expansion, the pathways by which this mutation causes HD pathology remain unclear. We now report a large pedigree with an autosomal dominant disorder that is clinically similar to HD and that arises from a different CAG expansion mutation. The disorder is characterized by onset in the fourth decade, involuntary movements and abnormalities of voluntary movement, psychiatric symptoms, weight loss, dementia, and a relentless course with death about 20 years after disease onset. Brain magnetic resonance imaging scans and an autopsy revealed marked striatal atrophy and moderate cortical atrophy, with striatal neurodegeneration in a dorsal to ventral gradient and occasional intranuclear inclusions. All tested affected individuals, and no tested unaffecteds, have a CAG trinucleotide repeat expansion of 50 to 60 triplets, as determined by the repeat expansion detection assay. Tests for the HD expansion, for all other known CAG expansion mutations, and for linkage to chromosomes 20p and 4p were negative, indicating that this mutation is novel. Cloning the causative CAG expansion mutation for this new disease, which we have termed Huntington's disease-like 2, may yield valuable insight into the pathogenesis of HD and related disorders.",
+ "publisher": "iScience",
+ "issn": "2589-0042",
+ "date": "2022-07-19",
+ "abstract": "The human genome contains more than one million tandem repeats (TRs), DNA sequences containing multiple approximate copies of a motif repeated contiguously. TRs account for significant genetic variation, with 50\u00a0+ diseases attributed to changes in motif number. A few diseases have been to be caused by small indels in variable number tandem repeats (VNTRs) including poly-cystic kidney disease type 1 (MCKD1) and monogenic type 1 diabetes. However, small indels in VNTRs are largely unexplored mainly due to the long and complex structure of VNTRs with multiple motifs. We developed a method, code-adVNTR, that utilizes multi-motif hidden Markov models to detect both, motif count variation and small\u00a0indels, within VNTRs. In simulated data, code-adVNTR outperformed GATK-HaplotypeCaller\u00a0in calling small indels within large VNTRs. We used code-adVNTR to characterize coding VNTRs in the 1000 genomes data identifying many population-specific variants, and to reliably call",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11558794"
-},
-{
- "id": "pmid:11552131",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/11552131",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:11552131']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35982790"
},
{
- "id": "pmid:11532992",
+ "id": "pmid:33672244",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/11532992",
- "title": "Polyglutamine expansions cause decreased CRE-mediated transcription and early gene expression changes prior to cell death in an inducible cell model of Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/33672244",
+ "title": "Exploring Molecular Contacts of MUC1 at CIN85 Binding Interface to Address Future Drug Design Efforts.",
"type": "article-journal",
- "doi": "10.1093/hmg/10.17.1829",
+ "doi": "10.3390/ijms22042208",
"authors": [
- ["A", "Wyttenbach"],
- ["J", "Swartz"],
- ["H", "Kita"],
- ["T", "Thykjaer"],
- ["J", "Carmichael"],
- ["J", "Bradley"],
- ["R", "Brown"],
- ["M", "Maxwell"],
- ["A", "Schapira"],
- ["T F", "Orntoft"],
- ["K", "Kato"],
- ["D C", "Rubinsztein"]
+ ["Maria Rita", "Gulotta"],
+ ["Serena", "Vittorio"],
+ ["Rosaria", "Gitto"],
+ ["Ugo", "Perricone"],
+ ["Laura", "De Luca"]
],
- "publisher": "Human molecular genetics",
- "issn": "0964-6906",
- "date": "2001-08-15",
- "abstract": "Huntington's disease (HD) is one of 10 known diseases caused by a (CAG)(n) trinucleotide repeat expansion that is translated into an abnormally long polyglutamine tract. We have developed stable inducible neuronal (PC12) cell lines that express huntingtin exon 1 with varying CAG repeat lengths under doxycycline (dox) control. The expression of expanded repeats is associated with aggregate formation, caspase-dependent cell death and decreased neurite outgrowth. Post-mitotic cells expressing mutant alleles were more prone to cell death compared with identical cycling cells. To determine early metabolic changes induced by this mutation in cell models, we studied changes in gene expression after 18 h dox induction, using Affymetrix arrays, cDNA filters and adapter-tagged competitive PCR (ATAC-PCR). At this time point there were low rates of inclusion formation, no evidence of mitochondrial compromise and no excess cell death in the lines expressing expanded compared with wild-type repeats. The expression profiles suggest novel targets for the HD mutation and were compatible with impaired cAMP response element (CRE)-mediated transcription, which we confirmed using CRE-luciferase reporter assays. Reduced CRE-mediated transcription may contribute to the loss of neurite outgrowth and cell death in polyglutamine diseases, as these phenotypes were partially rescued by treating cells with cAMP or forskolin.",
+ "publisher": "International journal of molecular sciences",
+ "issn": "1422-0067",
+ "date": "2021-02-23",
+ "abstract": "The modulation of protein-protein interactions (PPIs) by small molecules represents a valuable strategy for pharmacological intervention in several human diseases. In this context, computer-aided drug discovery techniques offer useful resources to predict the network of interactions governing the recognition process between protein partners, thus furnishing relevant information for the design of novel PPI modulators. In this work, we focused our attention on the MUC1-CIN85 complex as a crucial PPI controlling cancer progression and metastasis. MUC1 is a transmembrane glycoprotein whose extracellular domain contains a variable number of tandem repeats (VNTRs) regions that are highly glycosylated in normal cells and under-glycosylated in cancer. The hypo-glycosylation fosters the exposure of the backbone to new interactions with other proteins, such as CIN85, that alter the intracellular signalling in tumour cells. Herein, different computational approaches were combined to investigate the molecular recognition pattern of MUC1-CIN85 PPI thus unveiling new structural information useful for the design of MUC1-CIN85 PPI inhibitors as potential anti-metastatic agents.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11532992"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33672244"
},
{
- "id": "pmid:11386982",
+ "id": "pmid:33001366",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/11386982",
- "title": "The role of serotonin transporter protein gene in antidepressant-induced mania in bipolar disorder: preliminary findings.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/33001366",
+ "title": "TF-containing MUC1 glycopeptides fail to entice Galectin-1 recognition of tumor-associated Thomsen-Freidenreich (TF) antigen (CD176) in solution.",
"type": "article-journal",
- "doi": "10.1001/archpsyc.58.6.539",
+ "doi": "10.1007/s10719-020-09951-x",
"authors": [
- ["E", "Mundo"],
- ["M", "Walker"],
- ["T", "Cate"],
- ["F", "Macciardi"],
- ["J L", "Kennedy"]
+ ["Forrest G", "FitzGerald"],
+ ["Maria C", "Rodriguez Benavente"],
+ ["Camelia", "Garcia"],
+ ["Yaima", "Rivero"],
+ ["YashoNandini", "Singh"],
+ ["Hongjie", "Wang"],
+ ["Gregg B", "Fields"],
+ ["Mar\u00e9", "Cudic"]
],
- "publisher": "Archives of general psychiatry",
- "issn": "0003-990X",
- "date": "2001-06-01",
- "abstract": "The occurrence of mania during antidepressant treatment is a key issue in the clinical management of bipolar disorder (BP). The serotonin transporter (5-HTT) is the selective site of action of most proserotonergic compounds used to treat bipolar depression. The 5-HTT gene (SLC6A4) has 2 known polymorphisms. The aim of this study was to investigate the role of the SLC6A4 variants in the pathogenesis of antidepressant-induced mania in BP.",
+ "publisher": "Glycoconjugate journal",
+ "issn": "1573-4986",
+ "date": "2020-10-01",
+ "abstract": "Aberrant Mucin-1 (MUC1) glycosylation with the Thomsen-Friedenreich (TF) tumor-associated antigen (CD176) is a hallmark of epithelial carcinoma progression and poor patient prognosis. Recognition of TF by glycan-binding proteins, such as galectins, enables the pathological repercussions of this glycan presentation, yet the underlying binding specificities of different members of the galectin family is a matter of continual investigation. While Galectin-3 (Gal-3) recognition of TF has been well-documented at both the cellular and molecular level, Galectin-1 (Gal-1) recognition of TF has only truly been alluded to in cell-based platforms. Immunohistochemical analyses have purported Gal-1 binding to TF on MUC1 at the cell surface, however binding at the molecular level was inconclusive. We hypothesize that glycan scaffold (MUC1's tandem repeat peptide sequence) and/or multivalency play a role in the binding recognition of TF antigen by Gal-1. In this study we have developed a method for large-scale expression of Gal-1 and its histidine-tagged analog for use in binding studies by isothermal titration calorimetry (ITC) and development of an analytical method based on AlphaScreen technology to screen for Gal-1 inhibitors. Surprisingly, neither glycan scaffold or multivalent presentation of TF antigen on the scaffold was able to entice Gal-1 recognition to the level of affinity expected for functional significance. Future evaluations of the Gal-1/TF binding interaction in order to draw connections between immunohistochemical data and analytical measurements are warranted.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11386982"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33001366"
},
{
- "id": "pmid:11409734",
+ "id": "pmid:30593830",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/11409734",
- "title": "UVB irradiation-induced apoptosis increased in lymphocytes of Huntington's disease patients.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30593830",
+ "title": "Targeting cell-bound MUC1 on myelomonocytic, monocytic leukemias and phenotypically defined leukemic stem cells with anti-SEA module antibodies.",
"type": "article-journal",
- "doi": "10.1097/00001756-200106130-00028",
+ "doi": "10.1016/j.exphem.2018.12.002",
"authors": [
- ["K", "Jakab"],
- ["Z", "Nov\u00e1k"],
- ["J I", "Engelhardt"],
- ["L", "Kem\u00e9ny"],
- ["J", "K\u00e1lm\u00e1n"],
- ["L", "V\u00e9csei"],
- ["I", "Rask\u00f3"]
+ ["Thierry", "Guillaume"],
+ ["Virginie", "Dehame"],
+ ["Patrice", "Chevallier"],
+ ["Pierre", "Peterlin"],
+ ["Alice", "Garnier"],
+ ["Marc", "Gr\u00e9goire"],
+ ["Edward", "Pichinuk"],
+ ["Daniel B", "Rubinstein"],
+ ["Daniel H", "Wreschner"]
],
- "publisher": "Neuroreport",
- "issn": "0959-4965",
- "date": "2001-06-13",
- "abstract": "Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG repeat expansion in the IT-15 gene coding for huntingtin. The mechanism of neuronal degeneration induced by the mutant huntingtin is not known. Apoptosis may play a role in it. Huntingtin is widely expressed in the cells, so abnormalities can be expected also in non-neural tissue. We examined the susceptibility of lymphocytes from HD patients, asymptomatic carriers and normal individuals to UVB irradiation-induced apoptosis. Lymphocytes from eight HD patients and two asymptomatic carriers showed increased apoptotic cell death compared to controls. Our results suggests that sensitivity of HD cells to induced apoptosis is not restricted to neurons.",
+ "publisher": "Experimental hematology",
+ "issn": "1873-2399",
+ "date": "2018-12-26",
+ "abstract": "Cell surface molecules aberrantly expressed or overexpressed by myeloid leukemic cells represent potential disease-specific therapeutic targets for antibodies. MUC1 is a polymorphic glycoprotein, the cleavage of which yields two unequal chains: a large extracellular \u03b1 subunit containing a tandem repeat array bound in a strong noncovalent interaction to a smaller \u03b2 subunit containing the transmembrane and cytoplasmic domains. Because the \u03b1-chain can be released from the cell-bound domains of MUC1, agents directed against the \u03b1-chain will not effectively target MUC1",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11409734"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30593830"
},
{
- "id": "pmid:11406606",
+ "id": "pmid:29520014",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/11406606",
- "title": "Expanded CAG repeats in exon 1 of the Huntington's disease gene stimulate dopamine-mediated striatal neuron autophagy and degeneration.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/29520014",
+ "title": "Single molecule real time sequencing in ADTKD-MUC1 allows complete assembly of the VNTR and exact positioning of causative mutations.",
"type": "article-journal",
- "doi": "10.1093/hmg/10.12.1243",
+ "doi": "10.1038/s41598-018-22428-0",
"authors": [
- ["", "Peters\u00e9n A"],
- ["K E", "Larsen"],
- ["G G", "Behr"],
- ["N", "Romero"],
- ["S", "Przedborski"],
- ["P", "Brundin"],
- ["D", "Sulzer"]
+ ["Andrea", "Wenzel"],
+ ["Janine", "Altmueller"],
+ ["Arif B", "Ekici"],
+ ["Bernt", "Popp"],
+ ["Kurt", "Stueber"],
+ ["Holger", "Thiele"],
+ ["Alois", "Pannes"],
+ ["Simon", "Staubach"],
+ ["Eduardo", "Salido"],
+ ["Peter", "Nuernberg"],
+ ["Richard", "Reinhardt"],
+ ["Andr\u00e9", "Reis"],
+ ["Patrick", "Rump"],
+ ["Franz-Georg", "Hanisch"],
+ ["Matthias T F", "Wolf"],
+ ["Michael", "Wiesener"],
+ ["Bruno", "Huettel"],
+ ["Bodo B", "Beck"]
],
- "publisher": "Human molecular genetics",
- "issn": "0964-6906",
- "date": "2001-06-01",
- "abstract": "Huntington's disease (HD) is caused by an expanded CAG repeat in exon 1 of the gene coding for the huntingtin protein. The cellular pathway by which this mutation induces HD remains unknown, although alterations in protein degradation are involved. To study intrinsic cellular mechanisms linked to the mutation, we examined dissociated postnatally derived cultures of striatal neurons from transgenic mice expressing exon 1 of the human HD gene carrying a CAG repeat expansion. While there was no difference in cell death between wild-type and mutant littermate-derived cultures, the mutant striatal neurons exhibited elevated cell death following a single exposure to a neurotoxic concentration of dopamine. The mutant neurons exposed to dopamine also exhibited lysosome-associated responses including induction of autophagic granules and electron-dense lysosomes. The autophagic/lysosomal compartments co-localized with high levels of oxygen radicals in living neurons, and ubiquitin. The results suggest that the combination of mutant huntingtin and a source of oxyradical stress (provided in this case by dopamine) induces autophagy and may underlie the selective cell death characteristic of HD.",
+ "publisher": "Scientific reports",
+ "issn": "2045-2322",
+ "date": "2018-03-08",
+ "abstract": "Recently, the Mucin-1 (MUC1) gene has been identified as a causal gene of autosomal dominant tubulointerstitial kidney disease (ADTKD). Most causative mutations are buried within a GC-rich 60 basepair variable number of tandem repeat (VNTR), which escapes identification by massive parallel sequencing methods due to the complexity of the VNTR. We established long read single molecule real time sequencing (SMRT) targeted to the MUC1-VNTR as an alternative strategy to the snapshot assay. Our approach allows complete VNTR assembly, thereby enabling the detection of all variants residing within the VNTR and simultaneous determination of VNTR length. We present high resolution data on the VNTR architecture for a cohort of snapshot positive (n\u2009=\u20099) and negative (n\u2009=\u20097) ADTKD families. By SMRT sequencing we could confirm the diagnosis in all previously tested cases, reconstruct both VNTR alleles and determine the exact position of the causative variant in eight of nine families. This study demonstrates that precise positioning of the causative mutation(s) and identification of other coding and noncoding sequence variants in ADTKD-MUC1 is feasible. SMRT sequencing could provide a powerful tool to uncover potential factors encoded within the VNTR that associate with intra- and interfamilial phenotype variability of MUC1 related kidney disease.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11406606"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29520014"
},
{
- "id": "pmid:11279522",
+ "id": "pmid:29328069",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/11279522",
- "title": "Trinucleotide expansion in haploid germ cells by gap repair.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/29328069",
+ "title": "Inhibition of MUC1 biosynthesis via threonyl-tRNA synthetase suppresses pancreatic cancer cell migration.",
"type": "article-journal",
- "doi": "10.1038/86906",
+ "doi": "10.1038/emm.2017.231",
"authors": [
- ["I V", "Kovtun"],
- ["C T", "McMurray"]
+ ["Seung Jae", "Jeong"],
+ ["Jong Hyun", "Kim"],
+ ["Beom Jin", "Lim"],
+ ["Ina", "Yoon"],
+ ["Ji-Ae", "Song"],
+ ["Hee-Sun", "Moon"],
+ ["Doyeun", "Kim"],
+ ["Dong Ki", "Lee"],
+ ["Sunghoon", "Kim"]
],
- "publisher": "Nature genetics",
- "issn": "1061-4036",
- "date": "2001-04-01",
- "abstract": "Huntington disease (HD) is one of eight progressive neurodegenerative disorders in which the underlying mutation is a CAG expansion encoding a polyglutamine tract. The mechanism of trinucleotide expansion is poorly understood. Expansion is mediated by misaligned pairing of repeats and the inappropriate formation of DNA secondary structure as the duplex unpairs. It has never been clear, however, whether duplex unpairing occurs during mitotic replication or during strand-break repair. In simple organisms, trinucleotide expansion arises by replication slippage on either the leading or the lagging strand, homologous recombination, gene conversion, double-strand break repair and base excision repair; it is not clear which of these mechanisms is used in mammalian cells in vivo. We have followed heritable changes in CAG length in male transgenic mice. In germ cells, expansion is limited to the post-meiotic, haploid cell and therefore cannot involve mitotic replication or recombination between a homologous chromosome or a sister chromatid. Our data support a model in which expansion in the germ cells arises by gap repair and depends on a complex containing Msh2. Expansion occurs during gap-filling synthesis when DNA loops comprising the CAG trinucleotide repeats are sealed into the DNA strand.",
+ "publisher": "Experimental & molecular medicine",
+ "issn": "2092-6413",
+ "date": "2018-01-12",
+ "abstract": "Mucin1 (MUC1), a heterodimeric oncoprotein, containing tandem repeat structures with a high proportion of threonine, is aberrantly overexpressed in many human cancers including pancreatic cancer. Since the overall survival rate of pancreatic cancer patients has remained low for several decades, novel therapeutic approaches are highly needed. Intestinal mucin has been known to be affected by dietary threonine supply since de novo synthesis of mucin proteins is sensitive to luminal threonine concentration. However, it is unknown whether biosynthesis of MUC1 is regulated by threonine in human cancers. In this study, data provided suggests that threonine starvation reduces the level of MUC1 and inhibits the migration of MUC1-expressing pancreatic cancer cells. Interestingly, knockdown of threonyl-tRNA synthetase (TRS), an enzyme that catalyzes the ligation of threonine to its cognate tRNA, also suppresses MUC1 levels but not mRNA levels. The inhibitors of TRS decrease the level of MUC1 protein and prohibit the migration of MUC1-expressing pancreatic cancer cells. In addition, a positive correlation between TRS and MUC1 levels is observed in human pancreatic cancer cells. Concurrent with these results, the bioinformatics data indicate that co-expression of both TRS and MUC1 is correlated with the poor survival of pancreatic cancer patients. Taken together, these findings suggest a role for TRS in controlling MUC1-mediated cancer cell migration and provide insight into targeting TRS as a novel therapeutic approach to pancreatic cancer treatment.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11279522"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29328069"
},
{
- "id": "pmid:11260214",
+ "id": "pmid:28581490",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/11260214",
- "title": "The \"flap\" endonuclease gene FEN1 is excluded as a candidate gene implicated in the CAG repeat expansion underlying Huntington disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/28581490",
+ "title": "Assessment of tumor characteristics based on glycoform analysis of membrane-tethered MUC1.",
"type": "article-journal",
- "doi": "10.1034/j.1399-0004.2001.590210.x",
+ "doi": "10.1038/labinvest.2017.53",
"authors": [
- ["C J", "Otto"],
- ["E", "Almqvist"],
- ["M R", "Hayden"],
- ["S E", "Andrew"]
+ ["Atsushi", "Matsuda"],
+ ["Michiyo", "Higashi"],
+ ["Tomomi", "Nakagawa"],
+ ["Seiya", "Yokoyama"],
+ ["Atsushi", "Kuno"],
+ ["Suguru", "Yonezawa"],
+ ["Hisashi", "Narimatsu"]
],
- "publisher": "Clinical genetics",
- "issn": "0009-9163",
- "date": "2001-02-01",
- "abstract": "At least 12 disorders including Huntington disease (HD) are associated with expansion of a trinucleotide repeat (TNR). Factors contributing to the risk of expansion of TNRs and the mechanism of expansion have not been elucidated. Data from Saccharomyces cerevisiae suggest that the flap endonuclease FEN1 plays a role in expansion of repetitive DNA tracts. It has been hypothesized that insufficiency of FEN1 or a mutant FEN1 might contribute to the occurrence of expansion events of long repetitive DNA tracts after polymerase slippage events during lagging strand synthesis. The expression pattern of FEN1 was determined, and ubiquitous tissue expression, including germ cells, suggested that FEN1 has the potential to be involved in HD. Fifteen HD parent/child pairs that demonstrated intergenerational increases in CAG length of greater than 10 repeats were examined for possible mutations or polymorphisms within the FEN1 gene that could underlie the saltatory repeat expansions seen in these individuals. No alterations were observed compared to 50 controls, excluding FEN1 as a trans-acting factor underlying TNR expansion. The identification of a candidate gene(s) in HD or other CAG-expansion disorders implicated in TNR instability will elucidate the mechanism of expansion for this growing family of neurological disorders.",
+ "publisher": "Laboratory investigation; a journal of technical methods and pathology",
+ "issn": "1530-0307",
+ "date": "2017-06-05",
+ "abstract": "Clinical tissue specimens are useful for pathological diagnosis, which is, in some cases, supported by visualization of biomolecule localization. In general, diagnostic specificity in molecular pathology is increased by the acquisition of a probe to distinguish the modification of isomers. Although glycosylation is one of the candidate modifications in a protein, comparative glycan analysis of disease-associated proteins derived from a single tissue section is still challenging because of the lack of analytical sensitivity. Here we demonstrate a possible method for differential glycoform analysis of an endogenous tumor-associated glycoprotein MUC1 by an antibody-overlay lectin microarray. Tissue sections (5\u2009\u03bcm thick) of patients with cholangiocarcinoma (CCA; n=21) and pancreatic ductal adenocarcinoma (PDAC; n=50) were stained with an anti-MUC1 antibody MY.1E12 that was established as a monoclonal antibody recognizing an MUC1 glycosylation isoform with a sialyl-core 1 structure (NeuAc\u03b12-3galactosyl \u03b21-3-N-acetylgalactosamine). MY.1E12-positive tissue areas (2.5\u2009mm",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11260214"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28581490"
},
{
- "id": "pmid:22034471",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/22034471",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:22034471']' timed out after 3 seconds"
+ "id": "pmid:27957769",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27957769",
+ "title": "Microarray Analysis of Antibodies Induced with Synthetic Antitumor Vaccines: Specificity against Diverse Mucin Core Structures.",
+ "type": "article-journal",
+ "doi": "10.1002/chem.201603921",
+ "authors": [
+ ["Christian", "Pett"],
+ ["Hui", "Cai"],
+ ["Jia", "Liu"],
+ ["Bj\u00f6rn", "Palitzsch"],
+ ["Manuel", "Schorlemer"],
+ ["Sebastian", "Hartmann"],
+ ["Natascha", "Stergiou"],
+ ["Mengji", "Lu"],
+ ["Horst", "Kunz"],
+ ["Edgar", "Schmitt"],
+ ["Ulrika", "Westerlind"]
+ ],
+ "publisher": "Chemistry (Weinheim an der Bergstrasse, Germany)",
+ "issn": "1521-3765",
+ "date": "2017-01-23",
+ "abstract": "Glycoprotein research is pivotal for vaccine development and biomarker discovery. Many successful methodologies for reliably increasing the antigenicity toward tumor-associated glycopeptide structures have been reported. Deeper insights into the quality and specificity of the raised polyclonal, humoral reactions are often not addressed, despite the fact that an immunological memory, which produces antibodies with cross-reactivity to epitopes exposed on healthy cells, may cause autoimmune diseases. In the current work, three MUC1 antitumor vaccine candidates conjugated with different immune stimulants are evaluated immunologically. For assessment of the influence of the immune stimulant on antibody recognition, a comprehensive library of mucin 1 glycopeptides (>100 entries) is synthesized and employed in antibody microarray profiling; these range from small tumor-associated glycans (T",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27957769"
},
{
- "id": "pmid:11106399",
+ "id": "pmid:27157321",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/11106399",
- "title": "Transplanted fetal striatum in Huntington's disease: phenotypic development and lack of pathology.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27157321",
+ "title": "Development and Validation of a Mass Spectrometry-Based Assay for the Molecular Diagnosis of Mucin-1 Kidney Disease.",
"type": "article-journal",
- "doi": "10.1073/pnas.97.25.13877",
+ "doi": "10.1016/j.jmoldx.2016.03.003",
"authors": [
- ["T B", "Freeman"],
- ["F", "Cicchetti"],
- ["R A", "Hauser"],
- ["T W", "Deacon"],
- ["X J", "Li"],
- ["S M", "Hersch"],
- ["G M", "Nauert"],
- ["P R", "Sanberg"],
- ["J H", "Kordower"],
- ["S", "Saporta"],
- ["O", "Isacson"]
+ ["Brendan", "Blumenstiel"],
+ ["Matthew", "DeFelice"],
+ ["Ozge", "Birsoy"],
+ ["Anthony J", "Bleyer"],
+ ["Stanislav", "Kmoch"],
+ ["Todd A", "Carter"],
+ ["Andreas", "Gnirke"],
+ ["Kendrah", "Kidd"],
+ ["Heidi L", "Rehm"],
+ ["Lucienne", "Ronco"],
+ ["Eric S", "Lander"],
+ ["Stacey", "Gabriel"],
+ ["Niall J", "Lennon"]
],
- "publisher": "Proceedings of the National Academy of Sciences of the United States of America",
- "issn": "0027-8424",
- "date": "2000-12-05",
- "abstract": "Neural and stem cell transplantation is emerging as a potential treatment for neurodegenerative diseases. Transplantation of specific committed neuroblasts (fetal neurons) to the adult brain provides such scientific exploration of these new potential therapies. Huntington's disease (HD) is a fatal, incurable autosomal dominant (CAG repeat expansion of huntingtin protein) neurodegenerative disorder with primary neuronal pathology within the caudate-putamen (striatum). In a clinical trial of human fetal striatal tissue transplantation, one patient died 18 months after transplantation from cardiovascular disease, and postmortem histological analysis demonstrated surviving transplanted cells with typical morphology of the developing striatum. Selective markers of both striatal projection and interneurons such as dopamine and c-AMP-related phosphoprotein, calretinin, acetylcholinesterase, choline acetyltransferase, tyrosine hydroxylase, calbindin, enkephalin, and substance P showed positive transplant regions clearly innervated by host tyrosine hydroxylase fibers. There was no histological evidence of immune rejection including microglia and macrophages. Notably, neuronal protein aggregates of mutated huntingtin, which is typical HD neuropathology, were not found within the transplanted fetal tissue. Thus, although there is a genetically predetermined process causing neuronal death within the HD striatum, implanted fetal neural cells lacking the mutant HD gene may be able to replace damaged host neurons and reconstitute damaged neuronal connections. This study demonstrates that grafts derived from human fetal striatal tissue can survive, develop, and are unaffected by the disease process, at least for 18 months, after transplantation into a patient with HD.",
+ "publisher": "The Journal of molecular diagnostics : JMD",
+ "issn": "1943-7811",
+ "date": "2016-05-05",
+ "abstract": "Mucin-1 kidney disease, previously described as medullary cystic kidney disease type 1 (MCKD1, OMIM 174000), is an autosomal dominant tubulointerstitial kidney disease recently shown to be caused by a single-base insertion within the variable number tandem repeat region of the MUC1 gene. Because of variable age of disease onset and often subtle signs and symptoms, clinical diagnosis of mucin-1 kidney disease and differentiation from other forms of hereditary kidney disease have been difficult. The causal insertion resides in a variable number tandem repeat region with high GC content, which has made detection by standard next-generation sequencing impossible to date. The inherently difficult nature of this mutation required an alternative method for routine detection and clinical diagnosis of the disease. We therefore developed and validated a mass spectrometry-based probe extension assay with a series of internal controls to detect the insertion event using 24 previously characterized positive samples from patients with mucin-1 kidney disease and 24 control samples known to be wild type for the variant. Validation results indicate an accurate and reliable test for clinically establishing the molecular diagnosis of mucin-1 kidney disease with 100% sensitivity and specificity across 275 tests called.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11106399"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27157321"
},
{
- "id": "pmid:11105061",
+ "id": "pmid:26943180",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/11105061",
- "title": "Huntington disease: DNA analysis in Brazilian population.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26943180",
+ "title": "Testing for the cytosine insertion in the VNTR of the MUC1 gene in a cohort of Italian patients with autosomal dominant tubulointerstitial kidney disease.",
"type": "article-journal",
- "doi": "10.1590/s0004-282x2000000600001",
+ "doi": "10.1007/s40620-016-0282-9",
"authors": [
- ["S", "Raskin"],
- ["N", "Allan"],
- ["H A", "Teive"],
- ["F", "Cardoso"],
- ["M S", "Haddad"],
- ["G", "Levi"],
- ["R", "Boy"],
- ["J", "Lerena Junior"],
- ["V S", "Sotomaior"],
- ["M", "Janzen-D\u00fcck"],
- ["L B", "Jardim"],
- ["F R", "Fellander"],
- ["L A", "Andrade"]
+ ["Claudio", "Musetti"],
+ ["Deepak", "Babu"],
+ ["Ileana", "Fusco"],
+ ["Simona", "Mellone"],
+ ["Andrea", "Zonta"],
+ ["Marco", "Quaglia"],
+ ["Vincenzo", "Cantaluppi"],
+ ["Piero", "Stratta"],
+ ["Mara", "Giordano"]
],
- "publisher": "Arquivos de neuro-psiquiatria",
- "issn": "0004-282X",
- "date": "2000-12-01",
- "abstract": "Huntington disease (HD) is associated with expansions of a CAG trinucleotide repeat in the HD gene. Accurate measurement of a specific CAG repeat sequence in the HD gene in 92 Brazilian controls without HD, 44 Brazilian subjects with clinical findings suggestive of HD and 40 individuals from 6 putative HD families, showed a range from 7 to 33 repeats in normal subjects and 39 to 88 repeats in affected subjects. A trend between early age at onset of first symptoms and increasing number of repeats was seen. Major increase of repeat size through paternal inheritance than through maternal inheritance was observed. Data generated from this study may have significant implications for the etiology, knowledge of the incidence, diagnosis, prognosis, genetic counseling and treatment of HD Brazilian patients.",
+ "publisher": "Journal of nephrology",
+ "issn": "1724-6059",
+ "date": "2016-03-04",
+ "abstract": "Medullary cystic kidney disease type 1 (MCKD1; OMIM #174000) is a familial progressive tubule-interstitial nephropathy belonging to the recently defined group of autosomal dominant tubulointerstitial kidney diseases (ADTKD).",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11105061"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26943180"
},
{
- "id": "pmid:11063736",
+ "id": "pmid:26838233",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/11063736",
- "title": "Gender of the embryo contributes to CAG instability in transgenic mice containing a Huntington's disease gene.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26838233",
+ "title": "Usefulness of Salivary and Serum Auto-antibodies Against Tumor Biomarkers HER2 and MUC1 in Breast Cancer Screening.",
"type": "article-journal",
- "doi": "10.1093/hmg/9.18.2767",
+ "doi": "10.7314/apjcp.2016.17.1.335",
"authors": [
- ["I V", "Kovtun"],
- ["T M", "Therneau"],
- ["C T", "McMurray"]
+ ["Fatna", "Laidi"],
+ ["Amal", "Bouziane"],
+ ["Abdelhamid", "Errachid"],
+ ["Fatima", "Zaoui"]
],
- "publisher": "Human molecular genetics",
- "issn": "0964-6906",
- "date": "2000-11-01",
- "abstract": "Gender is known to influence the transmission of trinucleotide repeats in human disease. However, the molecular basis for the parent-of-origin effect associated with trinucleotide repeat expansion is not known. We have followed, during transmission, the fate of the CAG trinucleotide repeat in a transgene containing the exon 1 portion of the human Huntington's disease (HD) gene. Similar to humans, the mouse transmits expansions predominantly through the male germ line. Surprisingly, we find that the CAG repeat size of the mutant human HD gene is different in male and female progeny from identical fathers. Males predominantly expand the repeat whereas females predominantly contract the repeat. In contrast to the classic definition of imprinting, CAG expansion is influenced by the gender of the embryo. Our results raise the possibility that there are X- or Y-encoded factors that influence repair or replication of DNA in the embryo. Gender dependence in the embryo may explain why expansion in HD from premutation to disease primarily occurs through the paternal line.",
+ "publisher": "Asian Pacific journal of cancer prevention : APJCP",
+ "issn": "2476-762X",
+ "date": "2016-01-01",
+ "abstract": "The aim of this work was to investigate if serum and salivary auto-antibodies, isotypes IgG and IgM, against HER2 and MUC1 tandem repeat fragments could play a role in breast cancer screening.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11063736"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26838233"
},
{
- "id": "pmid:11013077",
+ "id": "pmid:25753030",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/11013077",
- "title": "Identification and characterization of the miniature pig Huntington's disease gene homolog: evidence for conservation and polymorphism in the CAG triplet repeat.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25753030",
+ "title": "In healthy volunteers, immunohistochemistry supports squamous to columnar metaplasia as mechanism of expansion of cardia, aggravated by central obesity.",
"type": "article-journal",
- "doi": "10.1006/geno.2000.6317",
+ "doi": "10.1136/gutjnl-2014-308914",
"authors": [
- ["N", "Matsuyama"],
- ["S", "Hadano"],
- ["K", "Onoe"],
- ["H", "Osuga"],
- ["J", "Showguchi-Miyata"],
- ["Y", "Gondo"],
- ["J E", "Ikeda"]
+ ["Mohammad H", "Derakhshan"],
+ ["Elaine V", "Robertson"],
+ ["Yeong", "Yeh Lee"],
+ ["Tim", "Harvey"],
+ ["Rod K", "Ferrier"],
+ ["Angela A", "Wirz"],
+ ["Clare", "Orange"],
+ ["Stuart A", "Ballantyne"],
+ ["Scott L", "Hanvey"],
+ ["James J", "Going"],
+ ["Kenneth E L", "McColl"]
],
- "publisher": "Genomics",
- "issn": "0888-7543",
- "date": "2000-10-01",
- "abstract": "Huntington's disease (HD) is associated with a significant expansion of a CAG trinucleotide repeat, which results in a lengthened polyglutamine tract in the single gene product, huntingtin, on human 4p16.3. We isolated cDNA clones that encompassed the entire coding sequence of the miniature pig HD gene (Sus HD) from two porcine testis cDNA libraries. The cDNA contig revealed a 12,749-nucleotide transcript coding for a 345-kDa protein (3139 amino acid residues), which exhibited 96% peptide sequence homology to human huntingtin. Northern blot analysis revealed that the Sus HD gene was ubiquitously expressed as two large transcripts of approximately 11 and 13 kb in size in all the tested tissues, much like the human HD gene. The CAG trinucleotide repeat was found to be interrupted by CAA triplets and to encode 17 or 18 consecutive glutamine residues. In our laboratory stock of miniature pig, three allotypes in the triplet repeat sequence were found. Thus, the Sus HD gene closely resembles its human counterpart in terms of sequence and expression pattern. In particular, human-miniature pig similarities in the normal length of the CAG triplet repeat as well as its repeat-number polymorphism may indicate that miniature pig would provide a good animal model for Huntington's disease.",
+ "publisher": "Gut",
+ "issn": "1468-3288",
+ "date": "2015-03-09",
+ "abstract": "Recently, we showed that the length of cardiac mucosa in healthy volunteers correlated with age and obesity. We have now examined the immunohistological characteristics of this expanded cardia to determine whether it may be due to columnar metaplasia of the distal oesophagus.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11013077"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25753030"
},
{
- "id": "pmid:11009201",
+ "id": "pmid:24718884",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/11009201",
- "title": "Environmental stimulation increases survival in mice transgenic for exon 1 of the Huntington's disease gene.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/24718884",
+ "title": "Specific MUC1 splice variants are correlated with tumor progression in esophageal cancer.",
"type": "article-journal",
- "doi": "10.1002/1531-8257(200009)15:5<925::aid-mds1025>3.0.co;2-z",
+ "doi": "10.1007/s00268-014-2523-1",
"authors": [
- ["R J", "Carter"],
- ["M J", "Hunt"],
- ["A J", "Morton"]
+ ["Kolsoum Rezaie", "Kahkhaie"],
+ ["Omeed", "Moaven"],
+ ["Mohammad Reza", "Abbaszadegan"],
+ ["Mehdi", "Montazer"],
+ ["Mehran", "Gholamin"]
],
- "publisher": "Movement disorders : official journal of the Movement Disorder Society",
- "issn": "0885-3185",
- "date": "2000-09-01",
- "abstract": "Mice transgenic for the first exon of the human Huntington's disease (HD) gene carrying an expanded CAG repeat expansion (R6/2 line) develop a progressive neurologic phenotype with symptoms resembling those seen in HD. The overt symptoms of R6/2 mice worsen with age, resulting in a rapid decline in health and premature death between 13 and 18 weeks of age. In this study, we characterized the onset and progression of the overt phenotype in R6/2 mice and examined factors that affect the phenotype and life expectancy of these mice. In particular, the effects of altering home cage environment, through changing feeding regimes and providing environmental stimulation, were investigated. We show that changes in feeding regimes significantly improved the general well-being and life expectancy of R6/2 mice. Furthermore, we find that various forms of environmental stimulation, including regular behavioral testing, significantly improved the survival of R6/2 mice over and above that resulting from the enhanced feeding regime. The fact that environmental stimulation improves the health and life expectancy in R6/2 mice not only enables the mice to serve as more useful research tools, but also suggests that environmental stimulation may have a beneficial impact on the progression of HD in patients.",
+ "publisher": "World journal of surgery",
+ "issn": "1432-2323",
+ "date": "2014-08-01",
+ "abstract": "Mucin 1 (MUC1) is a complex glycoprotein expressed on the apical surface of normal glandular epithelial cells. It plays a role in a number of biologic processes, and its overexpression is associated with various malignancies. A growing body of literature suggests that MUC1 is a potential diagnostic and therapeutic marker. Increasing numbers of variants are being identified for the MUC1 gene, but their role in carcinogenesis is unclear. Alternative splicing and a specific region on a variable number of tandem repeats are characteristic features of MUC1. However, the underlying mechanisms, overall prevalence, and the function of various MUC1 isoforms are not well characterized.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11009201"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24718884"
},
{
- "id": "pmid:10980573",
+ "id": "pmid:24509297",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/10980573",
- "title": "Analysis of CAG and CCG repeats in Huntingtin gene among HD patients and normal populations of India.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/24509297",
+ "title": "Variable clinical presentation of an MUC1 mutation causing medullary cystic kidney disease type 1.",
"type": "article-journal",
- "doi": "10.1038/sj.ejhg.5200515",
+ "doi": "10.2215/cjn.06380613",
"authors": [
- ["S", "Pramanik"],
- ["P", "Basu"],
- ["P K", "Gangopadhaya"],
- ["K K", "Sinha"],
- ["D K", "Jha"],
- ["S", "Sinha"],
- ["S K", "Das"],
- ["B K", "Maity"],
- ["S C", "Mukherjee"],
- ["S", "Roychoudhuri"],
- ["P P", "Majumder"],
- ["N P", "Bhattacharyya"]
+ ["Anthony J", "Bleyer"],
+ ["Stanislav", "Kmoch"],
+ ["Corinne", "Antignac"],
+ ["Vicki", "Robins"],
+ ["Kendrah", "Kidd"],
+ ["John R", "Kelsoe"],
+ ["Gerald", "Hladik"],
+ ["Philip", "Klemmer"],
+ ["Stephen J", "Knohl"],
+ ["Steven J", "Scheinman"],
+ ["Nam", "Vo"],
+ ["Ann", "Santi"],
+ ["Alese", "Harris"],
+ ["Omar", "Canaday"],
+ ["Nelson", "Weller"],
+ ["Peter J", "Hulick"],
+ ["Kristen", "Vogel"],
+ ["Frederick F", "Rahbari-Oskoui"],
+ ["Jennifer", "Tuazon"],
+ ["Constantinos", "Deltas"],
+ ["Douglas", "Somers"],
+ ["Andre", "Megarbane"],
+ ["Paul L", "Kimmel"],
+ ["C John", "Sperati"],
+ ["Avi", "Orr-Urtreger"],
+ ["Shay", "Ben-Shachar"],
+ ["David A", "Waugh"],
+ ["Stella", "McGinn"],
+ ["Anthony J", "Bleyer"],
+ ["Katerina", "Hodanov\u00e1"],
+ ["Petr", "Vylet'al"],
+ ["Martina", "\u017divn\u00e1"],
+ ["Thomas C", "Hart"],
+ ["P Suzanne", "Hart"]
],
- "publisher": "European journal of human genetics : EJHG",
- "issn": "1018-4813",
- "date": "2000-09-01",
- "abstract": "We have analysed the distribution of CAG and adjacent polymorphic CCG repeats in the Huntingtin gene in 28 clinically diagnosed unrelated Huntington's disease (HD) patients and in normal individuals belonging to different ethnic groups of India. The range of expanded CAG repeats in HD patients varied from 41 to 56 repeats, whereas in normal individuals this number varied between 11 and 31 repeats. We identified six CCG alleles from a total of 380 normal chromosomes that were pooled across different ethnic populations of India. There were two predominant alleles: (CCG)7 (72.6%) and (CCG)10 (20%). We report here for the first time one four-repeat CCG allele which has not been found in any population so far. We found 30 haplotypes (two loci CAG-CCG) for 380 normal chromosomes. In the present study, no statistically significant preponderance of expanded HD alleles was found on either (CCG)7 or (CCG)10 backgrounds. Our studies suggest that the overall prevalence of HD in Indian populations may not be as high as in Western populations. Further studies are necessary to identify the origin of HD mutation in these populations.",
+ "publisher": "Clinical journal of the American Society of Nephrology : CJASN",
+ "issn": "1555-905X",
+ "date": "2014-02-07",
+ "abstract": "The genetic cause of medullary cystic kidney disease type 1 was recently identified as a cytosine insertion in the variable number of tandem repeat region of MUC1 encoding mucoprotein-1 (MUC1), a protein that is present in skin, breast, and lung tissue, the gastrointestinal tract, and the distal tubules of the kidney. The purpose of this investigation was to analyze the clinical characteristics of families and individuals with this mutation.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10980573"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24509297"
},
{
- "id": "pmid:10814708",
+ "id": "pmid:23770070",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/10814708",
- "title": "Decreased expression of striatal signaling genes in a mouse model of Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23770070",
+ "title": "Identification of mucins by using a method involving a combination of on-membrane chemical deglycosylation and immunostaining.",
"type": "article-journal",
- "doi": "10.1093/hmg/9.9.1259",
+ "doi": "10.1016/j.jim.2013.06.002",
"authors": [
- ["R", "Luthi-Carter"],
- ["A", "Strand"],
- ["N L", "Peters"],
- ["S M", "Solano"],
- ["Z R", "Hollingsworth"],
- ["A S", "Menon"],
- ["A S", "Frey"],
- ["B S", "Spektor"],
- ["E B", "Penney"],
- ["G", "Schilling"],
- ["C A", "Ross"],
- ["D R", "Borchelt"],
- ["S J", "Tapscott"],
- ["A B", "Young"],
- ["J H", "Cha"],
- ["J M", "Olson"]
+ ["Yu-ki", "Matsuno"],
+ ["Weijie", "Dong"],
+ ["Seiya", "Yokoyama"],
+ ["Suguru", "Yonezawa"],
+ ["Hisashi", "Narimatsu"],
+ ["Akihiko", "Kameyama"]
],
- "publisher": "Human molecular genetics",
- "issn": "0964-6906",
- "date": "2000-05-22",
- "abstract": "To understand gene expression changes mediated by a polyglutamine repeat expansion in the human huntingtin protein, we used oligonucleotide DNA arrays to profile approximately 6000 striatal mRNAs in the R6/2 mouse, a transgenic Huntington's disease (HD) model. We found diminished levels of mRNAs encoding components of the neurotransmitter, calcium and retinoid signaling pathways at both early and late symptomatic time points (6 and 12 weeks of age). We observed similar changes in gene expression in another HD mouse model (N171-82Q). These results demonstrate that mutant huntingtin directly or indirectly reduces the expression of a distinct set of genes involved in signaling pathways known to be critical to striatal neuron function.",
+ "publisher": "Journal of immunological methods",
+ "issn": "1872-7905",
+ "date": "2013-06-14",
+ "abstract": "The characterization of mucins is critically important for gaining insights into the molecular pathology of diseases, including cancers, as well as for the discovery of biomarkers for disease diagnosis. However, no practical method has yet been reported for identifying mucin proteins. Here, we report a technique for immunological identification of mucins separated by supported molecular matrix electrophoresis (SMME), a recently developed membrane electrophoresis method. The technique involves on-membrane deglycosylation of mucins by using mild periodate oxidation/base-catalyzed elimination, followed by immunostaining with an antibody that specifically recognizes the mucin tandem repeat (TR) peptide. We demonstrated the method's feasibility by using MUC1 derived from 2 cancer cell lines, T47D and HPAF-II. The present method shows potential as an alternative approach for the identification of mucins separated by SMME or blotted from conventional gel electrophoresis, on a PVDF membrane.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10814708"
-},
-{
- "id": "pmid:10794362",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/10794362",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:10794362']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23770070"
},
{
- "id": "pmid:10780268",
+ "id": "pmid:23652307",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/10780268",
- "title": "Tentative association of the serotonin transporter with schizophrenia and unipolar depression but not with bipolar disorder in Han Chinese.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23652307",
+ "title": "Autoantibodies to MUC1 glycopeptides cannot be used as a screening assay for early detection of breast, ovarian, lung or pancreatic cancer.",
"type": "article-journal",
- "doi": "",
+ "doi": "10.1038/bjc.2013.214",
"authors": [
- ["W", "Liu"],
- ["N", "Gu"],
- ["G", "Feng"],
- ["S", "Li"],
- ["S", "Bai"],
- ["J", "Zhang"],
- ["T", "Shen"],
- ["H", "Xue"],
- ["G", "Breen"],
- ["D", "St Clair"],
- ["L", "He"]
+ ["B", "Burford"],
+ ["A", "Gentry-Maharaj"],
+ ["R", "Graham"],
+ ["D", "Allen"],
+ ["J W", "Pedersen"],
+ ["A S", "Nudelman"],
+ ["O", "Blixt"],
+ ["E O", "Fourkala"],
+ ["D", "Bueti"],
+ ["A", "Dawnay"],
+ ["J", "Ford"],
+ ["R", "Desai"],
+ ["L", "David"],
+ ["P", "Trinder"],
+ ["B", "Acres"],
+ ["T", "Schwientek"],
+ ["A", "Gammerman"],
+ ["C A", "Reis"],
+ ["L", "Silva"],
+ ["H", "Os\u00f3rio"],
+ ["R", "Hallett"],
+ ["H H", "Wandall"],
+ ["U", "Mandel"],
+ ["M A", "Hollingsworth"],
+ ["I", "Jacobs"],
+ ["I", "Fentiman"],
+ ["H", "Clausen"],
+ ["J", "Taylor-Papadimitriou"],
+ ["U", "Menon"],
+ ["J M", "Burchell"]
],
- "publisher": "Pharmacogenetics",
- "issn": "0960-314X",
- "date": "1999-08-01",
- "abstract": "The serotonin transporter gene (SERT) plays an important role in the serotonin uptake into neurons. Recently, several polymorphisms including a variable-number-tandem-repeat (VNTR) in the second intron and an insertion/deletion polymorphism (5-HTT linked polymorphic region, 5-HTTLPR) were identified and reported to be associated with a variety of mental illnesses, including major depression, bipolar disorder, anxiety-related traits, and autism. In our study, we performed an association study between the SERT VNTR polymorphism and schizophrenia (n = 260), bipolar disorder (n = 137), and unipolar depression (n = 33) in the Han Chinese. A large group of ethnically matched control individuals (n = 362) were also genotyped. Allele 12 of the VNTR polymorphism was associated with schizophrenia (P = 0.007) and unipolar depression (P = 0.011). Bipolar disorder was not associated with the VNTR (P = 0.93). Thus, we conclude that the SERT VNTR polymorphism may be a risk factor for both schizophrenia and unipolar depression, but not for bipolar disorder, in the Han Chinese.",
+ "publisher": "British journal of cancer",
+ "issn": "1532-1827",
+ "date": "2013-05-07",
+ "abstract": "Autoantibodies have been detected in sera before diagnosis of cancer leading to interest in their potential as screening/early detection biomarkers. As we have found autoantibodies to MUC1 glycopeptides to be elevated in early-stage breast cancer patients, in this study we analysed these autoantibodies in large population cohorts of sera taken before cancer diagnosis.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10780268"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23652307"
},
{
- "id": "pmid:10666223",
+ "id": "pmid:21998660",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/10666223",
- "title": "Hodgkin and reed-sternberg cells represent an expansion of a single clone originating from a germinal center B-cell with functional immunoglobulin gene rearrangements but defective immunoglobulin transcription.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21998660",
+ "title": "Mucin variable number tandem repeat polymorphisms and severity of cystic fibrosis lung disease: significant association with MUC5AC.",
"type": "article-journal",
- "doi": "",
+ "doi": "10.1371/journal.pone.0025452",
"authors": [
- ["T", "Marafioti"],
- ["M", "Hummel"],
- ["H D", "Foss"],
- ["H", "Laumen"],
- ["P", "Korbjuhn"],
- ["I", "Anagnostopoulos"],
- ["H", "Lammert"],
- ["G", "Demel"],
- ["J", "Theil"],
- ["T", "Wirth"],
- ["H", "Stein"]
+ ["Xueliang", "Guo"],
+ ["Rhonda G", "Pace"],
+ ["Jaclyn R", "Stonebraker"],
+ ["Clayton W", "Commander"],
+ ["Anthony T", "Dang"],
+ ["Mitchell L", "Drumm"],
+ ["Ann", "Harris"],
+ ["Fei", "Zou"],
+ ["Dallas M", "Swallow"],
+ ["Fred A", "Wright"],
+ ["Wanda K", "O'Neal"],
+ ["Michael R", "Knowles"]
],
- "publisher": "Blood",
- "issn": "0006-4971",
- "date": "2000-02-15",
- "abstract": "Single cell studies aimed at clarifying the nature and clonality of Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin's disease (HD) have so far produced conflicting results. Using an improved single cell procedure, the HRS cells of 25 patients with nodular sclerosing HD lacking B- and T-cell antigens, with and without Epstein-Barr virus infection, were analyzed for the presence of immunoglobulin (Ig) gene rearrangements. One patient with HD developed follicular lymphoma 2 years later. Both lymphomas originated from a common precursor identified as a germinal center B cell. The data show that all but one of the investigated cases harbored rearranged Ig genes, which were clonal in all instances and carried a high load of somatic mutations. The Ig coding capacity was preserved in 18 of the 24 cases (75%) with rearrangements. However, expression of Ig messenger RNA was not detectable in the HRS cells with the exception of Ig kappa light chain expression in some tumor cells of 1 case. The lack of Ig gene transcription in HRS cells was confirmed by analyzing the HD cell lines L428 and KM-H2 in transient transfection experiments. An Ig promoter/enhancer reporter construct showed virtually no activity in these cells compared to 5 control B-cell lines. We conclude that (1) classical HD is a B-cell lymphoma in most instances, (2) HRS cells are clonal without any exception, (3) they are derived from germinal center B-cells that (4) mostly lack crippling mutations but (5) have consistently lost their Ig gene transcription ability, due to functional defects in the Ig gene regulatory elements. (Blood. 2000;95:1443-1450)",
+ "publisher": "PloS one",
+ "issn": "1932-6203",
+ "date": "2011-10-06",
+ "abstract": "Variability in cystic fibrosis (CF) lung disease is partially due to non-CFTR genetic modifiers. Mucin genes are very polymorphic, and mucins play a key role in the pathogenesis of CF lung disease; therefore, mucin genes are strong candidates as genetic modifiers. DNA from CF patients recruited for extremes of lung phenotype was analyzed by Southern blot or PCR to define variable number tandem repeat (VNTR) length polymorphisms for MUC1, MUC2, MUC5AC, and MUC7. VNTR length polymorphisms were tested for association with lung disease severity and for linkage disequilibrium (LD) with flanking single nucleotide polymorphisms (SNPs). No strong associations were found for MUC1, MUC2, or MUC7. A significant association was found between the overall distribution of MUC5AC VNTR length and CF lung disease severity (p = 0.025; n = 468 patients); plus, there was robust association of the specific 6.4 kb HinfI VNTR fragment with severity of lung disease (p = 6.2\u00d710(-4) after Bonferroni correction). There was strong LD between MUC5AC VNTR length modes and flanking SNPs. The severity-associated 6.4 kb VNTR allele of MUC5AC was confirmed to be genetically distinct from the 6.3 kb allele, as it showed significantly stronger association with nearby SNPs. These data provide detailed respiratory mucin gene VNTR allele distributions in CF patients. Our data also show a novel link between the MUC5AC 6.4 kb VNTR allele and severity of CF lung disease. The LD pattern with surrounding SNPs suggests that the 6.4 kb allele contains, or is linked to, important functional genetic variation.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10666223"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21998660"
},
{
- "id": "pmid:10631644",
+ "id": "pmid:21385452",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/10631644",
- "title": "Correlation between triplet repeat expansion and computed tomography measures of caudate nuclei atrophy in Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21385452",
+ "title": "Autoantibodies to aberrantly glycosylated MUC1 in early stage breast cancer are associated with a better prognosis.",
"type": "article-journal",
- "doi": "10.1007/s004150050518",
+ "doi": "10.1186/bcr2841",
"authors": [
- ["B", "Culjkovic"],
- ["O", "Stojkovic"],
- ["N", "Vojvodic"],
- ["M", "Svetel"],
- ["L", "Rakic"],
- ["S", "Romac"],
- ["V", "Kostic"]
+ ["Ola", "Blixt"],
+ ["Deanna", "Bueti"],
+ ["Brian", "Burford"],
+ ["Diane", "Allen"],
+ ["Sylvain", "Julien"],
+ ["Michael", "Hollingsworth"],
+ ["Alex", "Gammerman"],
+ ["Ian", "Fentiman"],
+ ["Joyce", "Taylor-Papadimitriou"],
+ ["Joy M", "Burchell"]
],
- "publisher": "Journal of neurology",
- "issn": "0340-5354",
- "date": "1999-11-01",
- "abstract": "Huntington's disease (HD) is an autosomal dominant, progressive disorder characterized by choreic movements, cognitive decline, and psychiatric manifestations. Eleven patients with HD were retrospectively selected from a larger group of 42 patients based on the similar, early onset of the disease (between 21 and 30 years) and the same duration of HD at the moment of computed tomography (CT) examination (5 years). A significant correlation between the number of CAG trinucleotides and the bicaudate index or the frontal horn index, two indices of caudate atrophy, was found in this group of patients. Our results, although in a small number of patients, suggest that the striatal degeneration, assessed by CT measures, is primarily regulated by the size of expanded CAG repeats.",
+ "publisher": "Breast cancer research : BCR",
+ "issn": "1465-542X",
+ "date": "2011-03-08",
+ "abstract": "Detection of serum biomarkers for early diagnosis of breast cancer remains an important goal. Changes in the structure of O-linked glycans occur in all breast cancers resulting in the expression of glycoproteins that are antigenically distinct. Indeed, the serum assay widely used for monitoring disease progression in breast cancer (CA15.3), detects a glycoprotein (MUC1), but elevated levels of the antigen cannot be detected in early stage patients. However, since the immune system acts to amplify the antigenic signal, antibodies can be detected in sera long before the antigen. We have exploited the change in O-glycosylation to measure autoantibody responses to cancer-associated glycoforms of MUC1 in sera from early stage breast cancer patients.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10631644"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21385452"
},
{
- "id": "pmid:10611371",
+ "id": "pmid:20876819",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/10611371",
- "title": "A serotonin transporter gene intron 2 polymorphic region, correlated with affective disorders, has allele-dependent differential enhancer-like properties in the mouse embryo.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/20876819",
+ "title": "Detection of circulating anti-mucin 1 (MUC1) antibodies in breast tumor patients by indirect enzyme-linked immunosorbent assay using a recombinant MUC1 protein containing six tandem repeats and expressed in Escherichia coli.",
"type": "article-journal",
- "doi": "10.1073/pnas.96.26.15251",
+ "doi": "10.1128/cvi.00142-10",
"authors": [
- ["A", "MacKenzie"],
- ["J", "Quinn"]
+ ["Yan", "Tang"],
+ ["Li", "Wang"],
+ ["Peiyin", "Zhang"],
+ ["Hongfei", "Wei"],
+ ["Rui", "Gao"],
+ ["Xinming", "Liu"],
+ ["Yongli", "Yu"],
+ ["Liying", "Wang"]
],
- "publisher": "Proceedings of the National Academy of Sciences of the United States of America",
- "issn": "0027-8424",
- "date": "1999-12-21",
- "abstract": "Polymorphic regions consisting of a variable number of tandem repeats within intron 2 of the gene coding for the serotonin transporter protein 5-HTT have been associated with susceptibility to affective disorders. We have cloned two of these intronic polymorphisms, Stin2.10 and Stin2.12, into an expression vector containing a heterologous minimal promoter and the bacterial LacZ reporter gene. These constructs were then used to produce transgenic mice. In embryonic day 10.5 embryos, both Stin2.10 and Stin2.12 produced consistent beta-galactosidase expression in the embryonic midbrain, hindbrain, and spinal cord floor plate. However, we observed that the levels of beta-galactosidase expression produced by both the Stin2.10 and Stin2.12 within the rostral hindbrain differed significantly at embryonic day 10.5. Our data suggest that these polymorphic variable number of tandem repeats regions act as transcriptional regulators and have allele-dependent differential enhancer-like properties within an area of the hindbrain where the 5-HTT gene is known to be transcribed at this stage of development.",
+ "publisher": "Clinical and vaccine immunology : CVI",
+ "issn": "1556-679X",
+ "date": "2010-09-28",
+ "abstract": "Mucin 1 (MUC1), a tumor-associated antigen, is a transmembrane glycoprotein expressed by normal epithelial cells and overexpressed by carcinomas of epithelial origin. Autoantibodies against MUC1 are often found in circulation, either free or bound to immune complexes, which might contribute to limit tumor outgrowth and dissemination by antibody-dependent cell-mediated cytotoxicity, and were found favorably predictive of survival in early breast cancer patients. There is no commercial enzyme-linked immunosorbent assay (ELISA) kit for detecting the anti-MUC1 antibodies in human serum thus far. To detect circulating anti-MUC1 antibodies, we established an indirect ELISA (I-ELISA) using a recombinant MUC1 protein containing six tandem repeat sequences of MUC1 after the antigenicity and specificity of the protein were confirmed. The I-ELISA had a sensitivity of 91.3% and a specificity of 94.1% when a competitive I-ELISA was used as a reference test. The results showed that more patients with benign breast tumors (P = 0.001) and breast cancer patients before primary treatment (P = 0.010) were found to have anti-MUC1 IgG than healthy women; anti-MUC1 IgG before primary treatment was found more than after primary treatment (P = 0.016) in breast cancer patients. Interestingly, the anti-MUC1 IgG serum level was reversely correlated to that of CA15-3 antigen in advanced-stage patients (r = -0.4294, P = 0.046). Our study has demonstrated the suitability of the established I-ELISA for detecting circulating anti-MUC1 antibodies in human serum. Furthermore, we found that circulating anti-MUC1 antibodies may still bind MUC1 shed into blood in stage IV breast cancer, which can support the use of MUC1-target immune therapy strategies.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10611371"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20876819"
},
{
- "id": "pmid:10522893",
+ "id": "pmid:19811637",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/10522893",
- "title": "Evidence for the GluR6 gene associated with younger onset age of Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19811637",
+ "title": "Phase I dose escalation pharmacokinetic assessment of intravenous humanized anti-MUC1 antibody AS1402 in patients with advanced breast cancer.",
"type": "article-journal",
- "doi": "10.1212/wnl.53.6.1330",
+ "doi": "10.1186/bcr2409",
"authors": [
- ["M E", "MacDonald"],
- ["J P", "Vonsattel"],
- ["J", "Shrinidhi"],
- ["N N", "Couropmitree"],
- ["L A", "Cupples"],
- ["E D", "Bird"],
- ["J F", "Gusella"],
- ["R H", "Myers"]
+ ["Mark D", "Pegram"],
+ ["Virginia F", "Borges"],
+ ["Nuhad", "Ibrahim"],
+ ["Jyotsna", "Fuloria"],
+ ["Charles", "Shapiro"],
+ ["Susan", "Perez"],
+ ["Karen", "Wang"],
+ ["Franziska", "Schaedli Stark"],
+ ["Nigel", "Courtenay Luck"]
],
- "publisher": "Neurology",
- "issn": "0028-3878",
- "date": "1999-10-12",
- "abstract": "Huntington's disease (HD) is attributed to a triplet CAG repeat mutation, and about half of the variation in onset age can be explained by the size of the repeat expansion. Recently, a TAA repeat polymorphism in close linkage to the kainate receptor, GluR6, was reported related to onset age in HD. We examined this polymorphism in 258 unrelated HD-affected persons (172 from a clinic sample and 86 from a postmortem series). This study confirms that the 155 allele is associated with younger onset age of HD and suggests that it is in linkage disequilibrium with a variant of the GluR6 gene or another gene in this region.",
+ "publisher": "Breast cancer research : BCR",
+ "issn": "1465-542X",
+ "date": "2009-01-01",
+ "abstract": "MUC1 is a cell-surface glycoprotein that establishes a molecular barrier at the epithelial surface and engages in morphogenetic signal transduction. Alterations in MUC1 glycosylation accompany the development of cancer and influence cellular growth, differentiation, transformation, adhesion, invasion, and immune surveillance. A 20-amino-acid tandem repeat that forms the core protein of MUC1 is overexpressed and aberrantly glycosylated in the majority of epithelial tumors. AS1402 (formerly R1550) is a humanized IgG1k monoclonal antibody that binds to PDTR sequences within this tandem repeat that are not exposed in normal cells. AS1402 is a potent inducer of antibody-dependent cellular cytotoxicity (ADCC), specifically against MUC1-expressing tumor cells. The objective of this study was to determine the safety, tolerability, and pharmacokinetic (PK) characteristics of AS1402 monotherapy in patients with locally advanced or metastatic MUC1-positive breast cancer that had progressed after anthracyclines- and taxane-based therapy.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10522893"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19811637"
},
{
- "id": "pmid:10502848",
+ "id": "pmid:19534821",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/10502848",
- "title": "Usefulness of molecular testing in Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19534821",
+ "title": "Induction of protective and therapeutic anti-pancreatic cancer immunity using a reconstructed MUC1 DNA vaccine.",
"type": "article-journal",
- "doi": "",
+ "doi": "10.1186/1471-2407-9-191",
"authors": [
- ["V", "Wang"],
- ["T P", "Yeh"],
- ["C M", "Chen"],
- ["S H", "Yan"],
- ["B W", "Soong"]
+ ["Yefei", "Rong"],
+ ["Dayong", "Jin"],
+ ["Wenchuan", "Wu"],
+ ["Wenhui", "Lou"],
+ ["Danshong", "Wang"],
+ ["Tiantao", "Kuang"],
+ ["Xiaoling", "Ni"],
+ ["Xinyu", "Qin"]
],
- "publisher": "Zhonghua yi xue za zhi = Chinese medical journal; Free China ed",
- "issn": "0578-1337",
- "date": "1999-09-01",
- "abstract": "Uncertainty in diagnosing Huntington's disease (HD) may occur in the absence of a family history or typical movement disorders. HD is characterized by a progressive disturbance of typical movement disorders (i.e., chorea, athetosis), psychiatric symptoms (i.e., depression, insomnia, anxiety, suspiciousness), and cognitive deterioration, in the absence of a dominant family history of similar disorders. Often, some of these symptoms are missing, which makes the diagnosis difficult. In recent years molecular testing has become the gold standard for diagnosing HD. Diagnostic accuracy for HD on genetic screening of patients and their families is important. We evaluated a polymerase chain reaction (PCR) technique for the detection of CAG trinucleotide repeats in the Huntington IT15 gene on chromosome 4 for the diagnosis of HD.",
+ "publisher": "BMC cancer",
+ "issn": "1471-2407",
+ "date": "2009-06-18",
+ "abstract": "Pancreatic cancer is a common, highly lethal disease with a rising incidence. MUC1 is a tumor-associated antigen that is over-expressed in pancreatic adenocarcinoma. Active immunotherapy that targets MUC1 could have great treatment value. Here we investigated the preventive and therapeutic effect of a MUC1 DNA vaccine on the pancreatic cancer.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10502848"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19534821"
},
{
- "id": "pmid:10502825",
+ "id": "pmid:18021186",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/10502825",
- "title": "Increased apoptosis of Huntington disease lymphoblasts associated with repeat length-dependent mitochondrial depolarization.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18021186",
+ "title": "Generation of MUC1-stimulated mononuclear cells using optimized conditions.",
"type": "article-journal",
- "doi": "10.1038/13518",
+ "doi": "10.1111/j.1365-3083.2007.02032.x",
"authors": [
- ["A", "Sawa"],
- ["G W", "Wiegand"],
- ["J", "Cooper"],
- ["R L", "Margolis"],
- ["A H", "Sharp"],
- ["J F", "Lawler"],
- ["J T", "Greenamyre"],
- ["S H", "Snyder"],
- ["C A", "Ross"]
+ ["S E", "Wright"],
+ ["R", "Khaznadar"],
+ ["Z", "Wang"],
+ ["I S", "Quinlin"],
+ ["K A", "Rewers-Felkins"],
+ ["C A", "Phillips"],
+ ["S", "Patel"]
],
- "publisher": "Nature medicine",
- "issn": "1078-8956",
- "date": "1999-10-01",
- "abstract": "Huntington disease (HD) is a genetically dominant condition caused by expanded CAG repeats coding for glutamine in the HD gene product huntingtin. Although HD symptoms reflect preferential neuronal death in specific brain regions, huntingtin is expressed in almost all tissues, so abnormalities outside the brain might be expected. Although involvement of nuclei and mitochondria in HD pathophysiology has been suggested, specific intracellular defects that might elicit cell death have been unclear. Mitochondria dysfunction is reported in HD brains; mitochondria are organelles that regulates apoptotic cell death. We now report that lymphoblasts derived from HD patients showed increased stress-induced apoptotic cell death associated with caspase-3 activation. When subjected to stress, HD lymphoblasts also manifested a considerable increase in mitochondrial depolarization correlated with increased glutamine repeats.",
+ "publisher": "Scandinavian journal of immunology",
+ "issn": "1365-3083",
+ "date": "2007-11-15",
+ "abstract": "Mucin is a glycoprotein found on the surface of cell membranes of adenocarcinomas. The purpose of these studies was to generate MUC1 multiple tandem repeat (VNTR)-stimulated mononuclear cells (M1SMC). We first determined the optimal conditions to influence the immune response. In these studies, peripheral blood mononuclear cells (PBMC), from patients with adenocarcinomas, were stimulated by different numbers of M1SMC stimulations, various concentrations of MUC1 peptide, washing of PBMC prior to stimulation and days in culture, to determine the optimal conditions to influence the immune response. The results of this study indicate that the mononuclear cells (MC) stimulated twice 1 week apart with MUC1 VNTR1 produced a greater specific killing of the breast cancer cell line MCF-7 than the 0, 1, 3 or 4 weekly stimulations. The optimal molarity for inducing cytotoxicity and cytokines (granulocyte macrophage colony-stimulating factor, gamma-interferon and interleukin-10) was 45 x 10(-8) M (1 microg/ml); except for tumour necrosis factor (TNF)-alpha which was 22 x 10(-8) M (0.5 microg/ml). The unwashed MC were superior to washing them with Ficoll-Hypaque. The optimal number of days in culture for cytotoxicity and cytokine production was after two stimulations (i.e. after day 7). Optimum conditions for generation of M1SMC identified in these studies were two stimulations with peptide, concentration of 45 x 10(-8) M (1 microg/ml) peptide, unwashed cells, and after two stimulations or after 8 days in culture. M1SMC were generated from multiple patients with breast cancer which lysed adenocarcinoma cells.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10502825"
-},
-{
- "id": "pmid:10441201",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/10441201",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:10441201']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18021186"
},
{
- "id": "pmid:10434306",
+ "id": "pmid:17694298",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/10434306",
- "title": "Analysis of the subcellular localization of huntingtin with a set of rabbit polyclonal antibodies in cultured mammalian cells of neuronal origin: comparison with the distribution of huntingtin in Huntington's disease autopsy brain.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17694298",
+ "title": "DNA aptamers against the MUC1 tumour marker: design of aptamer-antibody sandwich ELISA for the early diagnosis of epithelial tumours.",
"type": "article-journal",
- "doi": "10.1098/rstb.1999.0459",
+ "doi": "10.1007/s00216-007-1470-1",
"authors": [
- ["J C", "Dorsman"],
- ["M A", "Smoor"],
- ["M L", "Maat-Schieman"],
- ["M", "Bout"],
- ["S", "Siesling"],
- ["S G", "van Duinen"],
- ["J J", "Verschuuren"],
- ["J T", "den Dunnen"],
- ["R A", "Roos"],
- ["G J", "van Ommen"]
+ ["C S M", "Ferreira"],
+ ["K", "Papamichael"],
+ ["G", "Guilbault"],
+ ["T", "Schwarzacher"],
+ ["J", "Gariepy"],
+ ["S", "Missailidis"]
],
- "publisher": "Philosophical transactions of the Royal Society of London. Series B, Biological sciences",
- "issn": "0962-8436",
- "date": "1999-06-29",
- "abstract": "Huntington's disease (HD) is a neurodegenerative disorder with a midlife onset. The disease is caused by expansion of a CAG (glutamine) repeat within the coding region of the HD gene. The molecular mechanism by which the mutated protein causes this disease is still unclear. To study the protein we have generated a set of rabbit polyclonal antibodies raised against different segments of the N-terminal, central and C-terminal parts of the protein. The polyclonal antibodies were affinity purified and characterized in ELISA and Western blotting experiments. All antibodies can react with mouse and human proteins. The specificity of these antibodies is underscored by their recognition of huntingtin with different repeat sizes in extracts prepared from patient-derived lymphoblasts. The antibodies were used in immunofluorescence experiments to study the subcellular localization of huntingtin in mouse neuroblastoma NIE-115 cells. The results indicate that most huntingtin is present in the cytoplasm, whereas a minor fraction is present in the nucleus. On differentiation of the NIE-115 cells in vitro, the subcellular distribution of huntingtin does not change significantly. These results suggest that full-length huntingtin with a normal repeat length can be detected in the nucleus of cycling and non-cycling cultured mammalian cells of neuronal origin. However, in HD autopsy brain the huntingtin-containing neuronal intranuclear inclusions can be detected only with antibodies raised against the N-terminus of huntingtin. Thus several forms of huntingtin display the propensity for nuclear localization, possibly with different functional consequences.",
+ "publisher": "Analytical and bioanalytical chemistry",
+ "issn": "1618-2650",
+ "date": "2007-08-11",
+ "abstract": "Aptamers are functional molecules able to bind tightly and selectively to disease markers, offering great potential for applications in disease diagnosis and therapy. MUC1 is a well-known tumour marker present in epithelial malignancies and is used in immunotherapeutic and diagnostic approaches. We report the selection of DNA aptamers that bind with high affinity and selectivity an MUC1 recombinant protein containing five repeats of the variable tandem repeat region. Aptamers were selected using the SELEX methodology from an initial library containing a 25-base-long variable region for their ability to bind to the unglycosylated form of the MUC1 protein. After ten rounds of in vitro selection and amplification, more than 90% of the pool of sequences consisted of target-binding molecules, which were cloned, sequenced and found to share no sequence consensus. The binding properties of these aptamers were quantified using ELISA and surface plasmon resonance. The lead aptamer sequence was subsequently used in the design of an aptamer-antibody hybrid sandwich ELISA for the identification and quantification of MUC1 in buffered solutions. Following optimisation of the operating conditions, the resulting enzyme immunoassay displayed an EC50 value of 25 microg/ml, a detection limit of 1 microg/ml and a linear range between 8 and 100 microg/ml for the MUC1 five tandem repeat analyte. In addition, recovery studies performed in buffer conditions resulted in averaged recoveries between 98.2 and 101.7% for all spiked samples, demonstrating the usability of the aptamer as a receptor in microtitre-based assays. Our results aim towards the formation of new diagnostic assays against this tumour marker for the early diagnosis of primary or metastatic disease in breast, bladder and other epithelial tumours.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10434306"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17694298"
},
{
- "id": "pmid:10434303",
+ "id": "pmid:17581677",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/10434303",
- "title": "Transgenic mice expressing mutated full-length HD cDNA: a paradigm for locomotor changes and selective neuronal loss in Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17581677",
+ "title": "No evidence of association of MUC-1 genetic polymorphism with embryo implantation failure.",
"type": "article-journal",
- "doi": "10.1098/rstb.1999.0456",
+ "doi": "10.1590/s0100-879x2007000600007",
"authors": [
- ["P H", "Reddy"],
- ["V", "Charles"],
- ["M", "Williams"],
- ["G", "Miller"],
- ["W O", "Whetsell"],
- ["D A", "Tagle"]
+ ["D B", "Dentillo"],
+ ["F R P", "Souza"],
+ ["J", "Meola"],
+ ["G S", "Vieira"],
+ ["M E H D", "Yazlle"],
+ ["L R", "Goulart"],
+ ["L", "Martelli"]
],
- "publisher": "Philosophical transactions of the Royal Society of London. Series B, Biological sciences",
- "issn": "0962-8436",
- "date": "1999-06-29",
- "abstract": "Huntington's disease (HD) is a progressive neurodegenerative disorder characterized clinically by motor and psychiatric disturbances and pathologically by neuronal loss and gliosis (reactive astrocytosis) particularly in the striatum and cerebral cortex. We have recently created HD full-length cDNA transgenic mouse models that may serve as a paradigm for HD. A more detailed characterization of these models is presented here. The transgene encoding normal huntingtin consists of 9417 bp of the huntingtin coding sequences including 16 tandem CAGs coding for polyglutamines as part of exon 1. The transgene is driven by a heterologous cytomegalovirus promoter. Five independent transgenic mouse lines were obtained using this construct. An additional six transgenic lines were obtained using full-length HD constructs that have been modified to include either 48 or 89 CAG repeat expansions. Southern blot and densitometric analyses indicated unique integration sites for the transgene in each of the lines with a copy number ranging from two to 22 copies. Widespread expression of the transgene in brain, heart, spleen, kidney, lung, liver and gonads from each line was determined by Western blot analyses. In the brain, transgene expression was found in cerebral cortex, striatum, hippocampus and cerebellum. Expression of the transgene was as much as five times the endogenous mouse huntingtin level. Phenotypically, only mice expressing 48 or 89 CAG repeats manifested progressive behavioural and motor dysfunction. Early behavioural abnormalities were characterized by trunk curling and clasping of both fore- and hindlimbs when the animals were suspended by their tails. Subsequently, these mice exhibited hyperkinetic movements, including heightened exploratory activities, unidirectional rotational behaviour, backflipping and excessive grooming that lasted for several weeks. Eventually, the animals progressed to a hypokinetic phase consisting of slowed movements and lack of response to sensory stimuli. Urine retention or incontinence was also a prominent feature of the hypokinetic phase. At the end stage of the disease process, HD48(B,D) and HD89(A-C) mice became akinetic just prior to death. Neuropathological examination of mice at various stages indicated that it was only during the hypokinetic phase and thereafter when selective neuronal loss was most apparent. Regions of neurodegeneration and loss included the striatum, cerebral cortex, thalamus and hippocampus. TUNEL staining indicated an apoptotic mode of cell death in these brain regions. Comparative neuronal counts after Nissl staining showed as much as 20% loss of small and medium neurons in the striatum in mice at the hypokinetic and akinetic stages. Reactive astrocytosis accompanied the areas of neurodegeneration and loss. Polyglutamine aggregates in the form of neuronal intranuclear inclusions and diffuse nuclear and perinuclear aggregations were found in a small percentage of neurons, including those in brain regions that are typically spared in HD. This observation suggests that polyglutamine aggregates may not be sufficient to cause neuronal loss in HD. In both behavioural and neuropathological analyses, wild-type and transgenic animals with 16 CAG repeats were indistinguishable from each other and do not exhibit the changes observed for mice carrying the 48 and 89 CAG repeat mutations. Thus, animals expressing the CAG repeat expansions appear to represent clinically analogous models for HD pathogenesis, and may also provide insights into the underlying pathophysiological mechanisms of other triplet repeat disorders.",
+ "publisher": "Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica",
+ "issn": "0100-879X",
+ "date": "2007-06-01",
+ "abstract": "Pregnancy loss can be caused by several factors involved in human reproduction. Although up to 50% of cases remain unexplained, it has been postulated that the major cause of failed pregnancy is an error of embryo implantation. Transmembrane mucin-1 (MUC-1) is a glycoprotein expressed on the endometrial cell surface which acts as a barrier to implantation. The gene that codes for this molecule is composed of a polymorphic tandem repeat of 60 nucleotides. Our objective was to determine if MUC-1 genetic polymorphism is associated with implantation failure in patients with a history of recurrent abortion. The study was conducted on 10 women aged 25 to 35 years with no history of successful pregnancy and with a diagnosis of infertility. The control group consisted of 32 patients aged 25 to 35 years who had delivered at least two full-term live children and who had no history of abortions or fetal losses. MUC-1 amplicons were obtained by PCR and observed on agarose and polyacrylamide gel after electrophoresis. Statistical analysis showed no significant difference in the number of MUC-1 variable number of tandem repeats between these groups (P > 0.05). Our results suggest that there is no effect of the polymorphic MUC-1 sequence on the implantation failure. However, the data do not exclude MUC-1 relevance during embryo implantation. The process is related to several associated factors such as the mechanisms of gene expression in the uterus, specific MUC-1 post-translational modifications and appropriate interactions with other molecules during embryo implantation.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10434303"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17581677"
},
{
- "id": "pmid:10398087",
+ "id": "pmid:17050588",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/10398087",
- "title": "Frequent expansion of Epstein-Barr virus (EBV) infected cells in germinal centres of tonsils from an area with a high incidence of EBV-associated lymphoma.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17050588",
+ "title": "Identification of a novel cancer-specific immunodominant glycopeptide epitope in the MUC1 tandem repeat.",
"type": "article-journal",
- "doi": "10.1002/(sici)1096-9896(199902)187:3<326::aid-path242>3.0.co;2-n",
+ "doi": "10.1093/glycob/cwl061",
"authors": [
- ["I", "Araujo"],
- ["H D", "Foss"],
- ["M", "Hummel"],
- ["I", "Anagnostopoulos"],
- ["H S", "Barbosa"],
- ["A", "Bittencourt"],
- ["H", "Stein"]
+ ["Mads A", "Tarp"],
+ ["Anne Louise", "S\u00f8rensen"],
+ ["Ulla", "Mandel"],
+ ["Hans", "Paulsen"],
+ ["Joy", "Burchell"],
+ ["Joyce", "Taylor-Papadimitriou"],
+ ["Henrik", "Clausen"]
],
- "publisher": "The Journal of pathology",
- "issn": "0022-3417",
- "date": "1999-02-01",
- "abstract": "Burkitt's lymphoma (BL) and Hodgkin's disease (HD) occurring in developing regions are frequently associated with Epstein-Barr virus (EBV) infection and have a high incidence in childhood. Recent genotyping studies indicate that the tumour cells of both neoplasms represent B cells that contain somatically mutated immunoglobulin heavy chain genes. This implies that the precursors of these neoplasms have participated in the germinal centre (GC) reaction. We therefore presumed that normal lymphoid tissues from children living in developing regions would harbour an increased number of EBV-infected cells within the GC, when compared with children living in industrialized nations. To test this hypothesis, hyperplastic tonsils from 40 children living in Bahia (Brazil) and 40 from German children were analysed for the presence of EBV-encoded small nuclear RNA (EBER) and EBV-encoded proteins by in situ hybridization and immunohistology, respectively. Although the overall EBV infection rate was similar in both groups (50 per cent of Bahian vs. 45 per cent of German cases), a significantly higher number of EBER-positive lymphoid cells were found in the GCs of 8/20 EBV-positive tonsils from Brazil (9-89 cells/GC; mean: 14.5 cells/GC per case), while only 3/18 tonsils from Germany displayed a few EBER positive cells (1-9 cells/GC; mean: 0.5 cell/GC per case) in this compartment (p < 0.007). In addition, the EBV-infected GC cells in Bahian samples resembled centroblasts, exhibited mitotic activity, and in two cases showed expression of EBV-encoded latent membrane protein (LMP)-1, findings not present in German samples. These data show that latently EBV-infected cells participate more frequently in GC reactions in developing regions than in industrialized countries and may abnormally express the oncogenic protein LMP-1. This could in part explain the higher incidence in this region of EBV association with lymphomas related to GC cells or their progeny, such as BL and HD.",
+ "publisher": "Glycobiology",
+ "issn": "0959-6658",
+ "date": "2006-10-18",
+ "abstract": "The cell membrane mucin MUC1 is over-expressed and aberrantly glycosylated in many cancers, and cancer-associated MUC1 glycoforms represent potential targets for immunodiagnostic and therapeutic measures. We have recently shown that MUC1 with GalNAcalpha1-O-Ser/Thr (Tn) and NeuAcalpha2-6GalNAcalpha1-O-Ser/Thr (STn) O-glycosylation is a cancer-specific glycoform, and that Tn/STn-MUC1 glycopeptide-based vaccines can override tolerance in human MUC1 transgenic mice and induce humoral immunity with high specificity for MUC1 cancer-specific glycoforms (Sorensen AL, Reis CA, Tarp MA, Mandel U, Ramachandran K, Sankaranarayanan V, Schwientek T, Graham R, Taylor-Papadimitriou J, Hollingsworth MA, et al. 2006. Chemoenzymatically synthesized multimeric Tn/STn MUC1 glycopeptides elicit cancer-specific anti-MUC1 antibody responses and override tolerance. Glycobiology. 16:96-107). In order to further characterize the immune response to Tn/STn-MUC1 glycoforms, we generated monoclonal antibodies with specificity similar to the polyclonal antibody response found in transgenic mice. In the present study, we define the immunodominant epitope on Tn/STn-MUC1 glycopeptides to the region including the amino acids GSTA of the MUC1 20-amino acid tandem repeat (HGVTSAPDTRPAPGSTAPPA). Most other MUC1 antibodies are directed to the PDTR region, although patients with antibodies to the GSTA region have been identified. A panel of other MUC1 glycoform-specific monoclonal antibodies was included for comparison. The study demonstrates that the GSTA region of the MUC1 tandem repeat contains a highly immunodominant epitope when presented with immature short O-glycans. The cancer-specific expression of this glycopeptide epitope makes it a prime candidate for immunodiagnostic and therapeutic measures.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10398087"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17050588"
},
{
- "id": "pmid:10334474",
+ "id": "pmid:16631167",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/10334474",
- "title": "Accurate determination of the number of CAG repeats in the Huntington disease gene using a sequence-specific internal DNA standard.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/16631167",
+ "title": "MUC1 splice variants in human ocular surface tissues: possible differences between dry eye patients and normal controls.",
"type": "article-journal",
- "doi": "10.1034/j.1399-0004.1999.550308.x",
+ "doi": "10.1016/j.exer.2006.01.031",
"authors": [
- ["O", "Bruland"],
- ["E W", "Almqvist"],
- ["Y P", "Goldberg"],
- ["H", "Boman"],
- ["M R", "Hayden"],
- ["P M", "Knappskog"]
+ ["Yoannis", "Imbert"],
+ ["Douglas S", "Darling"],
+ ["Marcia M", "Jumblatt"],
+ ["Gary N", "Foulks"],
+ ["Erica G", "Couzin"],
+ ["Pamela S", "Steele"],
+ ["William W", "Young"]
],
- "publisher": "Clinical genetics",
- "issn": "0009-9163",
- "date": "1999-03-01",
- "abstract": "We have developed a sequence-specific internal DNA size standard for the accurate determination of the number of CAG repeats in the Huntington disease (HD) gene by cloning key fragments (between 15 and 64 CAG repeats) of the HD gene. These fragments, pooled to produce a sequence-specific DNA ladder, enabled us to observe the true number of CAG repeats directly, with no need for calculations. Comparison of the calculated numbers of CAG repeats in the HD gene using this sequence-specific DNA standard with a commercially available standard (GENESCAN-500 TAMRA) showed that the latter underestimated the number of CAG repeats by three when analyzed by capillary electrophoresis on the ABI 310 Genetic Analyzer (POP4 polymer). In contrast, the use of the same standard overestimated the number of CAG repeats by one when the samples were analyzed by denaturing polyacrylamide electrophoresis on ABI 377 DNA Sequencer (6% denaturing polyacrylamide gel). This suggests that our sequence-specific standard provides greater accuracy for the determination of the true number of CAG repeats in the HD gene than commercially available standards. The sequence-specific standard can be radioactively labeled and successfully replace conventional DNA size standards when analyzing polymerase chain reaction (PCR)-amplified HD alleles by denaturing polyacrylamide electrophoresis.",
+ "publisher": "Experimental eye research",
+ "issn": "0014-4835",
+ "date": "2006-04-21",
+ "abstract": "Mucins are highly glycosylated proteins that are vital to the maintenance of healthy epithelial surfaces including the ocular surface. Mucins act as lubricants, protectants, and mediators of signal transduction. The majority of the O-glycosylation sites on the transmembrane mucin MUC1 are found in a highly polymorphic core region containing a variable number of tandem repeats (VNTR). MUC1 alleles can be divided into size classes that contain small (30-45) or large (60-90) numbers of repeats. Although at least 12 splice variants of MUC1 have been found in other tissues, no splice variants have been reported in human ocular surface tissues. We have used RT-PCR to identify MUC1 splice variants that were then confirmed by sequencing. We here report the presence in some samples of human cornea, conjunctiva, and lacrimal gland of MUC1/B which features canonical splicing between exons 1 and 2 and MUC1/A, a transcript that retains 27bp from the 3' end of intron 1 and is predicted to add 9 amino acids to the MUC1 sequence upstream of the tandem repeat region. Cornea and conjunctiva both contain the MUC1/SEC splice variant that lacks the transmembrane domain and, therefore, results in a soluble, secreted form of MUC1. Cornea and conjunctiva also contain MUC1/Y and MUC1/Z(X) variants that lack the tandem repeat region. Cornea, conjunctiva, and lacrimal gland also contain a previously undescribed MUC1 variant transcript, termed MUC1/YI, that retains 99bp from the 5' end and 27bp from the 3' end of the first intron, resulting in a frame shift and premature stop codon. This transcript is predicted to produce a novel 27 amino acid peptide after signal peptidase cleavage. Analysis of brush cytology samples revealed that the percentage of dry eye patients expressing the MUC1/A variant in the conjunctival epithelium is lower than in normal control donors. Western blotting confirmed that MUC1/A is associated with alleles containing the large size class of tandem repeats. Therefore, we propose that one factor in susceptibility to dry eye disease may be the lengths of the MUC1 VNTR in conjunctival epithelium based on the rationale that longer VNTR provide better lubrication and greater protection of the ocular surface against inflammation.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10334474"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16631167"
},
{
- "id": "pmid:10333377",
+ "id": "pmid:16302687",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/10333377",
- "title": "Behavioral effects of tryptophan depletion in seasonal affective disorder associated with the serotonin transporter gene?",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/16302687",
+ "title": "The production and characterization of novel heavy-chain antibodies against the tandem repeat region of MUC1 mucin.",
"type": "article-journal",
- "doi": "10.1016/s0165-1781(99)00009-8",
+ "doi": "10.1080/08820130500265356",
"authors": [
- ["E", "Lenzinger"],
- ["A", "Neumeister"],
- ["N", "Praschak-Rieder"],
- ["K", "Fuchs"],
- ["E", "Gerhard"],
- ["M", "Willeit"],
- ["W", "Sieghart"],
- ["S F", "Kasper"],
- ["K", "Hornik"],
- ["H N", "Aschauer"]
+ ["Fatemeh", "Rahbarizadeh"],
+ ["Mohammad J", "Rasaee"],
+ ["Mehdi", "Forouzandeh"],
+ ["Abdolamir", "Allameh"],
+ ["Ramin", "Sarrami"],
+ ["Habib", "Nasiry"],
+ ["Majid", "Sadeghizadeh"]
],
- "publisher": "Psychiatry research",
- "issn": "0165-1781",
- "date": "1999-03-22",
- "abstract": "There is some evidence that the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) may be involved in the pathogenesis of seasonal affective disorder (SAD). Short-term tryptophan (TRP) depletion was carried out in 18 drug-free remitted patients who met DSM-IV criteria for SAD. Behavioral effects were measured with the Hamilton Depression Rating Scale (HDRS) both 24 h before and 24 h after TRP depletion. Some of the patients showed behavioral responses such as lowered mood, feelings of guilt, loss of interest, agitation, loss of energy, fatigue, social withdrawal, increased appetite, and carbohydrate craving. It was the aim of our study to investigate whether the genotypes of the serotonin transporter gene were associated with symptoms of transient depressive relapse after TRP depletion. In addition, we matched the SAD patients with healthy control subjects to see if alleles and genotypes of the serotonin transporter gene were associated with SAD. High molecular weight DNA was isolated from peripheral blood leukocytes using standard methods. For the 5-HTT receptor gene, a 17-bp repetitive element of intron 2 was genotyped (variable number tandem repeat, VNTR). Alterations in HDRS scores after TRP depletion showed no significant association with alleles or genotypes of the 5-HTT gene, although heterozygotes showed a trend toward increased HDRS scores. The serotonin transporter is known to play a critical role in the termination of serotonergic neurotransmission by sodium-dependent uptake of 5-HT into the presynaptic neuron. The present study in a small group of SAD patients was unable to demonstrate that the 5-HTT gene plays a role in the pathogenesis of SAD or in short-term depressive relapse after TRP depletion.",
+ "publisher": "Immunological investigations",
+ "issn": "0882-0139",
+ "date": "2005-01-01",
+ "abstract": "Camelidae are known to produce immunoglobulins (Igs) devoid of light chains and constant heavy-chain domains (CH1). Antigen-specific fragments of these heavy-chain IgGs (VHH) are of great interest in biotechnology applications. This paper describes the first example of successfully raised heavy-chain antibodies in Camelus dromedarius (single-humped camel) and Camelus bactrianus (two-humped camel) against a MUC1 related peptide that is found to be an important epitope expressed in cancerous tissue. Camels were immunized against a synthetic peptide corresponding to the tandem repeat region of MUC1 mucin and cancerous tissue preparation obtained from patients suffering from breast carcinoma. Three IgG subclasses with different binding properties to protein A and G were purified by affinity chromatography. Both conventional and heavy-chain IgG antibodies were produced in response to MUC1-related peptide. The elicited antibodies could react specifically with the tandem repeat region of MUC1 mucin in an enzyme linked immunosorbant assay (ELISA). Anti-peptide antibodies were purified after passing antiserum over two affinity chromatography columns. Using ELISA, immunocytochemistry and Western blotting, the interaction of purified antibodies with different antigens was evaluated. The antibodies were observed to be selectively bound to antigens namely: MUC1 peptide (tandem repeat region), human milk fat globule membrane (HMFG), deglycosylated human milk fat globule membrane (D-HMFG), homogenized cancerous breast tissue and a native MUC1 purified from ascitic fluid. Ka values of specific polyclonal antipeptide antibodies were estimated in C. dromedarius and C. bactrianus, as 7 x 10(10) M(-1) and 1.4 x 10(10) M(-1) respectively.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10333377"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16302687"
},
{
- "id": "pmid:10196365",
+ "id": "pmid:15729696",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/10196365",
- "title": "A Huntington's disease CAG expansion at the murine Hdh locus is unstable and associated with behavioural abnormalities in mice.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15729696",
+ "title": "Responses of human T cells to peptides flanking the tandem repeat and overlapping the signal sequence of MUC1.",
"type": "article-journal",
- "doi": "10.1093/hmg/8.5.763",
+ "doi": "10.1002/ijc.20949",
"authors": [
- ["P F", "Shelbourne"],
- ["N", "Killeen"],
- ["R F", "Hevner"],
- ["H M", "Johnston"],
- ["L", "Tecott"],
- ["M", "Lewandoski"],
- ["M", "Ennis"],
- ["L", "Ramirez"],
- ["Z", "Li"],
- ["C", "Iannicola"],
- ["D R", "Littman"],
- ["R M", "Myers"]
+ ["Isabel", "Correa"],
+ ["Timothy", "Plunkett"],
+ ["Julia", "Coleman"],
+ ["Eleni", "Galani"],
+ ["Elisabeth", "Windmill"],
+ ["Joy M", "Burchell"],
+ ["Joyce", "Taylor-Papdimitriou"]
],
- "publisher": "Human molecular genetics",
- "issn": "0964-6906",
- "date": "1999-05-01",
- "abstract": "Huntington's disease (HD) is a dominant disorder characterized by premature and progressive neurodegeneration. In order to generate an accurate model of the disease, we introduced an HD-like mutation (an extended stretch of 72-80 CAG repeats) into the endogenous mouse Hdh gene. Analysis of the mutation in vivo reveals significant levels of germline instability, with expansions, contractions and sex-of-origin effects in evidence. Mice expressing full-length mutant protein display abnormal social behaviour in the absence of acute neurodegeneration. Given that psychiatric changes, including irritability and aggression, are common findings in HD patients, our data are consistent with the hypothesis that some clinical features of HD may be caused by pathological processes that precede gross neuronal cell death. This implies that effective treatment of HD may require an understanding and amelioration of these dysfunctional processes, rather than simply preventing the premature death of neurons in the brain. These mice should facilitate the investigation of the molecular mechanisms that underpin the pathway from genotype to phenotype in HD.",
+ "publisher": "International journal of cancer",
+ "issn": "0020-7136",
+ "date": "2005-07-10",
+ "abstract": "The epithelial mucin MUC1 is one of the few tumour-associated antigens identified for breast cancer. Several MUC1-derived peptides binding HLA-A*0201 molecules have been identified that correspond to sequences outside the tandem repeat. Immunisation with some of these peptides induces protective antitumour immunity in mice. Another HLA-A*0201-binding peptide has been identified in a human system. We have evaluated the CD8(+) T-cell responses to all these peptides using peripheral blood lymphocytes from breast cancer patients and normal donors. Specific CD8(+) T-cell responses could be generated in vitro against some of these peptides but only after several rounds of in vitro restimulation, and they did not recognise human cells endogenously expressing the antigen. Nevertheless, T cells recognised by HLA-A*0201 tetramers carrying a peptide from the signal sequence (LLLLTVLTV) could be detected in the peripheral blood of some HLA-A*0201(+) breast cancer patients but not in healthy adults. This peptide is the only one of those tested which was identified in the human system, and the results emphasize the potential problems involved in translation of data from laboratory animal models to the human system.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10196365"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15729696"
},
{
- "id": "pmid:10098889",
+ "id": "pmid:15604091",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/10098889",
- "title": "Brain neurotransmitter deficits in mice transgenic for the Huntington's disease mutation.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15604091",
+ "title": "Thomsen-Friedenreich antigen expression in gastric carcinomas is associated with MUC1 mucin VNTR polymorphism.",
"type": "article-journal",
- "doi": "10.1046/j.1471-4159.1999.721773.x",
+ "doi": "10.1093/glycob/cwi027",
"authors": [
- ["G P", "Reynolds"],
- ["C F", "Dalton"],
- ["C L", "Tillery"],
- ["L", "Mangiarini"],
- ["S W", "Davies"],
- ["G P", "Bates"]
+ ["F", "Santos-Silva"],
+ ["A", "Fonseca"],
+ ["T", "Caffrey"],
+ ["F", "Carvalho"],
+ ["P", "Mesquita"],
+ ["C", "Reis"],
+ ["R", "Almeida"],
+ ["L", "David"],
+ ["M A", "Hollingsworth"]
],
- "publisher": "Journal of neurochemistry",
- "issn": "0022-3042",
- "date": "1999-04-01",
- "abstract": "Huntington's disease (HD) is associated with an expansion in the CAG repeat sequence of a gene on chromosome 4, resulting in a neurodegenerative process particularly affecting the striatum and with profound but selective changes in content of various neurotransmitters. Recently, transgenic mice expressing a fragment of the human HD gene containing a large CAG expansion have been generated; these mice exhibit a progressive neurological phenotype that includes motor disturbances, as well as neuronal deficits. To investigate their underlying neurotransmitter pathology, we have determined concentrations of GABA, glutamate, and the monoamine neurotransmitters in several brain regions in these mice and control animals at times before and after the emergence of the behavioural phenotype. In contrast to the findings in HD, striatal GABA was unaffected, although a deficit was observed in the cerebellum, consistent with a dysfunction of Purkinje cells. Losses of the monoamine transmitters were observed, some of which are not seen in HD. Thus, 5-hydroxytryptamine and, to a greater extent, 5-hydroxyindoleacetic acid levels were diminished in all brain regions studied, and noradrenaline was particularly affected in the hippocampus. Dopamine was decreased in the striatum in older animals, parallelling evidence for diminished dopaminergic activity in HD.",
+ "publisher": "Glycobiology",
+ "issn": "0959-6658",
+ "date": "2004-12-15",
+ "abstract": "Aberrant glycosylation of mucins is a common phenomenon associated with oncogenic transformation. We investigated the association between expression of the tumor-associated antigens T, Tn, and sialyl-Tn and polymorphism in the length of the MUC1 mucin tandem repeat in a series of gastric carcinomas. We further evaluated the relevance of MUC1 tandem repeat length on the expression of these tumor-associated carbohydrate antigens (TACAs) using a gastric carcinoma cell line model expressing recombinant MUC1 constructs carrying 0, 3, 9, and 42 repeats. Gastric carcinomas showed a high prevalence of Tn and sialyl-Tn antigens, whereas T antigen was less frequently expressed. The expression of T antigen was significantly higher in gastric carcinomas from patients homozygous for MUC1 large tandem repeat alleles. No significant associations were found for Tn and sialyl-Tn antigens. This novel association was reinforced by the gastric carcinoma cell line model experiments, where de novo expression of T antigen was detected in clones transfected with larger VNTR regions. Our results indicate that polymorphism in the MUC1 tandem repeat influences the expression of TACAs in gastric cancer cells and may therefore allow the identification of subgroups of patients that develop more aggressive tumors expressing T antigen.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10098889"
-},
-{
- "id": "pmid:10091627",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/10091627",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:10091627']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15604091"
},
{
- "id": "pmid:10051007",
+ "id": "pmid:15041735",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/10051007",
- "title": "Age of onset in Huntington disease: sex specific influence of apolipoprotein E genotype and normal CAG repeat length.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15041735",
+ "title": "A human cytotoxic T-lymphocyte epitope and its agonist epitope from the nonvariable number of tandem repeat sequence of MUC-1.",
"type": "article-journal",
- "doi": "",
+ "doi": "10.1158/1078-0432.ccr-1011-03",
"authors": [
- ["P", "Kehoe"],
- ["M", "Krawczak"],
- ["P S", "Harper"],
- ["M J", "Owen"],
- ["A L", "Jones"]
+ ["Kwong-Yok", "Tsang"],
+ ["Claudia", "Palena"],
+ ["James", "Gulley"],
+ ["Philip", "Arlen"],
+ ["Jeffrey", "Schlom"]
],
- "publisher": "Journal of medical genetics",
- "issn": "0022-2593",
- "date": "1999-02-01",
- "abstract": "Age of onset (AO) of Huntington disease (HD) is known to be correlated with the length of an expanded CAG repeat in the HD gene. Apolipoprotein E (APOE) genotype, in turn, is known to influence AO in Alzheimer disease, rendering the APOE gene a likely candidate to affect AO in other neurological diseases too. We therefore determined APOE genotype and normal CAG repeat length in the HD gene for 138 HD patients who were previously analysed with respect to CAG repeat length. Genotyping for APOE was performed blind to clinical information. In addition to highlighting the effect of the normal repeat length upon AO in maternally inherited HD and in male patients, we show that the APOE epsilon2epsilon3 genotype is associated with significantly earlier AO in males than in females. Such a sex difference in AO was not apparent for any of the other APOE genotypes. Our findings suggest that subtle differences in the course of the neurodegeneration in HD may allow interacting genes to exert gender specific effects upon AO.",
+ "publisher": "Clinical cancer research : an official journal of the American Association for Cancer Research",
+ "issn": "1078-0432",
+ "date": "2004-03-15",
+ "abstract": "MUC-1/DF-3 remains an attractive target for vaccine therapy. It is overexpressed in the majority of human carcinomas and multiple myeloma. Clinical trials using MUC-1-based vaccines have demonstrated safety, clinical responses, and the induction of T-cell responses directed against MUC-1. Previous studies in experimental models and in clinical trials have demonstrated that altering the amino acid sequence of a \"self\" epitope can lead to the generation of an enhancer agonist epitope capable of eliciting stronger T-cell responses than the native epitope can.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10051007"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15041735"
},
{
- "id": "pmid:10023115",
+ "id": "pmid:14707484",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/10023115",
- "title": "Analysis of CAG repeat expansion in Huntington's disease gene (IT 15) in a Hungarian population.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/14707484",
+ "title": "In vivo glycosylation of MUC1 in airway epithelial cells.",
"type": "article-journal",
- "doi": "10.1159/000008013",
+ "doi": "10.1023/b:glyc.0000004009.24191.d3",
"authors": [
- ["K", "Jakab"],
- ["G", "G\u00e1rdi\u00e1n"],
- ["E", "Endreffy"],
- ["T", "Kalm\u00e1r"],
- ["C", "Bachrati"],
- ["L", "V\u00e9csei"],
- ["I", "Rask\u00f3"]
+ ["Howard S", "Silverman"],
+ ["Mark", "Sutton-Smith"],
+ ["Paul", "Heal"],
+ ["Simon", "Parry"],
+ ["Timea", "Palmai-Pallag"],
+ ["Shih-Hsing", "Leir"],
+ ["Howard R", "Morris"],
+ ["Anne", "Dell"],
+ ["Ann", "Harris"]
],
- "publisher": "European neurology",
- "issn": "0014-3022",
- "date": "1999-01-01",
- "abstract": "Huntington's disease (HD) is a neurodegenerative disorder with autosomal dominant inheritance. The genetic defect is a CAG trinucleotide repeat expansion at the 5' end of the IT 15 gene on chromosome 4. This gene has not been analyzed in the Hungarian population yet. To obtain data DNA from 26 HD patients, 18 members of their families and 70 normal controls was amplified in the involved region by polymerase chain reaction. The CAG repeat numbers varied from 37 to 70 (median: 43) in HD patients and asymptomatic carriers, while individuals of the normal control group had 10-36 CAG repeat numbers (median: 18). The length of CAG repeat expansion in Hungarian HD patients was similar to that reported from other countries. The group of normal controls had the same CAG repeat expansion as populations reported from Western European countries. It is a useful piece of data for population genetics to prove that the population of Hungary is a m\u00e9lange of different nations that influenced the history of the country in the last 11 centuries. As opposed to this, the only closely related nation, the Finnish, was genetically more isolated during this time, so the frequency of HD (and also the number of CAG repeats in normal individuals) proved to be exceptionally low.",
+ "publisher": "Glycoconjugate journal",
+ "issn": "0282-0080",
+ "date": "2002-07-01",
+ "abstract": "The O-glycans that decorate mucin glycoproteins contribute to the biophysical and biochemical properties of these molecules and hence their function as a barrier and lubricant on epithelial surfaces. Alterations in mucin O-glycosylation in certain diseases may contribute to pathology. It is known that both the host cell type and the amino acid sequence of the mucin tandem repeat contribute to the O-glycosylation of a mucin molecule. We expressed an epitope-tagged MUC1 mucin cDNA construct in the airway cell line 16HBE14o- and the colon carcinoma cell line Caco2 and used Fast Atom Bombardment Mass Spectrometry to evaluate the contribution of the host cell to differences in O-glycosylation of a single mucin. Many of the glycans detected on the MUC1 mucin were common to both cell types, as would be predicted from biosynthetic constraints. However, MUC1 synthesized in the airway cell line showed comparatively low levels of sialylation but carried a range of oligo-N-acetyllactosamine structures that were not seen in the colon carcinoma cell line.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10023115"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:14707484"
},
{
- "id": "pmid:9949443",
+ "id": "pmid:12747745",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/9949443",
- "title": "Preimplantation diagnosis for Huntington's disease (HD): clinical application and analysis of the HD expansion in affected embryos.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/12747745",
+ "title": "MUC1-like tandem repeat proteins are broadly immunogenic in cancer patients.",
"type": "article-journal",
- "doi": "10.1002/(sici)1097-0223(199812)18:13<1427::aid-pd493>3.0.co;2-3",
+ "doi": "",
"authors": [
- ["K", "Sermon"],
- ["V", "Goossens"],
- ["S", "Seneca"],
- ["W", "Lissens"],
- ["A", "De Vos"],
- ["M", "Vandervorst"],
- ["A", "Van Steirteghem"],
- ["I", "Liebaers"]
+ ["Joseph A", "Mollick"],
+ ["F Stephen", "Hodi"],
+ ["Robert J", "Soiffer"],
+ ["Lee M", "Nadler"],
+ ["Glenn", "Dranoff"]
],
- "publisher": "Prenatal diagnosis",
- "issn": "0197-3851",
- "date": "1998-12-01",
- "abstract": "Huntington's disease (HD) is an autosomal dominant disease characterized by motor disturbance, cognitive loss and psychiatric manifestations, starting between the fourth and the fifth decade, followed by death within 10-20 years of onset of the disease. The disease-causing mutation is an expansion of a CAG triplet repeat at the 5' coding end of the Huntington gene. We have developed a single-cell PCR assay for the HD gene in order to propose preimplantation genetic diagnosis (PGD) for the couples at risk. We present here our first results with our first nine PGD cycles and also discuss the behaviour of the disease-causing expansion in pre-implantation embryos.",
+ "publisher": "Cancer immunity",
+ "issn": "1424-9634",
+ "date": "2003-03-17",
+ "abstract": "The identification of antigens mediating tumor rejection is an important goal of cancer immunology. The SEREX technology utilizes antibodies from cancer patients to identify candidate antigens from tumor-derived cDNA expression libraries. Using sera from a long-term surviving metastatic melanoma patient vaccinated with irradiated, autologous tumor cells engineered to secrete granulocyte-macrophage colony stimulating factor (GM-CSF), we identified an antigen reported to be a putative opioid growth factor receptor (OGFr). The human immune response to OGFr exhibits three features shared with other tumor antigens. First, the protein is an intracellular antigen found in both nucleus and cytoplasm. Second, part of the antibody response is directed at a putative protein product encoded by an alternative reading frame (ARF). Third, part of the antibody response is directed at a portion of the molecule that bears a striking resemblance to the extracellular domain of MUC1, both with respect to primary structure and size polymorphism. Antibody responses to OGFr and a synthetic peptide representing a putative alternative reading frame product (OGFr-ARF) were frequently found in cancer patients. 11/45 (24%) melanoma patients had antibodies to OGFr and 5/45 (11%) had antibodies to OGFr-ARF. Moreover, 5/24 (21%) lung cancer, 4/25 (16%) prostate cancer, and 5/6 breast or ovarian cancer patients had antibodies to OGFr, the alternative frame product, or both. These data add to the growing list of tumor antigens that appear to be translated in two frames, and suggest that OGFr and OGFr-ARF may be useful targets for vaccination.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9949443"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12747745"
},
{
- "id": "pmid:9818876",
+ "id": "pmid:12090474",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/9818876",
- "title": "Larger CAG expansions in skeletal muscle compared with lymphocytes in Kennedy disease but not in Huntington disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/12090474",
+ "title": "Non-glycosylated tandem repeats of MUC1 facilitate attachment of breast tumor cells to normal human lung tissue and immobilized extracellular matrix proteins (ECM) in vitro: potential role in metastasis.",
"type": "article-journal",
- "doi": "10.1212/wnl.51.5.1442",
+ "doi": "10.1023/a:1015590515957",
"authors": [
- ["T", "Ansved"],
- ["A", "Lundin"],
- ["M", "Anvret"]
+ ["Pawel", "Ciborowski"],
+ ["Olivera J", "Finn"]
],
- "publisher": "Neurology",
- "issn": "0028-3878",
- "date": "1998-11-01",
- "abstract": "The size of CAG repeats was compared in lymphocytes and skeletal muscle from nine patients with Huntington disease (HD) and two patients with Kennedy disease (KD). In HD, the number of CAG repeats did not differ between lymphocytes and skeletal muscle. In the two KD patients, however, the CAG expansion was larger in muscle than in lymphocytes. The difference in trinucleotide expansion between lymphocytes and muscle cells is not a universal phenomenon in trinucleotide repeat disorders, but seems to occur in disorders primarily affecting the neuromuscular system.",
+ "publisher": "Clinical & experimental metastasis",
+ "issn": "0262-0898",
+ "date": "2002-01-01",
+ "abstract": "MUC1 is a transmembrane glycoprotein abundantly expressed on the apical surface of human ductal epithelial cells and over entire cell surface of tumors originating from those cells. It is 300 to 500 nm long and has a rigid, rod-like structure protruding from the cell surface. MUC1 expressed by normal cells has heavily O-glycosylated tandem repeat domain while MUC1 on malignant cells is aberrantly O-glycosylated. Substantially reduced (aberrant) glycosylation of the tandem repeat region of tumor MUC1 results in uncovering of the polypeptide core. This new structural feature may play an important role in the attachment of metastasizing tumor cells to tissues at distant sites. We show that MDA-MB-231 cells attaching to the immobilized extracellular matrix proteins (ECM) are higher MUC1 expressers than those non-attaching and that the attachment is inhibited by the addition of non-glycosylated, MUC1 peptide. This 100 a.a. peptide composed of 5 tandem repeats from the tandem repeat domain mimics the forms of MUC1 found in ascites fluid of cancer patients. We also show that this synthetic form of MUC1 inhibited attachment of breast tumor cells to sections of normal human lung tissue and immobilized ECM. We did not find correlation between the expression of Tn (GalNAc-Ser/Thr) epitope and the ability of tumor cells to adhere to the immobilized ECM. These results indicate that the non-glycosylated form of MUC1 plays a role in the initial attachment of carcinoma cells to tissues at distant sites, which may facilitate establishment of metastatic foci.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9818876"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12090474"
},
{
- "id": "pmid:9806905",
+ "id": "pmid:11445551",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/9806905",
- "title": "Isolation and characterization of the rat huntingtin promoter.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11445551",
+ "title": "In vivo glycosylation of mucin tandem repeats.",
"type": "article-journal",
- "doi": "10.1042/bj3360227",
+ "doi": "10.1093/glycob/11.6.459",
"authors": [
- ["C", "Holzmann"],
- ["W", "M\u00e4ueler"],
- ["D", "Petersohn"],
- ["T", "Schmidt"],
- ["G", "Thiel"],
- ["J T", "Epplen"],
- ["O", "Riess"]
+ ["H S", "Silverman"],
+ ["S", "Parry"],
+ ["M", "Sutton-Smith"],
+ ["M D", "Burdick"],
+ ["K", "McDermott"],
+ ["C J", "Reid"],
+ ["S K", "Batra"],
+ ["H R", "Morris"],
+ ["M A", "Hollingsworth"],
+ ["A", "Dell"],
+ ["A", "Harris"]
],
- "publisher": "The Biochemical journal",
- "issn": "0264-6021",
- "date": "1998-11-15",
- "abstract": "Huntington's disease (HD) is a neurodegenerative disorder caused by a (CAG)>37 repeat expansion in a novel gene of unknown function. Although the huntingtin gene is expressed in neuronal and non-neuronal tissues, the disease affects nerve cells of selected regional areas of the central nervous system. To gain insight into the regulation of the HD gene we analysed 1348 bp of the rat huntingtin promoter region. This region lacks a TATA and a CAAT box, is rich in GC content and has several consensus sequences for binding sites for SP1, PEA3, Sif and H2A. The stretch between nucleotides -56 and -206 relative to the first ATG is highly conserved between human and rodents and it harbours several potential binding sites for transcription factors. We analysed deletion mutants fused with the chloramphenicol acetyltransferase reporter gene in transfected, HD-expressing neuronal (NS20Y, NG108-15) and non-neuronal Chinese hamster ovary cell lines. Hence these cells should contain the required trans-acting factors necessary for HD gene expression. Partial deletion of the evolutionarily conserved part of the promoter significantly decreases the activity in both neuronal and non-neuronal cells, indicating that the core promoter activity is located between nucleotides -332 and -15. DNase I footprinting and electrophoretic mobility-shift assays were used to define the nucleotide positions and binding affinity of DNA-protein interactions.",
+ "publisher": "Glycobiology",
+ "issn": "0959-6658",
+ "date": "2001-06-01",
+ "abstract": "The biochemical and biophysical properties of mucins are largely determined by extensive O-glycosylation of serine- and threonine-rich tandem repeat (TR) domains. In a number of human diseases aberrant O-glycosylation is associated with variations in the properties of the cell surface-associated and secreted mucins. To evaluate in vivo the O-glycosylation of mucin TR domains, we generated recombinant chimeric mucins with TR sequences from MUC2, MUC4, MUC5AC, or MUC5B, which were substituted for the native TRs of epitope-tagged MUC1 protein (MUC1F). These hybrid mucins were extensively O-glycosylated and showed the expected association with the cell surface and release into culture media. The presence of different TR domains within the chimeric mucins appears to have limited influence on their posttranslational processing. Alterations in glycosylation were detailed by fast atom bombardment mass spectrometry and reactivity with antibodies against particular blood-group and tumor-associated carbohydrate antigens. Future applications of these chimeras will include investigations of mucin posttranslational modification in the context of disease.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9806905"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11445551"
},
{
- "id": "pmid:9792871",
+ "id": "pmid:11169964",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/9792871",
- "title": "A Huntington disease-like neurodegenerative disorder maps to chromosome 20p.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11169964",
+ "title": "Identification of three non-VNTR MUC1-derived HLA-A*0201-restricted T-cell epitopes that induce protective anti-tumor immunity in HLA-A2/K(b)-transgenic mice.",
"type": "article-journal",
- "doi": "10.1086/302093",
+ "doi": "10.1002/1097-0215(200002)9999:9999<::aid-ijc1051>3.0.co;2-z",
"authors": [
- ["F", "Xiang"],
- ["E W", "Almqvist"],
- ["M", "Huq"],
- ["A", "Lundin"],
- ["M R", "Hayden"],
- ["L", "Edstr\u00f6m"],
- ["M", "Anvret"],
- ["Z", "Zhang"]
+ ["L C", "Heukamp"],
+ ["S H", "van der Burg"],
+ ["J W", "Drijfhout"],
+ ["C J", "Melief"],
+ ["J", "Taylor-Papadimitriou"],
+ ["R", "Offringa"]
],
- "publisher": "American journal of human genetics",
- "issn": "0002-9297",
- "date": "1998-11-01",
- "abstract": "Huntington disease (HD) is an autosomal dominant neurodegenerative disorder characterized by motor disturbance, cognitive loss, and psychiatric manifestations. The disease is associated with a CAG trinucleotide-repeat expansion in the Huntington gene (IT15) on chromosome 4p16.3. One family with a history of HD was referred to us initially for predictive testing using linkage analysis. However, the chromosome 4p region was completely excluded by polymorphic markers, and later no CAG-repeat expansion in the HD gene was detected. To map the disease trait segregating in this family, whole-genome screening with highly polymorphic dinucleotide-, trinucleotide-, and tetranucleotide-repeat DNA markers was performed. A positive LOD score of 3.01 was obtained for the marker D20S482 on chromosome 20p, by two-point LOD-score analysis with the MLINK program. Haplotype analysis indicated that the gene responsible for the disease is likely located in a 2.7-cM region between the markers D20S193 and D20S895. Candidate genes from the mapping region were screened for mutations.",
+ "publisher": "International journal of cancer",
+ "issn": "0020-7136",
+ "date": "2001-02-01",
+ "abstract": "The human epithelial mucin MUC1 is over-expressed in more than 90% of carcinomas of the breast, ovary, and pancreas as well as in some other tumours, making it a potential target for tumour immunotherapy. We have identified several MUC1-derived peptides mapping outside the variable number tandem repeat region that comply with the peptide-binding motif for HLA-A*0201 and that become processed into stable major histocompatibility complex-peptide complexes as assessed by in vitro assays. In A2/K(b) transgenic mice, 3 peptides, namely MUC(79-87) (TLAPATEPA), MUC(167-175) (ALGSTAPPV) and MUC(264-272) (FLSFHISNL) elicit peptide-specific cytotoxic T lymphocyte (CTL) immunity, which protects these mice against a challenge with MUC1, A2/K(b)-expressing tumour cells. These peptides therefore represent naturally processed MUC1-derived CTL epitopes that could be used as components in peptide-based vaccines and for the analysis of anti-MUC1 CTL responses in A*0201-positive patients with MUC1-expressing tumours.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9792871"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11169964"
},
{
- "id": "pmid:9647305",
+ "id": "pmid:10741704",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/9647305",
- "title": "Genetic polymorphisms adjacent to the CAG repeat influence clinical features at onset in Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/10741704",
+ "title": "Flow cytometric measurement of intracellular cytokines detects immune responses in MUC1 immunotherapy.",
"type": "article-journal",
- "doi": "10.1136/jnnp.64.6.758",
+ "doi": "",
"authors": [
- ["I", "Vuillaume"],
- ["P", "Vermersch"],
- ["A", "Dest\u00e9e"],
- ["H", "Petit"],
- ["B", "Sablonni\u00e8re"]
+ ["V", "Karanikas"],
+ ["J", "Lodding"],
+ ["V C", "Maino"],
+ ["I F", "McKenzie"]
],
- "publisher": "Journal of neurology, neurosurgery, and psychiatry",
- "issn": "0022-3050",
- "date": "1998-06-01",
- "abstract": "To evaluate possible influences of CCG and delta2642 glutamic acid polymorphisms adjacent to the (CAG)n trinucleotide repeat in Huntington's disease gene IT15 on some clinical features (age and symptoms) at onset.",
+ "publisher": "Clinical cancer research : an official journal of the American Association for Cancer Research",
+ "issn": "1078-0432",
+ "date": "2000-03-01",
+ "abstract": "The detection of tumor-specific T cells in immunized cancer patients usually relies on lengthy and difficult CTL assays; we now report on flow cytometry to detect the intracellular cytokines interleukin 2 (IL-2), IL-4, IFN-gamma, and tumor necrosis factor alpha (TNF-alpha) produced by CD4+CD69+ and CD8+CD69+ activated T cells after MUC1 antigen stimulation. Peripheral blood mononuclear cells were obtained from 12 patients with adenocarcinoma injected with mannan-MUC1; cells were exposed in vitro for 18 h to MUCI peptide in the presence of CD28 monoclonal antibody and Brefeldin; permeabilized cells were used for the expression of cytokines. After stimulation in vitro with MUC1-variable number of tandem repeats peptides, CD8+CD69+ T cells from all immunized patients generated 3-9 times higher levels of TNF-alpha(P < 0.038) and IFN-gamma (P <0.010) than did cells from 12 normal subjects; minor increases in IL-4 occurred. By contrast, CD4+CD69+ cells showed no overall alteration in TNF-alpha and IFN-gamma cytokine production, although in some patients, their measurement was informative; the measurement of IL-2 was not useful in either CD4+CD69+ or CD8+CD69+ cells. We conclude that in MUC1-immunized patients, the measurement of TNF-alpha and IFN-gamma in activated CD69+CD8+ T cells may be indicative of their immune status.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9647305"
-},
-{
- "id": "pmid:9626775",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/9626775",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:9626775']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10741704"
},
{
- "id": "pmid:9611675",
+ "id": "pmid:10653872",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/9611675",
- "title": "Serotonin transporter gene and risk for bipolar affective disorder: an association study in Spanish population.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/10653872",
+ "title": "Survival in early breast cancer patients is favorably influenced by a natural humoral immune response to polymorphic epithelial mucin.",
"type": "article-journal",
- "doi": "10.1016/s0006-3223(97)00540-4",
+ "doi": "10.1200/jco.2000.18.3.574",
"authors": [
- ["B", "Guti\u00e9rrez"],
- ["M J", "Arranz"],
- ["D A", "Collier"],
- ["V", "Vall\u00e8s"],
- ["R", "Guillamat"],
- ["J", "Bertranpetit"],
- ["R M", "Murray"],
- ["L", "F\u00e3n\u00e1s"]
+ ["S", "von Mensdorff-Pouilly"],
+ ["A A", "Verstraeten"],
+ ["P", "Kenemans"],
+ ["F G", "Snijdewint"],
+ ["A", "Kok"],
+ ["G J", "Van Kamp"],
+ ["M A", "Paul"],
+ ["P J", "Van Diest"],
+ ["S", "Meijer"],
+ ["J", "Hilgers"]
],
- "publisher": "Biological psychiatry",
- "issn": "0006-3223",
- "date": "1998-06-01",
- "abstract": "The serotonin transporter (5-HTT) is an important candidate gene for the genetic transmission of manic depressive illness. Many studies of patients with affective disorders have found abnormalities in serotonin metabolism and dysregulation of the transporter itself. In the present study, we hypothesize that genetic variation in the 5-HTT gene (17q11.1-17q12) may have an effect in the etiology of manic depression.",
+ "publisher": "Journal of clinical oncology : official journal of the American Society of Clinical Oncology",
+ "issn": "0732-183X",
+ "date": "2000-02-01",
+ "abstract": "Polymorphic epithelial mucin (PEM or MUC1) is being studied as a vaccine substrate for the immunotherapy of patients with adenocarcinoma. The present study analyzes the incidence of naturally occurring MUC1 antibodies in early breast cancer patients and relates the presence of these antibodies in pretreatment serum to outcome of disease.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9611675"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10653872"
},
{
- "id": "pmid:9536080",
+ "id": "pmid:10430099",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/9536080",
- "title": "Aggregation of N-terminal huntingtin is dependent on the length of its glutamine repeats.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/10430099",
+ "title": "Immunization of chimpanzees with tumor antigen MUC1 mucin tandem repeat peptide elicits both helper and cytotoxic T-cell responses.",
"type": "article-journal",
- "doi": "10.1093/hmg/7.5.777",
+ "doi": "",
"authors": [
- ["S H", "Li"],
- ["X J", "Li"]
+ ["S M", "Barratt-Boyes"],
+ ["A", "Vlad"],
+ ["O J", "Finn"]
],
- "publisher": "Human molecular genetics",
- "issn": "0964-6906",
- "date": "1998-05-01",
- "abstract": "Huntington's disease (HD) is caused by expansion of a glutamine repeat in huntingtin. Mutant huntingtin contains 36-55 repeats in adult HD patients and >60 repeats in juvenile HD patients. An N-terminal fragment of mutant huntingtin forms aggregates in neuronal nuclei in the brains of transgenic mice and HD patients. Aggregation of expanded polyglutamine is thought to be a common pathological mechanism in HD and other glutamine repeat diseases. It is not clear how the length of the repeats is correlated with formation of protein aggregates. By expressing a series of huntingtin constructs encoding various glutamine repeats (23-150 units) in cultured cells we observed N-terminal fragments of huntingtin (amino acids 1-67 and 1-212), but not full-length huntingtins, with glutamine repeats >/=66 units formed protein aggregates. Huntingtin aggregation was not induced when the repeat was /=120 units. This study suggests that various N-terminal fragments of mutant huntingtin can form aggregates and that aggregation is prompted by lengthening the glutamine repeat.",
+ "publisher": "Clinical cancer research : an official journal of the American Association for Cancer Research",
+ "issn": "1078-0432",
+ "date": "1999-07-01",
+ "abstract": "CTLs and antibody responses to the tumor-associated antigen MUC1 mucin can be detected in patients with adenocarcinomas of the breast, pancreas, colon, and ovary. However, neither response is generally effective at controlling disease. Methods to augment immunity to MUC1 are being designed, with the expectation that this will lead to an antitumor response. The key to eliciting potent immunity to tumor MUC1 may be in generating MUC1-specific T-helper cell responses, which, to date, have not been reported in cancer patients. We have recently demonstrated that a synthetic vaccine representing five copies of the MUC1 tandem repeat peptide can be used to prime MUC1-specific human CD4+ T cells in vitro. Here, we extend these studies to test the immunogenicity and safety of the tandem repeat peptide in the chimpanzee, which has the identical MUC1 tandem repeat sequence to the human. To promote induction of Th1-type responses, we used the novel adjuvant LeIF, a Leishmania-derived protein that is known to stimulate human peripheral blood mononuclear cells (PBMCs) and antigen-presenting cells, to produce a Th1-type cytokine profile. We found that MUC1 tandem repeat peptide administered with LeIF elicited positive, albeit transient, proliferative T-cell responses to MUC1 in the PBMCs from four of four chimpanzees. Immunization induced MUC1-specific IFN-gamma but not interleukin 4 expression in CD4+ T cells from PBMCs and draining lymph nodes. MUC1-specific CTLs were also generated that did not induce detectable autoimmune dysfunction during the 1 year of observation. We conclude that the MUC1 tandem repeat peptide can be used to elicit both T-helper and cytotoxic cell responses to MUC1 in the primate and holds promise as a safe and effective cancer vaccine.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9536080"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10430099"
},
{
- "id": "pmid:9595987",
+ "id": "pmid:10383817",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/9595987",
- "title": "1H NMR spectroscopy studies of Huntington's disease: correlations with CAG repeat numbers.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/10383817",
+ "title": "Presentation of MUC1 tumor antigen by class I MHC and CTL function correlate with the glycosylation state of the protein taken Up by dendritic cells.",
"type": "article-journal",
- "doi": "10.1212/wnl.50.5.1357",
+ "doi": "10.1006/cimm.1999.1512",
"authors": [
- ["B G", "Jenkins"],
- ["H D", "Rosas"],
- ["Y C", "Chen"],
- ["T", "Makabe"],
- ["R", "Myers"],
- ["M", "MacDonald"],
- ["B R", "Rosen"],
- ["M F", "Beal"],
- ["W J", "Koroshetz"]
+ ["E M", "Hiltbold"],
+ ["M D", "Alter"],
+ ["P", "Ciborowski"],
+ ["O J", "Finn"]
],
- "publisher": "Neurology",
- "issn": "0028-3878",
- "date": "1998-05-01",
- "abstract": "Huntington's disease (HD) is the result of an expanded (CAG) repeat in a gene on chromosome 4. A consequence of the gene defect may be progressive impairment of energy metabolism. We previously showed increased occipital cortex lactate in HD using localized 1H spectroscopy. We have now extended these studies to show an almost threefold elevation in occipital cortex lactate in 31 HD patients as compared with 17 normal control subjects (p < 10(-11)). The spectra in three presymptomatic gene-positive patients were identical to normal control subjects in cortical regions, but three in eight showed elevated lactate in the striatum. Similar to recently reported increases in task-related activation of the striatum in the dominant hemisphere, we found that striatal lactate levels in HD patients were markedly asymmetric (higher on the left side). Markers of neuronal degeneration, decreased N-acetylaspartate (NAA)/creatine and increased choline/creatine levels, were symmetric. Both decreased NAA and increased lactate in the striatum significantly correlated with duration of symptoms. When divided by his or her age, an individual's striatal NAA loss and lactate increase were found to directly correlate with the subject's CAG repeat number, with correlation coefficients of 0.8 and 0.7, respectively. Similar correlations were noted between postmortem cell loss and age versus CAG repeat length. Together, these data provide further evidence for an interaction between neuronal activation and a defect in energy metabolism in HD that may extend to presymptomatic subjects.",
+ "publisher": "Cellular immunology",
+ "issn": "0008-8749",
+ "date": "1999-06-15",
+ "abstract": "We previously reported that the glycosylated MUC1 tumor antigen circulating as soluble protein in patients' serum is not processed by dendritic cells and does not elicit MHC-Class II-restricted T helper responses in vitro. In contrast, a long synthetic peptide from the MUC1 tandem repeat region is presented by Class II molecules, resulting in the initiation of T helper cell responses. Here we addressed the ability of dendritic cells to present various glycosylated or not glycosylated forms of MUC1 by MHC Class I. We found that three different forms of MUC1, ranging from glycosylated and underglycosylated protein to unglycosylated synthetic peptide, were able to elicit MUC1-specific, Class-I-restricted CTL responses. The efficiency of processing and the resulting strength of CTL activity were inversely correlated with the degree of glycosylation of the antigen. Furthermore, the more efficiently processed 100mer peptide primed a broader repertoire of CTL than the glycosylated protein.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9595987"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10383817"
},
{
- "id": "pmid:9577843",
+ "id": "pmid:10235488",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/9577843",
- "title": "Role of serotonin transporter promoter repeat length polymorphism (5-HTTLPR) in seasonality and seasonal affective disorder.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/10235488",
+ "title": "Cellular and humoral immune responses to MUC1 mucin and tandem-repeat peptides in ovarian cancer patients and controls.",
"type": "article-journal",
- "doi": "10.1038/sj.mp.4000360",
+ "doi": "10.1007/s002620050547",
"authors": [
- ["N E", "Rosenthal"],
- ["C M", "Mazzanti"],
- ["R L", "Barnett"],
- ["T A", "Hardin"],
- ["E H", "Turner"],
- ["G K", "Lam"],
- ["N", "Ozaki"],
- ["D", "Goldman"]
+ ["F G", "Snijdewint"],
+ ["S", "von Mensdorff-Pouilly"],
+ ["A H", "Karuntu-Wanamarta"],
+ ["A A", "Verstraeten"],
+ ["I", "van Zanten-Przybysz"],
+ ["P", "Hummel"],
+ ["H W", "Nijman"],
+ ["P", "Kenemans"],
+ ["J", "Hilgers"]
],
- "publisher": "Molecular psychiatry",
- "issn": "1359-4184",
- "date": "1998-03-01",
- "abstract": "Seasonal variations in mood and behavior (seasonality) and seasonal affective disorder (SAD) have been attributed to seasonal fluctuations in brain serotonin (5-HT). the short (s), as opposed to the long (l), allele of the 5-HT transporter linked polymorphism (5-HTTLPR) has been associated with neuroticism and depression. We hypothesized that this short allele would also be associated with SAD and with higher levels of seasonality. Ninety-seven SAD patients and 71 non-seasonal healthy controls with low seasonality levels were genotyped for 5-HTTLPR and compared statistically. Patients with SAD were less likely to have the l/l genotype (27.8% vs 47.9%; P < 0.01) and more likely to have the s allele (44.8% vs 32.4%; P < 0.02) as compared to controls. The three 5-HTTLPR genotypes were also differentially distributed in patients and controls (P < 0.03). The SAD patients with the l/l genotype had a lower mean seasonality score than did patients with the other two genotypes (mean +/- s.d. = 15.3 +/- 2.8 vs 17.1 +/- 3.4 respectively; P < 0.02). The 5-HTTLPR short allele contributes to the trait of seasonality and is a risk factor for SAD, providing further evidence for a relationship between genetic variation in the 5-HT transporter (5-HTT) and behavior.",
+ "publisher": "Cancer immunology, immunotherapy : CII",
+ "issn": "0340-7004",
+ "date": "1999-04-01",
+ "abstract": "The objective of this study was to demonstrate the presence of proliferative T cell responses to human polymorphic epithelial mucin (MUC1) and its tandem-repeat peptides in peripheral blood mononuclear cells (PBMC) from ovarian cancer patients and from controls and to correlate these cellular responses to a humoral response to MUC1. PBMC were obtained from 6 healthy women, from 13 women in the third trimester of pregnancy and from 21 ovarian cancer patients. Only 1 of the 6 healthy women showed a weak primary proliferative response (stimulation index, SI <2) to a 20-mer MUC1 tandem-repeat peptide in the presence of interleukin-2 (IL-2). In PBMC from 5/13 pregnant women (38%) a weak response could be induced by the 20-mer and/or 60-mer tandem-repeat peptides (SI < or =3.0) and in PBMC from 8/15 ovarian cancer patients (53%) 20-mer and/or 60-mer MUC1 tandem-repeat peptides induced primary responses (SI < or =5.4). MUC1 mucin purified from a breast tumor cell line and/or from urine of a healthy donor had a relatively strong stimulating effect (SI < or =19) on PBMC from 4 of 16 ovarian cancer patients (25%). In contrast, in PBMC of 9 ovarian cancer patients stimulated by the addition of a Candida albicans extract, MUC1 mucin strongly inhibited proliferation. This inhibition could partially be abrogated by the addition of IL-2. MUC1 (CA 15.3 assay) and free circulating MUC1 IgG and IgM antibodies (PEM.CIg assay) were determined in the plasma of all subjects. The MUC1 and the free circulating MUC1 IgG antibody plasma levels were significantly higher in the ovarian cancer patients than in the healthy women. Although no significant correlations were found between MUC1 mucin, MUC1 Ab plasma levels and the individual proliferative responses to the MUC1 antigens, an association may exist between them, since all three are significantly higher in the ovarian cancer patients than in the healthy women.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9577843"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10235488"
},
{
- "id": "pmid:9485067",
+ "id": "pmid:10022471",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/9485067",
- "title": "[11C]raclopride-PET studies of the Huntington's disease rate of progression: relevance of the trinucleotide repeat length.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/10022471",
+ "title": "Isolation of MUC1-primed B lymphocytes from tumour-draining lymph nodes by immunomagnetic beads.",
"type": "article-journal",
- "doi": "10.1002/ana.410430216",
+ "doi": "10.1007/s002620050531",
"authors": [
- ["A", "Antonini"],
- ["K L", "Leenders"],
- ["D", "Eidelberg"]
+ ["C", "Petrarca"],
+ ["B", "Casalino"],
+ ["S", "von Mensdorff-Pouilly"],
+ ["A", "Rughetti"],
+ ["H", "Rahimi"],
+ ["G", "Scambia"],
+ ["J", "Hilgers"],
+ ["L", "Frati"],
+ ["M", "Nuti"]
],
- "publisher": "Annals of neurology",
- "issn": "0364-5134",
- "date": "1998-02-01",
- "abstract": "We used [11C]raclopride and positron emission tomography (PET) to assess the relationship between striatal dopamine D2 receptor binding, trinucleotide repeat number (CAG), and subject age in 10 asymptomatic and 8 symptomatic carriers of the Huntington's disease (HD) mutation. In both preclinical and symptomatic gene carriers, we found significant correlations between CAG repeat length and the ratio of percent loss in striatal D2 receptor binding divided by age. In accord with neuropathological studies, we obtained an intercept at 35.5 CAG repeats in the symptomatic HD patients. Nonetheless, we noted that the slopes of the correlation lines differed significantly for the presymptomatic and symptomatic cohorts. These PET results support the notion that the HD disease process is a function of trinucleotide length and age, and that the development of clinical signs and symptoms is associated with CAG repeat lengths greater than 35.5. However, our analysis also suggests that striatal degeneration may proceed in a nonlinear fashion. These findings have implications for the design of neuroprotective strategies for the treatment of HD.",
+ "publisher": "Cancer immunology, immunotherapy : CII",
+ "issn": "0340-7004",
+ "date": "1999-01-01",
+ "abstract": "The humoral immune response against a tumour-associated antigen, polymorphic epithelial mucin (PEM, MUC1) in cancer patients was studied by isolating specific B cells primed for the antigen. Human B lymphocytes from tumour-draining lymph nodes, obtained from 12 patients with epithelial cancers, were immunoselected with magnetic beads coated with a 60mer synthetic peptide corresponding to three tandem repeats of the protein core of the MUC1 antigen. Short-term cultures of B cells were established utilizing interleukin-10 (IL-10), IL-4 and monoclonal antibody anti-CD40, and were maintained for a maximum of 3 weeks. B cell culture supernatants contained human anti-MUC1 antibodies, as detected by enzyme-linked immunosorbent assay, in 6/12 of the patients tested. Five of these patients, all with early-stage cancer, also had high levels of circulating anti-MUC1 IgM antibodies in the serum. A significant correlation was found (two-tailed P = 0.041) between the presence of circulating anti-MUC1 antibodies and the ability to isolate PEM-specific B cells from tumour-draining lymph nodes. The technique proposed provides a useful method for the analysis of natural immunity against defined tumour antigens.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9485067"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10022471"
},
{
- "id": "pmid:9462548",
+ "id": "pmid:9755875",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/9462548",
- "title": "Instability of dinucleotide repeats in Hodgkin's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9755875",
+ "title": "Induction of HLA-unrestricted and HLA-class-II-restricted cytotoxic T lymphocytes against MUC-1 from patients with colorectal carcinomas using recombinant MUC-1 vaccinia virus.",
"type": "article-journal",
- "doi": "10.1002/(sici)1096-8652(199802)57:2<148::aid-ajh10>3.0.co;2-8",
+ "doi": "10.1007/s002620050500",
"authors": [
- ["Z", "Mark"],
- ["A", "Toren"],
- ["N", "Amariglio"],
- ["G", "Schiby"],
- ["F", "Brok-Simoni"],
- ["G", "Rechavi"]
+ ["J", "Akagi"],
+ ["K", "Nakagawa"],
+ ["H", "Egami"],
+ ["M", "Ogawa"]
],
- "publisher": "American journal of hematology",
- "issn": "0361-8609",
- "date": "1998-02-01",
- "abstract": "Tumorigenesis has been shown to proceed through a series of genetic alterations involving protooncogenes and tumor suppressor genes. However, the investigation of genomic instability of microsatellites has disclosed a new mechanism for human carcinogenesis, which is involved not only in hereditary nonpolyposis colon cancer (HNPCC) but in a number of other malignancies as well. To determine whether microsatellite instability is involved in Hodgkin's disease, we screened 16 such tumors using 7 microsatellite marker loci on 6 chromosome arms 4, 5, 9p, 9q, 11, 14, and 17. Using the polymerase chain reaction method, DNA samples from the tumors and from normal peripheral blood leukocytes from each patient were compared for the allelic pattern produced at each locus. Five cases of genomic instability were identified, suggesting that this mechanism is relevant to the pathogenesis of HD.",
+ "publisher": "Cancer immunology, immunotherapy : CII",
+ "issn": "0340-7004",
+ "date": "1998-09-01",
+ "abstract": "We recently reported that immunization with a recombinant MUC-1 vaccinia virus (rVMUC-1) protected C57BL/6 mice from challenge with DF3/MUC-1-positive syngeneic tumors. To elucidate whether anti-MUC-1 tumor immunity, especially MUC-1-specific cytotoxic T lymphocytes (CTI), can be induced in cancer patients by rVMUC-1, we stimulated the peripheral blood lymphocytes from patients with DF3/MUC-1+ or DF3/MUC-1 colon carcinomas using the autologous monocytes infected with rVMUC-1 (rVAMN). The stimulated T lymphocytes from two patients with DF3/MUC-1-positive colorectal carcinomas (rVPY+T and rVPW+T) demonstrated HLA-unrestricted cytotoxicity against MUC-1, whereas those from the patient with DF3/MUC-1-negative colon carcinoma (rVPA-T) did not. The HLA-unrestricted cytotoxicity was demonstrated by the CD8+ T cells possibly recognizing an epitope present on the tandem repeats. Adoptive immunotherapy who performed three times with patient PY, at 4-week intervals. The adoptive transfer of the first stimulated lymphocytes, demonstrating a high level of HLA-unrestricted cytotoxicity against MUC-1, resulted in the significant reduction of the liver metastasis of patient PY. However, HLA-unrestricted cytotoxicity against MUC-1 was extremely reduced at the second transfer and finally eliminated at the third, whereas the CD4+ T cells demonstrating HLA-class-II-restricted cytotoxicity against MUC-1 predominantly proliferated at the third adoptive immunotherapy treatment. The liver metastasis and the serum levels of tumor markers (carcinoembryonic antigen CA19-9) demonstrated a rapid and marked increment after the second transfer and especially after the third. These results suggest that the HLA-unrestricted cytotoxic CD8+ T cells against MUC-1, induced in patients with DF3/MUC-1+ colorectal carcinomas using rVMUC-1, correlate with the antitumor activity in vivo.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9462548"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9755875"
},
{
- "id": "pmid:23604331",
+ "id": "pmid:9591045",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23604331",
- "title": "Inhibition of \u03b1-ketoglutarate-and pyruvate dehydrogenase complexes in E. coli by a glutathione S-transferase containing a pathological length poly-Q domain: A possible role of energy deficit in neurological diseases associated with poly-Q expansions?",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9591045",
+ "title": "An enzyme-linked immunosorbent assay for the measurement of circulating antibodies to polymorphic epithelial mucin (MUC1).",
"type": "article-journal",
- "doi": "10.1007/s11357-998-0004-x",
+ "doi": "10.1159/000030006",
"authors": [
- ["A J", "Cooper"],
- ["K F", "Sheu"],
- ["J R", "Burke"],
- ["O", "Onodera"],
- ["W J", "Strittmatter"],
- ["A D", "Roses"],
- ["J P", "Blass"]
+ ["S", "von Mensdorff-Pouilly"],
+ ["M M", "Gourevitch"],
+ ["P", "Kenemans"],
+ ["A A", "Verstraeten"],
+ ["G J", "van Kamp"],
+ ["A", "Kok"],
+ ["K", "van Uffelen"],
+ ["F G", "Snijdewint"],
+ ["M A", "Paul"],
+ ["S", "Meijer"],
+ ["J", "Hilgers"]
],
- "publisher": "Age",
- "issn": "",
+ "publisher": "Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine",
+ "issn": "1010-4283",
"date": "1998-01-01",
- "abstract": "At least seven adult-onset neurodegenerative diseases, including Huntington's disease (HD), are caused by genes containing expanded CAG triplets within their coding regions. The expanded CAG repeats give rise to extended stretches of polyglutamines (Qn) in the proteins expressed by the affected genes. Generally, n \u226540 in affected individuals and \u226436 in clinically unaffected individuals. The expansion has been proposed to confer a \"toxic gain of function\" to the mutated protein. Poly-Q domains have recently been shown to be excellent substrates of tissue transglutaminase. We investigated the effects of expression of glutathione S-transferase constructs containing poly-Q inserts of various lengths (GSTQn where n = 0, 10, 62 or 81) on the activity of some key metabolic enzymes in the host Escherischia coil-an organism not known to have transglutaminase activity. E. coil carrying the GSTQ62 construct exhibited statistically significant decreases in the specific activities of \u03b1-ketoglutarate dehydrogenase complex (KGDHC) and pyruvate dehydrogenase complex (PDHC). Previous work has shown that KGDHC and PDHC activities are reduced in the brains of Alzheimer's disease (AD) patients. Our results suggest that KGDHC and PDHC may be particularly susceptible to the effects of a number of disparate insults, including those associated with AD and HD.",
+ "abstract": "About one-third of breast and ovarian carcinoma patients have circulating antibodies reactive with polymorphic epithelial mucin (MUC1), either free or bound to immune complexes. While the presence of these immune complexes has prognostic significance in breast cancer patients, the significance of free MUC1 antibodies is less clear. The objective of this study was to develop a reliable assay for the accurate determination of circulating free antibodies to MUC1.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23604331"
-},
-{
- "id": "pmid:9339688",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/9339688",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:9339688']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9591045"
},
{
- "id": "pmid:9299885",
+ "id": "pmid:9575675",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/9299885",
- "title": "Analysis of the (CAG)n repeat at the IT15 locus in a population from Calabria (southern Italy).",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9575675",
+ "title": "A large number of tandem repeats in the polymorphic epithelial mucin gene is associated with severe acne.",
"type": "article-journal",
- "doi": "",
+ "doi": "10.1111/j.1346-8138.1998.tb02370.x",
"authors": [
- ["O", "Leone"],
- ["M", "Muglia"],
- ["A L", "Gabriele"],
- ["G", "Annesi"],
- ["F L", "Conforti"],
- ["E", "Imbrogno"],
- ["L", "Imbrogno"],
- ["C", "Brancati"]
+ ["I", "Ando"],
+ ["A", "Kukita"],
+ ["G", "Soma"],
+ ["H", "Hino"]
],
- "publisher": "Human biology",
- "issn": "0018-7143",
- "date": "1997-10-01",
- "abstract": "The defect causing Huntington's disease (HD) has recently been discovered as an expanded CAG trinucleotide repeat located at the 5' end of the IT15 gene. This discovery allows the molecular diagnosis of HD by measuring the CAG repeat length. The normal and pathological repeat ranges in a population need to be established before a diagnostic test for HD can be performed. To determine the distribution of IT15 alleles in a population from Calabria (southern Italy), we analyzed 102 normal subjects and 9 HD patients coming from a defined area of Calabria (province of Cosenza). Expanded alleles ranged from 44 to 76 repeats. Normal alleles varied from 8 to 27 repeats, which is one of the lowest values observed at the top of the normal range; the mean was significantly different from the value observed in six other populations. The allele distribution seemed to group mainly around the mode, and no intermediate alleles were present in our sample. These results suggest a particular stability of the CAG repeat at the IT15 locus in the Calabrian group and confirm once again the peculiar genetic structure of this population.",
+ "publisher": "The Journal of dermatology",
+ "issn": "0385-2407",
+ "date": "1998-03-01",
+ "abstract": "Polymorphic epithelial mucin (PEM) or MUC1 is a glycoprotein secreted from various epithelial gland tissues. In skin, PEM is detected in sweat glands and sebaceous glands by the DF3 monoclonal antibody. The gene of PEM includes an allele exhibiting length polymorphism due to a variable number of tandem repeats (VNTR); this is expressed co-dominantly, which may influence the microenvironment of the skin. The allelic size variation of the PEM gene was investigated in Japanese acne patients, atopic dermatitis patients, and healthy controls. The frequency of longer length alleles was significantly higher in severe acne patients.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9299885"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9575675"
},
{
- "id": "pmid:9267034",
+ "id": "pmid:9551361",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/9267034",
- "title": "Huntingtin-encoded polyglutamine expansions form amyloid-like protein aggregates in vitro and in vivo.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9551361",
+ "title": "Cyclophosphamide enhances the CTL precursor frequency in mice immunized with MUC1-mannan fusion protein (M-FP).",
"type": "article-journal",
- "doi": "10.1016/s0092-8674(00)80514-0",
+ "doi": "10.1097/00002371-199803000-00003",
"authors": [
- ["E", "Scherzinger"],
- ["R", "Lurz"],
- ["M", "Turmaine"],
- ["L", "Mangiarini"],
- ["B", "Hollenbach"],
- ["R", "Hasenbank"],
- ["G P", "Bates"],
- ["S W", "Davies"],
- ["H", "Lehrach"],
- ["E E", "Wanker"]
+ ["V", "Apostolopoulos"],
+ ["V", "Popovski"],
+ ["I F", "McKenzie"]
],
- "publisher": "Cell",
- "issn": "0092-8674",
- "date": "1997-08-08",
- "abstract": "The mechanism by which an elongated polyglutamine sequence causes neurodegeneration in Huntington's disease (HD) is unknown. In this study, we show that the proteolytic cleavage of a GST-huntingtin fusion protein leads to the formation of insoluble high molecular weight protein aggregates only when the polyglutamine expansion is in the pathogenic range. Electron micrographs of these aggregates revealed a fibrillar or ribbon-like morphology, reminiscent of scrapie prions and beta-amyloid fibrils in Alzheimer's disease. Subcellular fractionation and ultrastructural techniques showed the in vivo presence of these structures in the brains of mice transgenic for the HD mutation. Our in vitro model will aid in an eventual understanding of the molecular pathology of HD and the development of preventative strategies.",
+ "publisher": "Journal of immunotherapy (Hagerstown, Md. : 1997)",
+ "issn": "1524-9557",
+ "date": "1998-03-01",
+ "abstract": "We have previously described the induction of murine CD8+ major histocompatibility complex class I restricted cytotoxic T cells to the 20 amino acid repeat region of human Mucin 1 (MUC1) variable number of tandem repeats region--a mucin greatly increased in expression in breast cancer and proposed as a target for immunotherapy. Mannan-MUC1 immunization protocol induces a high cytotoxic T lymphocyte (CTL) frequency, and some protection of mice against a tumor challenge. The CTL frequency can be substantially increased using cyclophosphamide (Cy), from 1/84,900 without Cy to 1/8,100 with Cy. Furthermore, in the presence of Cy, established tumors are rapidly eradicated, which does not happen in its absence. Cy clearly gives a major increase in the frequency of CTL precursors (CTLp) to MUC1 and could be of therapeutic value in patients.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9267034"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9551361"
},
{
- "id": "pmid:9150168",
+ "id": "pmid:8967520",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/9150168",
- "title": "The likelihood of being affected with Huntington disease by a particular age, for a specific CAG size.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/8967520",
+ "title": "Regulation of MUC5 and MUC1 gene expression: correlation with airway mucous differentiation.",
"type": "article-journal",
- "doi": "",
+ "doi": "10.1152/ajplung.1996.270.5.l846",
"authors": [
- ["R R", "Brinkman"],
- ["M M", "Mezei"],
- ["J", "Theilmann"],
- ["E", "Almqvist"],
- ["M R", "Hayden"]
+ ["K", "Guzman"],
+ ["T", "Bader"],
+ ["P", "Nettesheim"]
],
- "publisher": "American journal of human genetics",
- "issn": "0002-9297",
- "date": "1997-05-01",
- "abstract": "Prior studies describing the relationship between CAG size and the age at onset of Huntington disease (HD) have focused on affected persons. To further define the relationship between CAG repeat size and age at onset of HD, we now have analyzed a large cohort of affected and asymptomatic at-risk persons with CAG expansion. This cohort numbered 1,049 persons, including 321 at-risk and 728 affected individuals with a CAG size of 29-121 repeats. Kaplan-Meier analysis has provided curves for determining the likelihood of onset at a given age, for each CAG repeat length in the 39-50 range. The curves were significantly different (P < .0005), with relatively narrow 95% confidence intervals (95% CI) (+/-10%). Penetrance of the mutation for HD also was examined. Although complete penetrance of HD was observed for CAG sizes of > or = 42, only a proportion of those with a CAG repeat length of 36-41 showed signs or symptoms of HD within a normal life span. These data provide information concerning the likelihood of being affected, by a specific age, with a particular CAG size, and they may be useful in predictive-testing programs and for the design of clinical trials for persons at increased risk for HD.",
+ "publisher": "The American journal of physiology",
+ "issn": "0002-9513",
+ "date": "1996-05-01",
+ "abstract": "The purpose of this paper was to obtain probes to study the structure and function of mucins in rat models of airway cell differentiation and disease. We report the isolation and characterization of the rat cDNA homologue of the human airway secretory mucin, MUC5. Furthermore, we demonstrate the coordinate regulation of the expression of MUC5 and MUC1 (a membrane-bound mucin) and mucous differentiation. The rat MUC5 was cloned by the RT-PCR using motifs conserved in the secretory mucins, MUC2 and MUC5. The rat cDNA revealed a high degree of sequence similarity to human MUC5 (73% at the amino acid level). Alignments with three other secretory mucins (human MUC5, human MUC2, rat MUC2), indicated a conservation of the cysteines and of the octapeptide motifs, but a lack of conservation of a short tandem repeat sequence that is found only in the human MUC5. Northern analysis of MUC1 and MUC5 indicated a specific tissue-restricted pattern of expression. Surprisingly, rat MUC5 exhibited a monodisperse signal, a characteristic that is unusual for most secretory mucins, including the human MUC5. Expression of MUC1 and MUC5 correlated with mucous differentiation. Both genes were expressed at undetectable or very low levels in undifferentiated cultures, but both mucins became strongly expressed during mucous differentiation. Furthermore, neither mucin gene was expressed in retinoid-deficient cultures that undergo squamous instead of mucous differentiation. These studies demonstrate that expression of MUC1 and MUC5 is coordinately regulated with airway mucous cell differentiation. These cDNAs should provide useful tools to study mucin synthesis during differentiation and disease.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9150168"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8967520"
},
{
- "id": "pmid:9108071",
+ "id": "pmid:7594478",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/9108071",
- "title": "Genotypes at the GluR6 kainate receptor locus are associated with variation in the age of onset of Huntington disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/7594478",
+ "title": "Identification of an HLA-A11-restricted epitope from the tandem repeat domain of the epithelial tumor antigen mucin.",
"type": "article-journal",
- "doi": "10.1073/pnas.94.8.3872",
+ "doi": "",
"authors": [
- ["D C", "Rubinsztein"],
- ["J", "Leggo"],
- ["M", "Chiano"],
- ["A", "Dodge"],
- ["G", "Norbury"],
- ["E", "Rosser"],
- ["D", "Craufurd"]
+ ["N", "Dom\u00e9nech"],
+ ["R A", "Henderson"],
+ ["O J", "Finn"]
],
- "publisher": "Proceedings of the National Academy of Sciences of the United States of America",
- "issn": "0027-8424",
- "date": "1997-04-15",
- "abstract": "Huntington disease (HD) is associated with abnormal expansions of a CAG repeat close to the 5' end of the IT15 gene. We have assembled a set of 293 HD subjects whose ages of onset were known and sized their HD CAG repeats. These repeats accounted for 69% of the variance of age of onset when we used the most parsimonious model, which relates the logarithm of age of onset to a function of CAG repeat number. Since other familial factors have been proposed to influence the age of onset of HD, we have examined a number of candidate loci. The CAG repeat number on normal chromosomes, the delta2642 polymorphism in the HD gene, and apolipoprotein E genotypes did not affect the age of onset of HD. Although mitochondrial energy production defects in HD have led to suggestions that variants in the mitochondrial genome may be associated with clinical variability in HD, this suggestion was not supported by our preliminary experiments that examined the DdeI mitochondrial restriction fragment length polymorphism at position 10,394. Excitotoxicity has been a favored mechanism to explain the cell death in HD, particularly since intrastriatal injection of excitatory amino acids in animals creates HD-like pathology. Accordingly, we investigated the GluR6 kainate receptor. Of the variance in the age of onset of HD that was not accounted for by the CAG repeats, 13% could be attributed to GluR6 genotype variation. These data implicate GluR6-mediated excitotoxicity in the pathogenesis of HD and highlight the potential importance of this process in other polyglutamine repeat expansion diseases.",
+ "publisher": "Journal of immunology (Baltimore, Md. : 1950)",
+ "issn": "0022-1767",
+ "date": "1995-11-15",
+ "abstract": "Epithelial cell mucin encoded by the MUC-1 gene is overexpressed and aberrantly glycosylated on pancreatic, breast, and ovarian cancers as well as on multiple myelomas. It is recognized by patients' Ab and by T cells derived from tumor-draining lymph nodes. The T cell recognition is not MHC restricted and is specific for an epitope previously localized to the immunodominant tandem repeat region of the native mucin molecule. In search of possible MHC-restricted epitopes in the same immunodominant region, we synthesized a panel of overlapping, nine-amino acid long peptides spanning the MUC-1 tandem repeat and first examined their binding to specific human MHC class I molecules using two independent flow cytometry-based assay systems. This approach identified one peptide, p9-17 (STAPPAHGV), that bound to HLA-A1, -A2.1, -A3, and -A11. Measurements of the affinity of binding to each of these alleles, using a quantitative molecular binding assay, indicated that only the relative binding affinity to HLA-A11 was close to immunogenic values. We tested the immunogenicity of p9-17 in vitro. We detected a secondary T cell response specific for p9-17 in lymph nodes from an HLA-A11 breast cancer patient. Moreover, CTL specific for p9-17 peptide could be generated from PBL in several healthy HLA-A11 donors by primary in vitro stimulation.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9108071"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7594478"
},
{
- "id": "pmid:9106534",
+ "id": "pmid:8579785",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/9106534",
- "title": "Different mechanisms underlie DNA instability in Huntington disease and colorectal cancer.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/8579785",
+ "title": "Structure of a tumor associated antigen containing a tandemly repeated immunodominant epitope.",
"type": "article-journal",
- "doi": "",
+ "doi": "10.1080/07391102.1995.10508837",
"authors": [
- ["G M", "Goellner"],
- ["D", "Tester"],
- ["S", "Thibodeau"],
- ["E", "Almqvist"],
- ["Y P", "Goldberg"],
- ["M R", "Hayden"],
- ["C T", "McMurray"]
+ ["J D", "Fontenot"],
+ ["S V", "Mariappan"],
+ ["P", "Catasti"],
+ ["N", "Domenech"],
+ ["O J", "Finn"],
+ ["G", "Gupta"]
],
- "publisher": "American journal of human genetics",
- "issn": "0002-9297",
- "date": "1997-04-01",
- "abstract": "Two recent lines of evidence raise the possibility that instability in germ-line or somatic cells arises by a common mechanism that involves defective mismatch repair. Mutations in mismatch-repair proteins are known to cause instability in hereditary nonpolyposis colorectal cancer, instability that is physically similar to germ-line instability observed in Huntington disease (HD). Furthermore, both germ-line and somatic-cell instability are likely to be mitotic defects, the former occurring early in embryogenesis. To test the hypothesis that defective repair is a common prerequisite for instability, we have utilized two disease groups that represent different instability \"conditions.\" Germ-line instability within simple tandem repeats (STR) at 10 loci in 29 HD families were compared with somatic instability at the same loci in 26 colon cancer (CC) patients with identified or suspected defects in mismatch-repair enzymes. HD is known to be caused by expansion within the CAG repeat of the locus, but the extent or pattern of STR instability outside this region has not been examined systematically. We find a distinctly different pattern of STR mutation in the two disease groups, suggesting different mechanisms. Instability in HD is generally confined to a single locus, whereas instability is widespread for the same loci in CC. Our data do not support a causative role for defective mismatch-repair enzymes in instability associated with HD; rather, our data are consistent with a model in which DNA structure may inhibit normal mismatch repair at the expansion site.",
+ "publisher": "Journal of biomolecular structure & dynamics",
+ "issn": "0739-1102",
+ "date": "1995-10-01",
+ "abstract": "Human mucins are T or S glycosylated tandem repeat proteins. In breast cancer, mucins become under or unglycosylated. Two-dimensional nuclear magnetic resonance experiments are performed on chemically synthesized mucin tandem repeat polypeptides, (PDTRPAPGST-APPAHGVTSA)n the unglycosylated form for n=1,3 where (APDTR) constitutes the antigenic sites for the antibodies isolated form the tumors in the breast cancer patients. These studies demonstrate how the tandem repeats assemble in space giving rise to the overall tertiary structure, and the local structure and presentation of the antigenic site(APDTR) at the junction of two neighboring repeats. The NMR data reveal repeating knob-like structures connected by extended spacers. The knobs protrude away from the long-axis of Muc-1 and the predominant antigenic site (APDTR) forms the accessible tip of the knob. Multiple tandem repeats enhance the rigidity and presentation of the knob-like structures.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9106534"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8579785"
},
{
- "id": "pmid:9002673",
+ "id": "pmid:7946402",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/9002673",
- "title": "Trinucleotide repeats in the human genome: size distributions for all possible triplets and detection of expanded disease alleles in a group of Huntington disease individuals by the repeat expansion detection method.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/7946402",
+ "title": "Quantitation of mucin mRNA in respiratory and intestinal epithelial cells.",
"type": "article-journal",
- "doi": "10.1093/hmg/6.1.77",
+ "doi": "10.1165/ajrcmb.11.6.7946402",
"authors": [
- ["S", "Hofferbert"],
- ["N C", "Schanen"],
- ["F", "Chehab"],
- ["U", "Francke"]
+ ["J A", "Voynow"],
+ ["M C", "Rose"]
],
- "publisher": "Human molecular genetics",
- "issn": "0964-6906",
- "date": "1997-01-01",
- "abstract": "Using a modified Repeat Expansion Detection (RED) assay, that was optimized for individual oligonucleotides, unrelated individuals were systematically screened for maximal repeat sizes of each of the ten possible trinucleotide repeats. Cloned trinucleotide repeats were generated and used as standards for the detectability of single copy trinucleotide repeat fragments. When the size distributions of trinucleotide repeats were compared to previously reported data, significant differences were found for the CTT repeat, which corresponds to the expanded GAA repeat in Friedreich ataxia, as well as for ATT, CCT and GTT repeats. Since 30-35% of normal individuals have CTG/CAG trinucleotide repeat sizes of 180 bp or more, we investigated the question whether small-scale CTG/CAG repeat expansions are detectable on a population basis by using the RED technique. We blindly screened 20 HD probands with CAG expansions of the HD gene, ranging in size between 120 and 174 bp, and found that a shift to larger CAG size ranges is clearly detectable when comparing the distribution of maximal repeat sizes in the disease group to a control group. Our study, therefore, demonstrates that the application of the RED assay to a population of probands and a population of controls allows the detection of small-scale CTG/CAG repeat expansions in the size range of the expanded HD gene and present in a single allele. We also provide standards and control data for the detection of other trinucleotide repeat expansions.",
+ "publisher": "American journal of respiratory cell and molecular biology",
+ "issn": "1044-1549",
+ "date": "1994-12-01",
+ "abstract": "Mucin glycoproteins (mucins) are the major macromolecular constituents of mucus gels in mammalian respiratory, gastrointestinal, and reproductive tracts. Disorders of mucin glycosylation, which may result from either abnormal post-translational processing or differences in mucin protein gene expression, have been indicated in several diseases. Quantitation of mucin gene expression has been hindered by two features of human mucin genes: variable numbers of tandemly repeating nucleotides per mRNA molecule and polydisperse mRNA transcripts. We report here a method to quantitate mucin mRNA levels in epithelial cells and have evaluated three mucin genes, MUC1, MUC2, and MUC5, which are expressed in respiratory epithelium. The method uses the 3' non-tandem repeat mucin cDNA sequences, as they were shown to have a single-size transcript when amplified by the polymerase chain reaction, consistent with a one-to-one relationship with the mRNA molecule. The 3' non-tandem repeat cDNA sequences were cloned and transcribed in vitro to prepare complementary RNA (cRNA) standards. By comparison to a cRNA standard curve, mucin gene expression was evaluated in colon adenocarcinoma, pancreatic adenocarcinoma, and transformed respiratory epithelial cells and in nasal polyp tissue by slot blot analysis. CFPAC-1, a pancreatic adenocarcinoma cell line, expressed the highest MUC1 transcript levels. Colon adenocarcinoma cell lines varied in MUC2 expression levels, and one colon adenocarcinoma cell line, HT-29, had higher levels of MUC5 than MUC2. Nasal polyp tissue expressed more MUC5 mRNA than MUC1 or MUC2 mRNA. This mucin mRNA slot blot method provides a quantitative method for investigating the regulation of mucin gene expression in health and disease.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9002673"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7946402"
},
{
- "id": "pmid:9384710",
+ "id": "pmid:7514493",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/9384710",
- "title": "Polymorphism within the second intron of the IL-1 receptor antagonist gene in patients with hematopoietic malignancies.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/7514493",
+ "title": "Humoral immunity against a tandem repeat epitope of human mucin MUC-1 in sera from breast, pancreatic, and colon cancer patients.",
"type": "article-journal",
"doi": "",
"authors": [
- ["J", "Demeter"],
- ["G", "Messer"],
- ["S", "R\u00e4misch"],
- ["J B", "Mee"],
- ["F S", "di Giovine"],
- ["M", "Schmid"],
- ["F", "Herrmann"],
- ["F", "Porzsolt"]
+ ["Y", "Kotera"],
+ ["J D", "Fontenot"],
+ ["G", "Pecher"],
+ ["R S", "Metzgar"],
+ ["O J", "Finn"]
],
- "publisher": "Cytokines and molecular therapy",
- "issn": "1355-6568",
- "date": "1996-12-01",
- "abstract": "Alleles of the IL-1 genes are associated with several autoimmune and inflammatory diseases, where they tend to have a role in the severity of the disease rather than in susceptibility to the disease itself. Allele 2 of the variable number tandem repeat (VNTR) polymorphism in the IL-1 receptor antagonist (IL-1ra) gene was the first marker of the IL-1 cluster to be associated in this way with severity of chronic, systemic and local inflammatory diseases. Because of the role that IL-1 also plays in the pathobiology of certain hematopoietic disorders, we aimed at examining the allelic distribution of the IL-1ra VNTR in leukemias, lymphomas and related malignancies. While in patients with chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL), multiple myeloma (MM) and related disorders, primary acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and Hodgkin's disease (HD), the allelic distribution of IL-1RN was comparable to that seen in healthy control subjects, in a small group of patients with secondary AML the frequency of the IL-1RN*4 allele appeared to be significantly increased.",
+ "publisher": "Cancer research",
+ "issn": "0008-5472",
+ "date": "1994-06-01",
+ "abstract": "Using synthetic peptides 60,80, and 105 residues long, corresponding to 3, 4, and 5.25 tandem repeats of human mucin MUC-1 protein core, as antigens in a solid-phase enzyme-linked immunosorbent assay, we screened sera from 24 breast cancer patients, 10 colon cancer patients, and 12 pancreatic cancer patients, at various stages of disease, for the presence of mucin-specific antibodies. The 105-residue peptide was superior in allowing detection of high levels of anti-mucin antibodies in 10.9% of sera in each cancer group. Another 4.3% showed intermediate reactivity. Lower levels of detection were achieved with the 80-residue peptide, and no specific reactivity was detectable with the 60-residue peptide. Anti-mucin antibodies were previously undetectable when this assay was performed with purified whole mucin or short synthetic peptides. The presence or absence of antibody did not correlate with the levels of circulating mucin or stage of disease. One highly reactive serum sample was used to identify more precisely the epitope on the long synthetic peptide to which the reactivity was directed. The reactivity of this serum specific for the 105-residue peptide was blocked by a 9-residue peptide from the NH2-terminal region of the 20-residue tandem repeat containing the previously identified immunogenic epitope APDTRP. Another 9-residue mucin peptide, from the COOH-terminal region of the tandem repeat which does not contain the APDTRP epitope, had no effect. All the mucin-specific reactivity was found to be of the IgM isotype, indicating a helper T-cell-independent response, unusual for an antibody against a peptide epitope, but not unexpected for tandemly repeated epitopes.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9384710"
-},
-{
- "id": "pmid:8931689",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/8931689",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:8931689']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7514493"
},
{
- "id": "pmid:8751857",
+ "id": "pmid:21419568",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/8751857",
- "title": "CAG trinucleotide RNA repeats interact with RNA-binding proteins.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21419568",
+ "title": "Expansion of the phenotypic spectrum of SPG6 caused by mutation in NIPA1.",
"type": "article-journal",
- "doi": "",
+ "doi": "10.1016/j.clineuro.2011.02.011",
"authors": [
- ["B A", "McLaughlin"],
- ["C", "Spencer"],
- ["J", "Eberwine"]
+ ["Juan", "Du"],
+ ["Ya-Cen", "Hu"],
+ ["Bei-Sha", "Tang"],
+ ["Chong", "Chen"],
+ ["Ying-Ying", "Luo"],
+ ["Zi-Xiong", "Zhan"],
+ ["Guo-Hua", "Zhao"],
+ ["Hong", "Jiang"],
+ ["Kun", "Xia"],
+ ["Lu", "Shen"]
],
- "publisher": "American journal of human genetics",
- "issn": "0002-9297",
- "date": "1996-09-01",
- "abstract": "Genes associated with several neurological diseases are characterized by the presence of an abnormally long trinucleotide repeat sequence. By way of example, Huntington's disease (HD), is characterized by selective neuronal degeneration associated with the expansion of a polyglutamine-encoding CAG tract. Normally, this CAG tract is comprised of 11-34 repeats, but in HD it is expanded to > 37 repeats in affected individuals. The mechanism by which CAG repeats cause neuronal degeneration is unknown, but it has been speculated that the expansion primarily causes abnormal protein functioning, which in turn causes HD pathology. Other mechanisms, however, have not been ruled out. Interactions between RNA and RNA-binding proteins have previously been shown to play a role in the expression of several eukaryotic genes. Herein, we report the association of cytoplasmic proteins with normal length and extended CAG repeats, using gel shift and UV crosslinking assays. Cytoplasmic protein extracts from several rat brain regions, including the striatum and cortex, sites of neuronal degeneration in HD, contain a 63-kD RNA-binding protein that specifically interacts with these CAG-repeat sequences. These protein-RNA interactions are dependent on the length of the CAG repeat, with longer repeats binding substantially more protein. Two CAG repeat-binding proteins are present in human cortex and striatum; one comigrates with the rat protein at 63 kD, while the other migrates at 49 kD. These data suggest mechanisms by which RNA-binding proteins may be involved in the pathological course of trinucleotide repeat-associated neurological diseases.",
+ "publisher": "Clinical neurology and neurosurgery",
+ "issn": "1872-6968",
+ "date": "2011-03-17",
+ "abstract": "Hereditary spastic paraplegia type 6 (SPG6) is caused by mutations in the NIPA1 gene, this is a rare cause of HSP, until now, all the affected individuals reported displayed \"pure\" spastic paraplegia.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8751857"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21419568"
},
{
- "id": "pmid:8659522",
+ "id": "pmid:9736780",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/8659522",
- "title": "Phenotypic characterization of individuals with 30-40 CAG repeats in the Huntington disease (HD) gene reveals HD cases with 36 repeats and apparently normal elderly individuals with 36-39 repeats.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9736780",
+ "title": "CAG repeat expansion in autosomal dominant familial spastic paraparesis: novel expansion in a subset of patients.",
"type": "article-journal",
- "doi": "",
+ "doi": "10.1093/hmg/7.11.1779",
"authors": [
- ["D C", "Rubinsztein"],
- ["J", "Leggo"],
- ["R", "Coles"],
- ["E", "Almqvist"],
- ["V", "Biancalana"],
- ["J J", "Cassiman"],
- ["K", "Chotai"],
- ["M", "Connarty"],
- ["D", "Crauford"],
- ["A", "Curtis"],
- ["D", "Curtis"],
- ["M J", "Davidson"],
- ["A M", "Differ"],
- ["C", "Dode"],
- ["A", "Dodge"],
- ["M", "Frontali"],
- ["N G", "Ranen"],
- ["O C", "Stine"],
- ["M", "Sherr"],
- ["M H", "Abbott"],
- ["M L", "Franz"],
- ["C A", "Graham"],
- ["P S", "Harper"],
- ["J C", "Hedreen"],
- ["M R", "Hayden"]
+ ["K F", "Benson"],
+ ["M", "Horwitz"],
+ ["J", "Wolff"],
+ ["K", "Friend"],
+ ["E", "Thompson"],
+ ["S", "White"],
+ ["R I", "Richards"],
+ ["W H", "Raskind"],
+ ["T D", "Bird"]
],
- "publisher": "American journal of human genetics",
- "issn": "0002-9297",
- "date": "1996-07-01",
- "abstract": "Abnormal CAG expansions in the IT-15 gene are associated with Huntington disease (HD). In the diagnostic setting it is necessary to define the limits of the CAG size ranges on normal and HD-associated chromosomes. Most large analyses that defined the limits of the normal and pathological size ranges employed PCR assays, which included the CAG repeats and a CCG repeat tract that was thought to be invariant. Many of these experiments found an overlap between the normal and disease size ranges. Subsequent findings that the CCG repeats vary by 8 trinucleotide lengths suggested that the limits of the normal and disease size ranges should be reevaluated with assays that exclude the CCG polymorphism. Since patients with between 30 and 40 repeats are rare, a consortium was assembled to collect such individuals. All 178 samples were reanalyzed in Cambridge by using assays specific for the CAG repeats. We have optimized methods for reliable sizing of CAG repeats and show cases that demonstrate the dangers of using PCR assays that include both the CAG and CCG polymorphisms. Seven HD patients had 36 repeats, which confirms that this allele is associated with disease. Individuals without apparent symptoms or signs of HD were found at 36 repeats (aged 74, 78, 79, and 87 years), 37 repeats (aged 69 years), 38 repeats (aged 69 and 90 years), and 39 repeats (aged 67, 90, and 95 years). The detailed case histories of an exceptional case from this series will be presented: a 95-year-old man with 39 repeats who did not have classical features of HD. The apparently healthy survival into old age of some individuals with 36-39 repeats suggests that the HD mutation may not always be fully penetrant.",
+ "publisher": "Human molecular genetics",
+ "issn": "0964-6906",
+ "date": "1998-10-01",
+ "abstract": "Autosomal dominant familial spastic paraplegia (FSP) is a genetically heterogeneous neurodegenerative disorder displaying anticipation for which three loci have been mapped to the chromosomal positions 14q11.2-q24.3 (SPG3), 2p21-p24 (SPG4) and 15q11.1 (SPG6). The repeat expansion detection (RED) method has been used to demonstrate expanded CAG repeats in some FSP families that map to SPG4. We analyzed 20 FSP families, including four for which there is evidence for linkage to SPG4, and found that in most cases the repeat expansion detected by RED is due to non-pathogenic expansions of the chromosome 18q21.1 SEF2-1 or 17q21.3 ERDA1 locus. Polymorphic expansions at SEF2-1 and ERDA1 appear frequent and may confound RED studies in the search for genes causing disorders demonstrating anticipation. In six FSP families, however, CAG repeat expansion was detected in a subset of affected and at-risk individuals that did not result from expansion of the SEF2-1 and ERDA1 loci. Overall, 11 of 37 (30%) of the FSP patients with a CAG/CTG repeat expansion are unaccounted for by the SEF2-1 and ERDA1 loci, compared with two of 23 (9%) of the unaffected at-risk individuals and none of 19 controls. In the majority of cases these novel expansions were shorter than those previously reported.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8659522"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9736780"
},
{
- "id": "pmid:8735227",
+ "id": "pmid:40015643",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/8735227",
- "title": "Reduction in enkephalin and substance P messenger RNA in the striatum of early grade Huntington's disease: a detailed cellular in situ hybridization study.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/40015643",
+ "title": "Dissecting the mechanism of NOP56 GGCCUG repeat-associated non-AUG translation using cell-free translation systems.",
"type": "article-journal",
- "doi": "10.1016/0306-4522(95)00595-1",
+ "doi": "10.1016/j.jbc.2025.108360",
"authors": [
- ["S J", "Augood"],
- ["R L", "Faull"],
- ["D R", "Love"],
- ["P C", "Emson"]
+ ["Mayuka", "Hasumi"],
+ ["Hayato", "Ito"],
+ ["Kodai", "Machida"],
+ ["Tatsuya", "Niwa"],
+ ["Tomoya", "Taminato"],
+ ["Yoshitaka", "Nagai"],
+ ["Hiroaki", "Imataka"],
+ ["Hideki", "Taguchi"]
],
- "publisher": "Neuroscience",
- "issn": "0306-4522",
- "date": "1996-06-01",
- "abstract": "The expression of enkephalin and substance P messenger RNAs was examined in the caudate-putamen of human post mortem tissue from control and Huntington's disease tissue using in situ hybridization techniques and human specific enkephalin and substance P [35S] oligonucleotides. Macroscopic and microscopic quantification of enkephalin and substance P gene expression was carried out using computer-assisted image analysis. Tissue was collected from six control cases with no sign of neurological disease and six Huntington's disease cases ranging from grades 0 to 3 as determined by neuropathological evaluation. The clinical and pathological diagnosis of Huntington's disease was confirmed unequivocally by genetic analysis of the CAG repeat length in both copies of IT15, the Huntington's disease gene. A marked reduction in both enkephalin and substance P messenger RNAs was detected in all regions of the caudate nucleus and putamen in Huntington's disease grades 2/3 when compared to controls; in the dorsal caudate few enkephalin or substance P messenger RNA-positive cells were detected. For the early grade (0/1) Huntington's disease cases, a heterogeneous reduction in both enkephalin and substance P messenger RNAs were noted; for enkephalin messenger RNA the striatal autoradiograms displayed a conspicuous patchy appearance. Detailed cellular analysis of the dorsal caudate revealed a striking reduction in the number of enkephalin and substance P messenger RNA-positive cells detected and in the intensity of hybridization signal/cell. These data suggest that both the \"indirect\" GABA/enkephalin and \"direct\" GABA/substance P pathways are perturbed very early in the course of the disease and that these early changes in chemical signalling may possibly underlie the onset of clinical symptoms.",
+ "publisher": "The Journal of biological chemistry",
+ "issn": "1083-351X",
+ "date": "2025-02-25",
+ "abstract": "The repeat expansion in the human genome contributes to neurodegenerative disorders such as spinocerebellar ataxia (SCA) and amyotrophic lateral sclerosis. Transcripts with repeat expansions undergo noncanonical translation called repeat-associated non-AUG (RAN) translation. The NOP56 gene, implicated in SCA36, contains a GGCCTG repeat in its first intron. In tissues of patients with SCA36, poly (Gly-Pro) and poly (Pro-Arg) peptides, likely produced through NOP56 RAN translation in (NOP56-RAN), have been detected. However, the detailed mechanism underlying NOP56-RAN remains unclear. To address this, we used cell-free translation systems to investigate the mechanism of NOP56-RAN and identified the following features. (i) Translation occurs in all reading frames of the sense strand of NOP56 intron 1. (ii) Translation is initiated in a 5' cap-dependent manner from near-cognate start codons upstream of the GGCCUG repeat in each frame. (iii) Longer GGCCUG repeats enhance NOP56-RAN. (iv) A frameshift occurs within the GGCCUG repeat. These findings provide insights into the similarities between NOP56-RAN and other types of RAN translation.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8735227"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40015643"
},
{
- "id": "pmid:8714530",
+ "id": "pmid:36572080",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/8714530",
- "title": "A reproducible assay of polymerase chain reaction to detect trinucleotide repeat expansion of Huntington's disease and senile chorea.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/36572080",
+ "title": "RNA G-quadruplex in live cells lighted-up by a thiazole orange analogue for SCA36 identification.",
"type": "article-journal",
- "doi": "10.1080/01616412.1996.11740370",
+ "doi": "10.1016/j.ijbiomac.2022.12.231",
"authors": [
- ["M", "Watanabe"],
- ["K", "Abe"],
- ["M", "Aoki"],
- ["T", "Kameya"],
- ["Y", "Itoyama"],
- ["M", "Shoji"],
- ["M", "Ikeda"],
- ["T", "Iizuka"],
- ["S", "Hirai"]
+ ["Ranran", "Sun"],
+ ["Xiaomeng", "Guo"],
+ ["Dawei", "Yang"],
+ ["Xinchen", "Cai"],
+ ["Qian", "Li"],
+ ["Li", "Yao"],
+ ["Hongxia", "Sun"],
+ ["Yalin", "Tang"]
],
- "publisher": "Neurological research",
- "issn": "0161-6412",
- "date": "1996-02-01",
- "abstract": "A simple and reproducible method of polymerase chain reaction (PCR) assay was established to detect trinucleotide repeat expansion for Huntington's disease (HD) using a new DNA polymerase and buffer system. The system consists of an extremely heat stable DNA polymerase (Pfu), and a buffer supplemented with ammonium sulfate and dimethyl sulfoxide. Previous methods to amplify expanded alleles for HD have been very complex in PCR conditions, but the reproducibility was sometimes very low because of repetitive sequences around the primer sequences. With the present method, strong bands for the disease alleles were reproducibly visible in a conventional agarose gel stained with ethidium bromide without using isotopes. Three cases with sporadic HD and a case with senile chorea showed expanded alleles for HD with smaller sizes of the expansion than cases with typical HD. These results showed that the present method provides a simple and reproducible way to detect HD allele, and some cases with sporadic HD and senile chorea had expanded HD alleles.",
+ "publisher": "International journal of biological macromolecules",
+ "issn": "1879-0003",
+ "date": "2022-12-23",
+ "abstract": "SCA36 is a neurodegenerative disease mainly caused by the abnormal expansion of the GGGCCT repeat sequence in intron 1 of NOP56. The RNA sequences of this gene are expected to form large amounts of G-quadruplexes in the cytoplasm, which may be a potential intervention and detection target for SCA36. Here, we have developed a small-molecular compound named TCB-1, which shows good selectivity to the G-quadruplex structure, and its fluorescence can be enhanced by hundreds of folds. Interestingly, TCB-1 can avoid lysosome capture, evenly disperse in the cytoplasm, and selectively light up the cytoplasmic RNA G-quadruplexes. This property allows TCB-1 to sensitively detect the increased formation of cytoplasmic RNA G-quadruplexes in SCA36 model cells. This work not only provides new ideas for the design of small-molecule compounds targeting RNA G-quadruplexes in living cells, but also intuitively demonstrates the increased formation of RNA G-quadruplexes caused by NOP56 gene mutation, providing a possible tool for the detection of SCA36.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8714530"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36572080"
},
{
- "id": "pmid:8614526",
+ "id": "pmid:32270466",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/8614526",
- "title": "Trinucleotide repeat length and clinical progression in Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/32270466",
+ "title": "Cerebellar Cognitive Affective Syndrome in Costa da Morte Ataxia (SCA36).",
"type": "article-journal",
- "doi": "10.1212/wnl.46.2.527",
+ "doi": "10.1007/s12311-020-01110-0",
"authors": [
- ["J", "Brandt"],
- ["F W", "Bylsma"],
- ["R", "Gross"],
- ["O C", "Stine"],
- ["N", "Ranen"],
- ["C A", "Ross"]
+ ["R", "Mart\u00ednez-Regueiro"],
+ ["M", "Arias"],
+ ["R", "Cruz"],
+ ["B", "Quint\u00e1ns"],
+ ["T", "Labella-Caballero"],
+ ["M", "Pardo"],
+ ["J", "Pardo"],
+ ["M", "Garc\u00eda-Murias"],
+ ["A", "Carracedo"],
+ ["M-J", "Sobrido"],
+ ["M", "Fern\u00e1ndez-Prieto"]
],
- "publisher": "Neurology",
- "issn": "0028-3878",
- "date": "1996-02-01",
- "abstract": "We examined the relationship between length of the trinucleotide (CAG) repeat at IT-15 and clinical progression of Huntington's disease in 46 mildly to moderately affected patients over a 2-year interval. Patients were divided into those with short mutations (37 to 46 repeats; n = 25) and those with long mutations (> or = 47 repeats; n = 21). Patients with long repeat lengths had earlier age at onset and were younger and less functionally impaired than those with short repeats at the initial visit, but the groups did not differ in severity of neurologic or cognitive impairment. However, the long-repeat group displayed significantly greater decline in both neurologic and cognitive functioning over the 2-year follow-up period. The length of the CAG repeat correlated highly with age at onset (r = -0.72, p < 0.001) and was a strong predictor of decline in both neurologic and cognitive function. The mechanism of gene action, and the means by which longer expansions result in a more malignant disease process, remain to be elucidated.",
+ "publisher": "Cerebellum (London, England)",
+ "issn": "1473-4230",
+ "date": "2020-08-01",
+ "abstract": "SCA36 is an autosomal dominant spinocerebellar ataxia (SCA) affecting many families from Costa da Morte, a northwestern region of Spain. It is caused by an intronic GGCCTG repeat expansion in NOP56. In order to characterize the cognitive and affective manifestations of this cerebellar disease, a group of 30 SCA36 mutation carriers (11 preataxic and 19 ataxic patients) were assessed with a comprehensive battery of standardized tests. Phonological verbal fluency - but not semantic fluency - was already mildly impaired in preataxic subjects. In ataxic patients, both phonological and semantic fluencies were significantly below normal. Depression, while more frequent and prominent in ataxic patients, was also often present in the preataxic stage. This is the first systematic study supporting the presence of a mild cerebellar cognitive and affective syndrome in SCA36. Routine evaluation of cognitive and emotional spheres in SCA36 patients as well as asymptomatic mutation carriers should allow early detection and timely therapeutic intervention.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8614526"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32270466"
},
{
- "id": "pmid:8985734",
+ "id": "pmid:26661328",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/8985734",
- "title": "Relationships of the 2642 deletion polymorphism (delta 2642) in the huntingtin gene with the CAG repeat expansion length and age at onset of the disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26661328",
+ "title": "Genetic and clinical analysis of spinocerebellar ataxia type 36 in Mainland China.",
"type": "article-journal",
- "doi": "",
+ "doi": "10.1111/cge.12706",
"authors": [
- ["G", "Lucotte"],
- ["N", "G\u00e9rard"],
- ["P", "Roubertoux"],
- ["I", "Schmitt"],
- ["O", "Riess"]
+ ["S", "Zeng"],
+ ["J", "Zeng"],
+ ["M", "He"],
+ ["X", "Zeng"],
+ ["Y", "Zhou"],
+ ["Z", "Liu"],
+ ["K", "Xia"],
+ ["Q", "Pan"],
+ ["H", "Jiang"],
+ ["L", "Shen"],
+ ["X", "Yan"],
+ ["B", "Tang"],
+ ["J", "Wang"]
],
- "publisher": "Genetic counseling (Geneva, Switzerland)",
- "issn": "1015-8146",
- "date": "1996-01-01",
- "abstract": "The deletion of 3bp at codon positions 2642-2645 (delta 2642) of the gene mutated in Huntington's disease (HD) was analysed on the normal (N) and HD chromosomes of 79 French families affected with HD, and previously typed for the (CAG)n repeats. delta 2642 Polymorphism has been found over-represented on HD chromosomes, the relative risk of HD with the deletion being at a value of 8.26. In this study, the presence of the deleted allele on HD chromosomes increases the (CAG)n number (47.93 +/- 1.80 versus 43.50 +/- 2.78) and decreases the age of onset (41.34 +/- 2.09 versus 36.90 +/- 2.41) in the patients with versus without delta 2642; so the deletion may add to the severity of the disease. Our studies of delta 2642 on N chromosomes confirm that the deletion event occurs on N chromosomes with a (CAG)n allele length at the upper end of the normal size range.",
+ "publisher": "Clinical genetics",
+ "issn": "1399-0004",
+ "date": "2016-01-20",
+ "abstract": "Spinocerebellar ataxia type 36 (SCA36) is a new SCA subtype recently reported in Japanese and Spanish pedigrees. To assess the frequency and clinical characteristics of SCA36 in patients from Mainland China, we combined the repeat-primed polymerase chain reaction method and Southern blot analysis to detect the GGCCTG hexanucleotide repeats of NOP56 in 364 probands with SCA, 126 probands with hereditary spastic paraplegia and 99 probands with amyotrophic lateral sclerosis (ALS). Systematic and targeted clinical evaluations and investigations were conducted in the SCA36 patients. As a result, eight autosomal dominant spinocerebellar ataxia (ADCA) pedigrees (a total of 13 patients) and one sporadic SCA (S-SCA) patient were identified as SCA36 in the SCA cohort, accounting for approximately 1.60% of the cases in the ADCA group and 0.32% of those in the S-SCA group in Mainland China. The characteristics include late onset and slow progression accompanied by acoustic impairments and 'possible' ALS phenotype in patients from Mainland China.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8985734"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26661328"
},
{
- "id": "pmid:8572659",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/8572659",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:8572659']' timed out after 3 seconds"
+ "id": "pmid:24985895",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/24985895",
+ "title": "Characteristic RNA foci of the abnormal hexanucleotide GGCCUG repeat expansion in spinocerebellar ataxia type 36 (Asidan).",
+ "type": "article-journal",
+ "doi": "10.1111/ene.12491",
+ "authors": [
+ ["W", "Liu"],
+ ["Y", "Ikeda"],
+ ["N", "Hishikawa"],
+ ["T", "Yamashita"],
+ ["K", "Deguchi"],
+ ["K", "Abe"]
+ ],
+ "publisher": "European journal of neurology",
+ "issn": "1468-1331",
+ "date": "2014-07-02",
+ "abstract": "Spinocerebellar ataxia type 36 (SCA36), also called Asidan, is an autosomal-dominant neurodegenerative disorder identified as a hexanucleotide GGCCTG repeat expansion in the first intron 1 of the NOP56 gene. In the present study, for the first time an autopsy sample from an Asidan patient was examined and cytoplasmic inclusions and (GGCCUG)n repeat RNA foci were detected.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24985895"
},
{
- "id": "pmid:8804464",
+ "id": "pmid:22744658",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/8804464",
- "title": "The relevance of VDJ PCR protocols in detecting B-cell clonal expansion in lymphomas and other lymphoproliferative disorders.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22744658",
+ "title": "Clinical features of SCA36: a novel spinocerebellar ataxia with motor neuron involvement (Asidan).",
"type": "article-journal",
- "doi": "10.1177/030089169508100603",
+ "doi": "10.1212/wnl.0b013e318260436f",
"authors": [
- ["V", "De Re"],
- ["S", "De Vita"],
- ["A", "Carbone"],
- ["G", "Ferraccioli"],
- ["A", "Gloghini"],
- ["A", "Marzotto"],
- ["B", "Pivetta"],
- ["R", "Dolcetti"],
- ["M", "Boiocchi"]
+ ["Yoshio", "Ikeda"],
+ ["Yasuyuki", "Ohta"],
+ ["Hatasu", "Kobayashi"],
+ ["Miyuki", "Okamoto"],
+ ["Kazuhiro", "Takamatsu"],
+ ["Taisei", "Ota"],
+ ["Yasuhiro", "Manabe"],
+ ["Koichi", "Okamoto"],
+ ["Akio", "Koizumi"],
+ ["Koji", "Abe"]
],
- "publisher": "Tumori",
- "issn": "0300-8916",
- "date": "1995-01-01",
- "abstract": "The detection of immunoglobulin heavy chain variable (VH)-diversity (DH)-joining (JH) region gene rearrangement by polymerase chain reaction (VDJ PCR) has been recently proposed as a rapid approach to assess B-cell clonality in lymphoproliferative disorders. The aim of the present study was to determine the efficacy of VDJ PCR in a wide spectrum of lymphoproliferative disorders previously characterized by immunohistochemistry and Southern blot (SB).",
+ "publisher": "Neurology",
+ "issn": "1526-632X",
+ "date": "2012-06-27",
+ "abstract": "To characterize the phenotype of spinocerebellar ataxia type 36 (SCA36), a novel dominant disorder (nicknamed \"Asidan\") caused by a hexanucleotide GGCCTG repeat expansion in intron 1 of the NOP56 gene.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8804464"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22744658"
},
{
- "id": "pmid:7576661",
+ "id": "pmid:40635536",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/7576661",
- "title": "CAG expansion affects the expression of mutant Huntingtin in the Huntington's disease brain.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/40635536",
+ "title": "Diverse Clinical Phenotypes of Neuronal Intranuclear Inclusion Disease in South Korea.",
"type": "article-journal",
- "doi": "10.1016/0896-6273(95)90106-x",
+ "doi": "10.3988/jcn.2024.0526",
"authors": [
- ["N", "Aronin"],
- ["K", "Chase"],
- ["C", "Young"],
- ["E", "Sapp"],
- ["C", "Schwarz"],
- ["N", "Matta"],
- ["R", "Kornreich"],
- ["B", "Landwehrmeyer"],
- ["E", "Bird"],
- ["M F", "Beal"]
+ ["Min Young", "Chun"],
+ ["Sang Won", "Seo"],
+ ["Hyemin", "Jang"],
+ ["Duk L", "Na"],
+ ["Seongmi", "Kim"],
+ ["Na Kyung", "Lee"],
+ ["Seung-Yeon", "Lee"],
+ ["Kyung Bok", "Lee"],
+ ["Jinyoung", "Youn"],
+ ["Ja-Hyun", "Jang"],
+ ["Na-Yeon", "Jung"],
+ ["Eun Hye", "Lee"],
+ ["Jee Hyang", "Jeong"],
+ ["Soo Jin", "Yoon"],
+ ["Hyung Chan", "Kim"],
+ ["Joonwon", "Lee"],
+ ["Seongho", "Park"],
+ ["Jinse", "Park"],
+ ["Heejeong", "Jeong"],
+ ["Tae-Won", "Yang"],
+ ["Eungseok", "Oh"],
+ ["Eun-Joo", "Kim"],
+ ["Jiyoung", "Kim"],
+ ["Ji Eun", "Lee"],
+ ["Ji-Yun", "Park"],
+ ["Takeshi", "Mizuguchi"],
+ ["Shinichi", "Kameyama"],
+ ["Naomichi", "Matsumoto"],
+ ["Yeon-Lim", "Suh"],
+ ["Hee Jin", "Kim"]
],
- "publisher": "Neuron",
- "issn": "0896-6273",
- "date": "1995-11-01",
- "abstract": "A trinucleotide repeat (CAG) expansion in the huntingtin gene causes Huntington's disease (HD). In brain tissue from HD heterozygotes with adult onset and more clinically severe juvenile onset, where the largest expansions occur, a mutant protein of equivalent intensity to wild-type huntingtin was detected in cortical synaptosomes, indicating that a mutant species is synthesized and transported with the normal protein to nerve endings. The increased size of mutant huntingtin relative to the wild type was highly correlated with CAG repeat expansion, thereby linking an altered electrophoretic mobility of the mutant protein to its abnormal function. Mutant huntingtin appeared in gray and white matter with no difference in expression in affected regions. The mutant protein was broader than the wild type and in 6 of 11 juvenile cases resolved as a complex of bands, consistent with evidence at the DNA level for somatic mosaicism. Thus, HD pathogenesis results from a gain of function by an aberrant protein that is widely expressed in brain and is harmful only to some neurons.",
+ "publisher": "Journal of clinical neurology (Seoul, Korea)",
+ "issn": "1738-6586",
+ "date": "2025-07-01",
+ "abstract": "Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disease characterized by a wide range of clinical manifestations. GGC-repeat expansion in",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7576661"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40635536"
},
{
- "id": "pmid:7668287",
+ "id": "pmid:40517194",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/7668287",
- "title": "Anticipation and instability of IT-15 (CAG)n repeats in parent-offspring pairs with Huntington disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/40517194",
+ "title": "Retinal degeneration as an initial manifestation in a patient with neuronal intranuclear inclusion disease.",
"type": "article-journal",
- "doi": "",
+ "doi": "10.1007/s10633-025-10035-0",
"authors": [
- ["N G", "Ranen"],
- ["O C", "Stine"],
- ["M H", "Abbott"],
- ["M", "Sherr"],
- ["A M", "Codori"],
- ["M L", "Franz"],
- ["N I", "Chao"],
- ["A S", "Chung"],
- ["N", "Pleasant"],
- ["C", "Callahan"]
+ ["Shijing", "Wu"],
+ ["Ailing", "Sui"],
+ ["Qianyi", "Zhan"],
+ ["Qiuli", "Fu"],
+ ["Li", "Zhang"]
],
- "publisher": "American journal of human genetics",
- "issn": "0002-9297",
- "date": "1995-09-01",
- "abstract": "Huntington disease (HD) is an autosomal dominant degenerative disorder caused by an expanded and unstable trinucleotide repeat (CAG)n in a gene (IT-15) on chromosome 4. HD exhibits genetic anticipation--earlier onset in successive generations within a pedigree. From a population-based clinical sample, we ascertained parent-offspring pairs with expanded alleles, to examine the intergenerational behavior of the trinucleotide repeat and its relationship to anticipation. We find that the change in repeat length with paternal transmission is significantly correlated with the change in age at onset between the father and offspring. When expanded triplet repeats of affected parents are separated by median repeat length, we find that the longer paternal and maternal repeats are both more unstable on transmission. However, unlike in paternal transmission, in which longer expanded repeats display greater net expansion than do shorter expanded repeats, in maternal transmission there is no mean change in repeat length for either longer or shorter expanded repeats. We also confirmed the inverse relationship between repeat length and age at onset, the higher frequency of juvenile-onset cases arising from paternal transmission, anticipation as a phenomenon of paternal transmission, and greater expansion of the trinucleotide repeat with paternal transmission. Stepwise multiple regression indicates that, in addition to repeat length of offspring, age at onset of affected parent and sex of affected parent contribute significantly to the variance in age at onset of the offspring. Thus, in addition to triplet repeat length, other factors, which could act as environmental factors, genetic factors, or both, contribute to age at onset. Our data establish that further expansion of paternal repeats within the affected range provides a biological basis of anticipation in HD.",
+ "publisher": "Documenta ophthalmologica. Advances in ophthalmology",
+ "issn": "1573-2622",
+ "date": "2025-06-14",
+ "abstract": "Neuronal intranuclear inclusion disease (NIID) is a rare autosomal dominant, progressive neurodegenerative disorder characterized by a broad spectrum of clinical conditions, including pyramidal and extrapyramidal symptoms, cerebellar ataxia, cognitive decline and dementia, peripheral neuropathy, and autonomic dysfunction.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7668287"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40517194"
},
{
- "id": "pmid:7668260",
+ "id": "pmid:40515658",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/7668260",
- "title": "Sex-dependent mechanisms for expansions and contractions of the CAG repeat on affected Huntington disease chromosomes.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/40515658",
+ "title": "Psychiatric-onset neuronal intranuclear inclusion disease in a psychiatry-based dementia-enriched cohort in Japan.",
"type": "article-journal",
- "doi": "",
+ "doi": "10.1111/pcn.13854",
"authors": [
- ["B", "Kremer"],
- ["E", "Almqvist"],
- ["J", "Theilmann"],
- ["N", "Spence"],
- ["H", "Telenius"],
- ["Y P", "Goldberg"],
- ["M R", "Hayden"]
+ ["Tesshin", "Miyamoto"],
+ ["Kohji", "Mori"],
+ ["Shoshin", "Akamine"],
+ ["Shizuko", "Kondo"],
+ ["Shiho", "Gotoh"],
+ ["Ryota", "Uozumi"],
+ ["Sumiyo", "Umeda"],
+ ["Hanako", "Koguchi-Yoshioka"],
+ ["Satoshi", "Nojima"],
+ ["Daiki", "Taomoto"],
+ ["Yuto", "Satake"],
+ ["Takashi", "Suehiro"],
+ ["Hideki", "Kanemoto"],
+ ["Kenji", "Yoshiyama"],
+ ["Takashi", "Morihara"],
+ ["Manabu", "Ikeda"]
],
- "publisher": "American journal of human genetics",
- "issn": "0002-9297",
- "date": "1995-08-01",
- "abstract": "A total of 254 affected parent-child pairs with Huntington disease (HD) and 440 parent-child pairs with CAG size in the normal range were assessed to determine the nature and frequency of intergenerational CAG changes in the HD gene. Intergenerational CAG changes are extremely rare (3/440 [0.68%]) on normal chromosomes. In contrast, on HD chromosomes, changes in CAG size occur in approximately 70% of meioses on HD chromosomes, with expansions accounting for 73% of these changes. These intergenerational CAG changes make a significant but minor contribution to changes in age at onset (r2 = .19). The size of the CAG repeat influenced larger intergenerational expansions (> 7 CAG repeats), but the likelihood of smaller expansions or contractions was not influenced by CAG size. Large expansions (> 7 CAG repeats) occur almost exclusively through paternal transmission (0.96%; P < 10(-7)), while offspring of affected mothers are more likely to show no change (P = .01) or contractions in CAG size (P = .002). This study demonstrates that sex of the transmitting parent is the major determinant for CAG intergenerational changes in the HD gene. Similar paternal sex effects are seen in the evolution of new mutations for HD from intermediate alleles and for large expansions on affected chromosomes. Affected mothers almost never transmit a significantly expanded CAG repeat, despite the fact that many have similar large-sized alleles, compared with affected fathers. The sex-dependent effects of major expansion and contractions of the CAG repeat in the HD gene implicate different effects of gametogenesis, in males versus females, on intergenerational CAG repeat stability.",
+ "publisher": "Psychiatry and clinical neurosciences",
+ "issn": "1440-1819",
+ "date": "2025-06-14",
+ "abstract": "A GGC repeat expansion in the 5' untranslated region of NOTCH2NLC is a genetic cause of Neuronal Intranuclear Inclusion Disease (NIID) that exhibits cognitive, motor, and autonomic dysfunction. Our objective is to determine whether there are undiagnosed NIID cases in a psychiatry-based dementia-enriched cohort and to identify their clinical characteristics.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7668260"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40515658"
},
{
- "id": "pmid:7639626",
+ "id": "pmid:39529621",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/7639626",
- "title": "Correlations between triplet repeat expansion and clinical features in Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/39529621",
+ "title": "Neuronal Intranuclear Inclusion Disease Presenting with Acute-Onset Dementia and Cortical Edema: A Case Report.",
"type": "article-journal",
- "doi": "10.1001/archneur.1995.00540320021009",
+ "doi": "10.3389/fneur.2024.1464991",
"authors": [
- ["S", "Claes"],
- ["K", "Van Zand"],
- ["E", "Legius"],
- ["R", "Dom"],
- ["M", "Malfroid"],
- ["F", "Baro"],
- ["J", "Godderis"],
- ["J J", "Cassiman"]
+ ["Xiao", "Feng"],
+ ["Yue", "Li"],
+ ["Qin", "Zhao"],
+ ["Shabei", "Xu"]
],
- "publisher": "Archives of neurology",
- "issn": "0003-9942",
- "date": "1995-08-01",
- "abstract": "To investigate possible correlations between the length of the (CAG)n trinucleotide repeat in Hungtington's disease gene IT15 and clinical features (age at onset, symptoms at onset, and mode of progression) in Huntington's disease.",
+ "publisher": "Frontiers in neurology",
+ "issn": "1664-2295",
+ "date": "2024-10-28",
+ "abstract": "Neuronal Intranuclear Inclusion Disease (NIID) is a neurodegenerative disorder characterized by the formation of eosinophilic inclusions in the neurons, visceral and skin cells. The cause is associated with the GGC nucleotide repeat expansion in the NOTCH2NLC gene. The imaging hallmark of NIID is hyperintensities on diffusion-weighted imaging (DWI) at the corticomedullary junction. Clinical manifestations of NIID are highly heterogeneous. Here, we report a case of NIID presenting with acute-onset dementia and cortical edema.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7639626"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39529621"
},
{
- "id": "pmid:7675777",
+ "id": "pmid:39505310",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/7675777",
- "title": "Epstein-Bar virus and progression of non-Hodgkin's lymphoma to Ki-1-positive, anaplastic large cell phenotype.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/39505310",
+ "title": "CGG Repeat Expansion in",
"type": "article-journal",
- "doi": "",
+ "doi": "10.3988/jcn.2023.0486",
"authors": [
- ["J A", "DiGiuseppe"],
- ["T C", "Wu"],
- ["B A", "Zehnbauer"],
- ["P R", "McDowell"],
- ["J M", "Barletta"],
- ["R F", "Ambinder"],
- ["R B", "Mann"]
+ ["Jing", "Ma"],
+ ["Huiqiu", "Zhang"],
+ ["Bing", "Meng"],
+ ["Jiangbo", "Qin"],
+ ["Hongye", "Liu"],
+ ["Xiaomin", "Pang"],
+ ["Rongjuan", "Zhao"],
+ ["Juan", "Wang"],
+ ["Xueli", "Chang"],
+ ["Junhong", "Guo"],
+ ["Wei", "Zhang"]
],
- "publisher": "Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc",
- "issn": "0893-3952",
- "date": "1995-06-01",
- "abstract": "Epstein-Barr virus (EBV) has been implicated in the pathogenesis of a variety of lymphoproliferative disorders (LPDs) including endemic Burkitt's lymphoma, Hodgkin's disease (HD), HIV-associated non-Hodgkin's lymphomas (NHLs), and LPDs arising in immunosuppressed transplant patients. More recently, EBV has been associated with Ki-1-positive anaplastic large cell lymphoma (ALCL), a recently described NHL that shares with HD expression of the CD30 antigen Ki-1. Because EBV has been shown to induce Ki-1 expression in vitro, and ALCL has been diagnosed in patients with prior or concurrent HD or NHL, it has been proposed that EBV may mediate progression of a \"primary\" lymphoma to a \"secondary\" ALCL. We report a case in which an AIDS-associated, Ki-1-negative, large-cell immunoblastic lymphoma progressed to a Ki-1 positive ALCL. Analysis of the immunoglobulin heavy chain locus revealed a clonal relationship between these morphologically and immunophenotypically distinct tumors. Although EBV was absent from the original large-cell immunoblastic lymphoma as assessed by in situ hybridization for EBV-encoded small RNA1 (EBER1), polymerase chain reaction for EBNA-1, immunocytochemistry for latent membrane protein 1, and Southern blot hybridization for EBV terminal repeat sequences, all for techniques confirmed the presence of EBV in the secondary ALCL. Moreover, analysis of EBV terminal repeat sequences indicated that the ALCL resulted from expansion of a single EBV-infected clone. These data suggest that EBV may mediate progression of NHL to Ki-1-positive ALCL, and that in some instances, EBV may be involved in the later stages of clonal progression of NHL.",
+ "publisher": "Journal of clinical neurology (Seoul, Korea)",
+ "issn": "1738-6586",
+ "date": "2024-11-01",
+ "abstract": "CGG repeat expansion in the 5' untranslated region (5'UTR) of the Notch 2 N-terminal-like C gene (",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7675777"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39505310"
},
{
- "id": "pmid:7898693",
+ "id": "pmid:38779172",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/7898693",
- "title": "Hereditary late-onset chorea without significant dementia: genetic evidence for substantial phenotypic variation in Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38779172",
+ "title": "Prevalence and Characterization of",
"type": "article-journal",
- "doi": "10.1212/wnl.45.3.443",
+ "doi": "10.1212/nxg.0000000000200147",
"authors": [
- ["J W", "Britton"],
- ["R J", "Uitti"],
- ["J E", "Ahlskog"],
- ["R G", "Robinson"],
- ["B", "Kremer"],
- ["M R", "Hayden"]
+ ["Seungbok", "Lee"],
+ ["Jihoon G", "Yoon"],
+ ["Juhyeon", "Hong"],
+ ["Taekeun", "Kim"],
+ ["Narae", "Kim"],
+ ["Jana", "Vandrovcova"],
+ ["Wai Yan", "Yau"],
+ ["Jaeso", "Cho"],
+ ["Sheehyun", "Kim"],
+ ["Man Jin", "Kim"],
+ ["Soo Yeon", "Kim"],
+ ["Soon-Tae", "Lee"],
+ ["Kon", "Chu"],
+ ["Sang Kun", "Lee"],
+ ["Han-Joon", "Kim"],
+ ["Jungmin", "Choi"],
+ ["Jangsup", "Moon"],
+ ["Jong-Hee", "Chae"]
],
- "publisher": "Neurology",
- "issn": "0028-3878",
- "date": "1995-03-01",
- "abstract": "We examined five individuals and obtained information concerning six other members from two unrelated families, nearly all of whom developed chorea after age 50 (one patient developed chorea at age 40). The severity of chorea progressed in all patients and became disabling in some individuals approximately 15 years after onset. Cognitive impairment was absent or minimal. All five examined patients were cognitively normal, even 10 to 30 years following the onset of chorea. Formal neuropsychometric testing demonstrated mild cognitive impairment in two individuals. Nevertheless, all patients were able to maintain employment or carry on with their usual household tasks until chorea was severe. One individual first became demented 30 years after the onset of chorea. Neuroimaging (with CT or MRI) in four patients failed to demonstrate significant caudate or putaminal atrophy 8 to 15 years following the onset of chorea. Three other family members (who were not available for examination) were said to have suffered chorea (without any mental decline) beginning after age 50, with subsequent survival of 20 years (in one) and 30 years (in two). Given this constellation of history and findings, three experienced neurologists and two medical geneticists concluded that these patients had a familial chorea syndrome distinct from Huntington's disease (HD). However, genetic analysis of the trinucleotide (CAG) repeat length associated with HD (in 4p16.3) determined repeat lengths of 44 and 46 in four patients tested (within the HD range). We conclude that these patients have HD and that such families represent further convincing examples of significant phenotypic variation for HD.",
+ "publisher": "Neurology. Genetics",
+ "issn": "2376-7839",
+ "date": "2024-05-20",
+ "abstract": "GGC repeat expansions in the",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7898693"
-},
-{
- "id": "pmid:7868117",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/7868117",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:7868117']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38779172"
},
{
- "id": "pmid:7881406",
+ "id": "pmid:38579412",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/7881406",
- "title": "DNA haplotype analysis of Huntington disease reveals clues to the origins and mechanisms of CAG expansion and reasons for geographic variations of prevalence.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38579412",
+ "title": "Neuronal intranuclear inclusion disease in New Zealand: A novel discovery.",
"type": "article-journal",
- "doi": "10.1093/hmg/3.12.2103",
+ "doi": "10.1016/j.jns.2024.122987",
"authors": [
- ["F", "Squitieri"],
- ["S E", "Andrew"],
- ["Y P", "Goldberg"],
- ["B", "Kremer"],
- ["N", "Spence"],
- ["J", "Zeisler"],
- ["K", "Nichol"],
- ["J", "Theilmann"],
- ["J", "Greenberg"],
- ["J", "Goto"]
+ ["Tony", "Zhang"],
+ ["Andrew", "Chancellor"],
+ ["Bernard", "Liem"],
+ ["Clinton", "Turner"],
+ ["David", "Hutchinson"],
+ ["Edward", "Wong"],
+ ["Emma", "Glamuzina"],
+ ["Jae Beom", "Hong"],
+ ["James", "Cleland"],
+ ["Nicholas", "Child"],
+ ["Richard H", "Roxburgh"],
+ ["Shilpan", "Patel"],
+ ["Yi-Chung", "Lee"],
+ ["Yi-Chu", "Liao"],
+ ["Neil E", "Anderson"]
],
- "publisher": "Human molecular genetics",
- "issn": "0964-6906",
- "date": "1994-12-01",
- "abstract": "This study of allelic association using three intra- and two extragenic markers within 150 kb of the Huntington disease (HD) mutation has provided evidence for linkage disequilibrium for four of five markers. Haplotype analysis of 67 HD families using markers in strong linkage disequilibrium with HD identified two haplotypes underlying 77.6% of HD chromosomes. Normal chromosomes with these two haplotypes had a mean number of CAG repeats significantly larger than and an altered distribution of CAG repeats compared with other normal chromosomes. Furthermore, haplotype analysis of five new mutation families reveals that HD has arisen on these same two chromosomal haplotypes. These findings suggest that HD arises more frequently on chromosomes with specific DNA haplotypes and higher CAG repeat lengths. We then studied CAG and CCG repeat lengths in the HD gene on 896 control chromosomes from different ancestries to determine whether the markedly reduced frequency of HD in Finland, Japan, China and African Blacks is associated with an altered frequency of DNA haplotypes and subsequently lower CAG lengths on control chromosomes compared to populations of Western European descent. The results show a highly significant inverse relationship between CAG and CCG repeat lengths. In populations with lowered prevalence rates of HD, CAG repeat lengths are smaller and the distribution of CCG alleles is markedly different from Western European populations. These findings suggest that, in addition to European emigration, new mutations make a contribution to geographical variation of prevalence rates and is consistent with a multistep model of HD developing from normal chromosomes with higher CAG repeat lengths.",
+ "publisher": "Journal of the neurological sciences",
+ "issn": "1878-5883",
+ "date": "2024-04-03",
+ "abstract": "Neuronal intranuclear inclusion disease, caused by a GGC repeat expansion in the 5'-untranslated region of NOTCH2NLC, is a rare neurodegenerative condition with highly variable clinical manifestations. In recent years, the number of reported cases have increased dramatically in East Asia. We report the first four genetically confirmed cases of neuronal intranuclear inclusion disease in New Zealand, all having Polynesian ancestry (three New Zealand M\u0101ori and one Cook Island M\u0101ori). Phenotypically, they resemble cases reported from recent large East Asian cohorts.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7881406"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38579412"
},
{
- "id": "pmid:7969980",
+ "id": "pmid:38477063",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/7969980",
- "title": "Normal CAG repeat length in the Huntington's disease gene in senile chorea.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38477063",
+ "title": "The predominance of \"astrocytic\" intranuclear inclusions in neuronal intranuclear inclusion disease manifesting encephalopathy-like symptoms: A case series with brain biopsy.",
"type": "article-journal",
- "doi": "10.1212/wnl.44.11.2183",
+ "doi": "10.1111/neup.12971",
"authors": [
- ["H", "Shinotoh"],
- ["D B", "Calne"],
- ["B", "Snow"],
- ["M", "Hayward"],
- ["B", "Kremer"],
- ["J", "Theilmann"],
- ["M R", "Hayden"]
+ ["Keisuke", "Ishizawa"],
+ ["Takashi", "Komori"],
+ ["Taku", "Homma"],
+ ["Jun", "Sone"],
+ ["Yasuhiro", "Nakata"],
+ ["Yoshihiko", "Nakazato"],
+ ["Kazushi", "Takahashi"],
+ ["Toshimasa", "Yamamoto"],
+ ["Atsushi", "Sasaki"]
],
- "publisher": "Neurology",
- "issn": "0028-3878",
- "date": "1994-11-01",
- "abstract": "There is a widely held belief that most patients presenting with senile chorea have late-onset Huntington's disease (HD) with an unknown family history. We measured CAG trinucleotide repeat expansion in the HD gene in four patients with a clinical presentation of senile chorea and found that CAG repetition lengths were normal. These findings support senile chorea as being a distinct clinical entity that is nosologically separate from late-onset HD.",
+ "publisher": "Neuropathology : official journal of the Japanese Society of Neuropathology",
+ "issn": "1440-1789",
+ "date": "2024-03-13",
+ "abstract": "Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder represented by eosinophilic intranuclear inclusions (EIIs) and GGC/CGG repeat expansion in the NOTCH2NLC gene. We report here two adult cases of NIID, genetically confirmed, with manifestation of encephalopathy-like symptoms and address the histopathologic findings obtained by brain biopsies, with a focus on \"astrocytic\" intranuclear inclusions (AIIs). Case 1 presented with paroxysmal restlessness, vertigo, or fever and was later involved in severe dementia and tetraparesis. Case 2 presented with forgetfulness and then with paroxysmal fever and headache. In both cases, delimited areas with gadolinium enhancement on magnetic resonance imaging and corresponding hyperperfusion were detected, leading to brain biopsies of the cortex. On histology, Case 1 showed an abnormal lamination, where the thickness of layers was different from usual. Both neurons and astrocytes showed some dysmorphologic features. Notably, astrocytes rather than neurons harbored EIIs. Case 2 showed a cortex, where neurons tended to be arrayed in a columnar fashion. Astrocytes showed some dysmorphologic features. Notably, much more astrocytes than neurons harbored EIIs. By a double-labeling immunofluorescence study for p62/NeuN and p62/glial fibrillary acidic protein, the predominance of AIIs was confirmed in both cases. Considering the physiological functions of astrocytes for the development and maintenance of the cortex, the encephalopathy-like symptoms, dynamic change of cerebral blood flow, and cortical dysmorphology can reasonably be explained by the dysfunction of EII-bearing astrocytes rather than EII-bearing neurons. This study suggests the presence of a subtype of NIID where AIIs rather than \"neuronal\" intranuclear inclusions are likely a key player in the pathogenesis of NIID, particularly in cases with encephalopathy-like symptoms. The importance of AIIs (\"gliopathy\") should be more appreciated in future studies of NIID.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7969980"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38477063"
},
{
- "id": "pmid:7959696",
+ "id": "pmid:37975799",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/7959696",
- "title": "Trinucleotide (CAG) repeat expansion in chromosomes of Spanish patients with Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/37975799",
+ "title": "GGC expansions in NOTCH2NLC contribute to Parkinson disease and dopaminergic neuron degeneration.",
"type": "article-journal",
- "doi": "10.1007/bf00211028",
+ "doi": "10.1111/ene.16145",
"authors": [
- ["J", "Benitez"],
- ["E", "Fernandez"],
- ["P", "Garcia Ruiz"],
- ["M", "Robledo"],
- ["C", "Ramos"],
- ["J", "Y\u00e9benes"]
+ ["Qiong", "Liu"],
+ ["Juan", "Chen"],
+ ["Jin", "Xue"],
+ ["Xun", "Zhou"],
+ ["Yun", "Tian"],
+ ["Qiao", "Xiao"],
+ ["Wen", "Huang"],
+ ["Yongcheng", "Pan"],
+ ["Xiaoxia", "Zhou"],
+ ["Jian", "Li"],
+ ["Yuwen", "Zhao"],
+ ["Hongxu", "Pan"],
+ ["Yige", "Wang"],
+ ["Runcheng", "He"],
+ ["Yaqin", "Xiang"],
+ ["Tian", "Tu"],
+ ["Qian", "Xu"],
+ ["Qiying", "Sun"],
+ ["Jieqiong", "Tan"],
+ ["Xinxiang", "Yan"],
+ ["Jinchen", "Li"],
+ ["Jifeng", "Guo"],
+ ["Lu", "Shen"],
+ ["Ranhui", "Duan"],
+ ["Beisha", "Tang"],
+ ["Zhenhua", "Liu"]
],
- "publisher": "Human genetics",
- "issn": "0340-6717",
- "date": "1994-11-01",
- "abstract": "Huntington's disease (HD) is a neurodegenerative and hereditary disease characterized by progressive movement disorders and mental and behavioral abnormalities. The HD gene is an expanding and unstable trinucleotide repeat (CAG repeat sequences). We studied 77 individuals from 38 families with HD in an attempt to obtain information for genetic counselling and differential diagnosis. Our results indicate that individuals with more than 40 repeats will be affected by the disease, whereas those with fewer than 30 will be healthy. There can be some overlap between 30 and 40 repeats, and one should be careful when interpreting these results.",
+ "publisher": "European journal of neurology",
+ "issn": "1468-1331",
+ "date": "2023-11-17",
+ "abstract": "The role of GGC repeat expansions within NOTCH2NLC in Parkinson's disease (PD) and the substantia nigra (SN) dopaminergic neuron remains unclear. Here, we profile the NOTCH2NLC GGC repeat expansions in a large cohort of patients with PD. We also investigate the role of GGC repeat expansions within NOTCH2NLC in the dopaminergic neurodegeneration of SN.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7959696"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37975799"
},
{
- "id": "pmid:7815437",
+ "id": "pmid:37644522",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/7815437",
- "title": "Study of the Huntington's disease (HD) gene CAG repeats in schizophrenic patients shows overlap of the normal and HD affected ranges but absence of correlation with schizophrenia.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/37644522",
+ "title": "Expression of expanded GGC repeats within NOTCH2NLC causes cardiac dysfunction in mouse models.",
"type": "article-journal",
- "doi": "10.1136/jmg.31.9.690",
+ "doi": "10.1186/s13578-023-01111-6",
"authors": [
- ["D C", "Rubinsztein"],
- ["J", "Leggo"],
- ["S", "Goodburn"],
- ["T J", "Crow"],
- ["R", "Lofthouse"],
- ["L E", "DeLisi"],
- ["D E", "Barton"],
- ["M A", "Ferguson-Smith"]
+ ["Yongcheng", "Pan"],
+ ["Ying", "Jiang"],
+ ["Juan", "Wan"],
+ ["Zhengmao", "Hu"],
+ ["Hong", "Jiang"],
+ ["Lu", "Shen"],
+ ["Beisha", "Tang"],
+ ["Yun", "Tian"],
+ ["Qiong", "Liu"]
],
- "publisher": "Journal of medical genetics",
- "issn": "0022-2593",
- "date": "1994-09-01",
- "abstract": "The CAG repeats in the Huntington's disease gene were investigated in chromosomes from 71 unrelated schizophrenic persons and 18 patients with schizoaffective disorder in order to determine if any of these patients had abnormal expansions. All of the probands had repeat sizes in the normal range (< 35 repeats) and there was no significant difference between the allele distributions of these patients and the normal controls. The families of two patients with 32 repeats and one patient with 34 repeats were investigated further and showed no uniform segregation of the disease with the large repeat alleles. The proband with 34 repeats inherited a chromosome that originally had 36 repeats in her father. The presence of 36 CAG repeats in members of her family and in HD patients suggests that there is an overlap between the normal and Huntington's disease CAG repeat size ranges. The more recently described CCG polymorphism in this gene was also examined in the schizophrenic and schizoaffective persons. All patients had alleles in the normal range.",
+ "publisher": "Cell & bioscience",
+ "issn": "2045-3701",
+ "date": "2023-08-29",
+ "abstract": "Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder characterized by widespread intranuclear inclusions in the nervous system as well as multiple visceral organs. In 2019, expanded GGC repeats within the 5' untranslated region of the NOTCH2NLC gene was identified as the causative factor. NIID is a heterogeneous disorder with variable clinical manifestations including cognitive impairment, cerebellar ataxia, parkinsonism, paroxysmal symptoms, autonomic dysfunction, and muscle weakness. Although NIID primarily affects the central and peripheral nervous systems, growing evidence suggests potential cardiac abnormalities in NIID. However, the link between expanded GGC repeats within NOTCH2NLC and cardiac dysfunction remains uncertain.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7815437"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37644522"
},
{
- "id": "pmid:8208412",
+ "id": "pmid:37184590",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/8208412",
- "title": "CAG repeat size and clinical presentation in Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/37184590",
+ "title": "A comprehensive study of clinicopathological and genetic features of neuronal intranuclear inclusion disease.",
"type": "article-journal",
- "doi": "10.1212/wnl.44.6.1137",
+ "doi": "10.1007/s10072-023-06845-2",
"authors": [
- ["T", "Ashizawa"],
- ["L J", "Wong"],
- ["C S", "Richards"],
- ["C T", "Caskey"],
- ["J", "Jankovic"]
+ ["Minglei", "Liu"],
+ ["Yuan", "Gao"],
+ ["Yanpeng", "Yuan"],
+ ["Xiaojing", "Liu"],
+ ["Yangyang", "Wang"],
+ ["Lanjun", "Li"],
+ ["Xiaoyun", "Zhang"],
+ ["Chenyang", "Jiang"],
+ ["Qingzhi", "Wang"],
+ ["Yanlin", "Wang"],
+ ["Changhe", "Shi"],
+ ["Yuming", "Xu"],
+ ["Jing", "Yang"]
],
- "publisher": "Neurology",
- "issn": "0028-3878",
- "date": "1994-06-01",
- "abstract": "The specific mutation in Huntington's disease (HD) is an expansion of the unstable CAG trinucleotide repeat in the IT15 gene in chromosome 4p. We examined the relationship between the CAG repeat size and clinical presentation in 36 patients with suspected diagnosis of HD. Twelve patients had no relatives with documented HD, and five of them failed to show the expanded (>37) CAG repeats. The remaining 31 patients, including seven patients with atypical clinical features for HD (three without and four with family history of documented HD), were heterozygotes for the CAG repeat expansion. There were large CAG repeats (50 copies) in paternally transmitted HD cases with early onset (age 30 or earlier). The rate of disease progression was faster in paternally transmitted cases regardless of the CAG repeat length or age of onset. We conclude that (1) patients lacking the family history of HD frequently show no expansion of the CAG repeats, and (2) the sex of the affected parent influences both the CAG repeat size and the phenotypic expression of the HD gene in the offspring.",
+ "publisher": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology",
+ "issn": "1590-3478",
+ "date": "2023-05-15",
+ "abstract": "The discovery of skin intranuclear inclusions and GGC repeat expansion of NOTCH2NLC has greatly promoted the diagnosis of neuronal intranuclear inclusion disease (NIID). With highly heterogeneous clinical manifestations, NIID patients tend to be underdiagnosed at early stages.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8208412"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37184590"
},
{
- "id": "pmid:8178825",
+ "id": "pmid:37131242",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/8178825",
- "title": "Huntington disease without CAG expansion: phenocopies or errors in assignment?",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/37131242",
+ "title": "NOTCH2NLC GGC repeat expansion causes retinal pathology with intranuclear inclusions throughout the retina and causes visual impairment.",
"type": "article-journal",
- "doi": "",
+ "doi": "10.1186/s40478-023-01564-3",
"authors": [
- ["S E", "Andrew"],
- ["Y P", "Goldberg"],
- ["B", "Kremer"],
- ["F", "Squitieri"],
- ["J", "Theilmann"],
- ["J", "Zeisler"],
- ["H", "Telenius"],
- ["S", "Adam"],
- ["E", "Almquist"],
- ["M", "Anvret"]
+ ["Jun", "Sone"],
+ ["Shinji", "Ueno"],
+ ["Akio", "Akagi"],
+ ["Hiroaki", "Miyahara"],
+ ["Chisato", "Tamai"],
+ ["Yuichi", "Riku"],
+ ["Hiroyuki", "Yabata"],
+ ["Ryuichi", "Koizumi"],
+ ["Tomohiro", "Hattori"],
+ ["Hiroshi", "Hirose"],
+ ["Yoshito", "Koyanagi"],
+ ["Rei", "Kobayashi"],
+ ["Hisashi", "Okada"],
+ ["Yoshiyuki", "Kishimoto"],
+ ["Yoshio", "Hashizume"],
+ ["Gen", "Sobue"],
+ ["Mari", "Yoshida"],
+ ["Yasushi", "Iwasaki"]
],
- "publisher": "American journal of human genetics",
- "issn": "0002-9297",
- "date": "1994-05-01",
- "abstract": "Huntington disease (HD) has been shown to be associated with an expanded CAG repeat within a novel gene on 4p16.3 (IT15). A total of 30 of 1,022 affected persons (2.9% of our cohort) did not have an expanded CAG in the disease range. The reasons for not observing expansion in affected individuals are important for determining the sensitivity of using repeat length both for diagnosis of affected patients and for predictive testing programs and may have biological relevance for the understanding of the molecular mechanism underlying HD. Here we show that the majority (18) of the individuals with normal sized alleles represent misdiagnosis, sample mix-up, or clerical error. The remaining 12 patients represent possible phenocopies for HD. In at least four cases, family studies of these phenocopies excluded 4p16.3 as the region responsible for the phenotype. Mutations in the HD gene that are other than CAG expansion have not been excluded for the remaining eight cases; however, in as many as seven of these persons, retrospective review of these patients' clinical features identified characteristics not typical for HD. This study shows that on rare occasions mutations in other, as-yet-undefined genes can present with a clinical phenotype very similar to that of HD.",
+ "publisher": "Acta neuropathologica communications",
+ "issn": "2051-5960",
+ "date": "2023-05-02",
+ "abstract": "The retinal pathology of genetically confirmed neuronal intranuclear inclusion disease (NIID) is yet unknown. We report the ocular findings in four NIID patients with NOTCH2NLC GGC repeat expansion to investigate the pathology of retinopathy. All four NIID patients were diagnosed by skin biopsy and NOTCH2NLC GGC repeat analysis. Ocular findings in patients with NIID were studied using fundus photographs, optical coherence tomographic images (OCT), and full-field electroretinograms (ERGs). The histopathology of the retina was studied on autopsy samples from two cases with immunohistochemistry. All patients had an expansion of the GGC repeat (87-134 repeats) in the NOTCH2NLC. Two patients were legally blind and had been diagnosed with retinitis pigmentosa prior to the diagnosis of NIID and assessed with whole exome sequencing to rule out comorbidity with other retinal diseases. Fundus photographs around the posterior pole showed chorioretinal atrophy in the peripapillary regions. OCT showed thinning of the retina. ERGs showed various abnormalities in cases. The histopathology of autopsy samples showed diffusely scattered intranuclear inclusions throughout the retina from the retinal pigment epithelium to the ganglion cell layer, and optic nerve glial cells. And severe gliosis was observed in retina and optic nerve. The NOTCH2NLC GGC repeat expansion causes numerous intranuclear inclusions in the retina and optic nerve cells and gliosis. Visual dysfunction could be the first sign of NIID. We should consider NIID as one of the causes of retinal dystrophy and investigate the GGC repeat expansion in NOTCH2NLC.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8178825"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37131242"
},
{
- "id": "pmid:8162053",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/8162053",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:8162053']' timed out after 3 seconds"
+ "id": "pmid:37001413",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/37001413",
+ "title": "Clinical, radiological, and molecular analyses of neuronal intranuclear inclusion disease with polyglycine inclusions.",
+ "type": "article-journal",
+ "doi": "10.1016/j.jns.2023.120618",
+ "authors": [
+ ["Minori", "Furuta"],
+ ["Masayuki", "Sato"],
+ ["Hiroo", "Kasahara"],
+ ["Setsuki", "Tsukagoshi"],
+ ["Kimitoshi", "Hirayanagi"],
+ ["Yukio", "Fujita"],
+ ["Eriko", "Takai"],
+ ["Yuko", "Aihara"],
+ ["Koichi", "Okamoto"],
+ ["Yoshio", "Ikeda"]
+ ],
+ "publisher": "Journal of the neurological sciences",
+ "issn": "1878-5883",
+ "date": "2023-03-22",
+ "abstract": "Neuronal intranuclear inclusion disease (NIID) is a clinically complex neurological disorder that appears sporadically or autosomally. Expansions of intronic GGC trinucleotide repeats in the NOTCH2 N-terminal-like C (NOTCH2NLC) gene cause NIID. In this study, to clarify the clinical characteristics useful for the differential diagnosis of NIID, clinical data of neurological examination, neuroimaging, and nerve conduction studies of six NIID patients diagnosed by pathological or genetic investigations were analyzed. Clinically useful characteristics for diagnosing NIID include general hyporeflexia, episodic disturbance of consciousness, sensory disturbance, miosis, and dementia. Furthermore, neuroimaging findings, such as leukoencephalopathy in T2-weighted magnetic resonance imaging and a linear high intensity of subcortical U-fibers in diffusion-weighted imaging (DWI), as well as decreased motor nerve conduction velocity, are especially important biomarkers for NIID. However, it is necessary to remember that these features may not always be present, as shown in one of the cases who did not have a DWI abnormality in this study. This study also investigated whether expanded GGC repeats were translated into polyglycine. Immunohistochemical analysis using a custom antibody raised against putative C-terminal polypeptides followed by polyglycine of uN2CpolyG revealed that polyglycines were localized in the intranuclear inclusions in skin biopsy specimens from all six patients, suggesting its involvement in the pathogenesis of NIID.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37001413"
},
{
- "id": "pmid:8044653",
+ "id": "pmid:36809423",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/8044653",
- "title": "Limited expansion of the (CAG)n repeat of the Huntington gene: a premutation (?).",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/36809423",
+ "title": "Autonomic dysfunction-dominant phenotype in a Chinese family with biallelic GGC repeat expansions in NOTCH2NLC.",
"type": "article-journal",
- "doi": "10.1159/000472340",
+ "doi": "10.1007/s10072-023-06688-x",
"authors": [
- ["E", "Legius"],
- ["H", "Cuppens"],
- ["H", "Dierick"],
- ["K", "Van Zandt"],
- ["R", "Dom"],
- ["J P", "Fryns"],
- ["G", "Evers-Kiebooms"],
- ["M", "Decruyenaere"],
- ["K", "Demyttenaere"],
- ["P", "Marynen"]
+ ["Bin", "Chen"],
+ ["Jing", "Jing"],
+ ["Gehong", "Dong"],
+ ["Yuzhi", "Shi"],
+ ["Cuiping", "Zhang"],
+ ["Yumei", "Zhang"],
+ ["An", "Wang"],
+ ["Hongfei", "Tai"],
+ ["Songtao", "Niu"],
+ ["Xingao", "Wang"],
+ ["Hua", "Pan"],
+ ["Zaiqiang", "Zhang"]
],
- "publisher": "European journal of human genetics : EJHG",
- "issn": "1018-4813",
- "date": "1994-01-01",
- "abstract": "Huntington's disease (HD) is an autosomal dominant disorder with choreic movements, psychiatric manifestations and cognitive dysfunction. Recently the IT15 gene on chromosome 4p has been identified containing an unstable and expanded trinucleotide repeat in patients with HD. We report on the characteristics of this repeat in 248 individuals from 41 Belgian HD families. The length of the expanded repeat was defined precisely and reproducibly on an ALF sequencer and correlated well with the age of onset (r = -0.72). Paternal transmission of the expanded repeat resulted on average in a significantly longer repeat length (+2.79 repeats) than maternal transmission (-0.29 repeats). (CAG)n repeat of a premutation (?) size was observed in this population with subsequent expansion in the disease range. Presymptomatic or prenatal testing using only linked markers may be problematic in these cases.",
+ "publisher": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology",
+ "issn": "1590-3478",
+ "date": "2023-02-21",
+ "abstract": "The GGC repeat expansions in the NOTCH2NLC gene are associated with multiple neurodegenerative disorders. Herein, we report the clinical phenotype in a family with biallelic GGC expansions in NOTCH2NLC. Autonomic dysfunction was a prominent clinical manifestation in three genetically confirmed patients without dementia, parkinsonism, and cerebellar ataxia for\u2009>\u200912\u00a0years. A 7-T brain magnetic resonance imaging in two patients revealed a change in the small cerebral veins. The biallelic GGC repeat expansions may not modify the disease progression in neuronal intranuclear inclusion disease. Autonomic dysfunction-dominant may expand the clinical phenotype of NOTCH2NLC.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8044653"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36809423"
},
{
- "id": "pmid:7888133",
+ "id": "pmid:36715780",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/7888133",
- "title": "Trinucleotide repeat elongation in the huntingtin gene in Huntington's disease patients from 85 French families. The French HD Research Group.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/36715780",
+ "title": "Neuronal intranuclear inclusion disease mimicking progressive supranuclear palsy.",
"type": "article-journal",
- "doi": "",
+ "doi": "10.1007/s10072-023-06644-9",
"authors": [
- ["G", "Lucotte"],
- ["A", "Aouiz\u00e9rate"],
- ["O", "Loreille"],
- ["N", "G\u00e9rard"],
- ["J C", "Turpin"]
+ ["Min", "Tian"],
+ ["Yinlian", "Han"],
+ ["Yiqing", "Bi"],
+ ["Bohan", "Zhang"],
+ ["Ruonan", "Duan"],
+ ["Chengyuan", "Song"],
+ ["Yiming", "Liu"]
],
- "publisher": "Genetic counseling (Geneva, Switzerland)",
- "issn": "1015-8146",
- "date": "1994-01-01",
- "abstract": "IT15 is a new gene encoding a protein named huntingtin; a polymorphic CAG repeat in the proposed open reading frame of IT15 has been characterized, and an elongation of this repeat has been correlated to Huntington's disease (HD). We have investigated the CAG repeat in the huntingtin gene in 85 unrelated French families with Huntington's disease. In 79 patients (from 60 families, where at least one HD DNA was available) we found repeat lengths of 37 to 100 units, in contrast to 11 to 35 CAG's on normal chromosomes. Comparison of repeat length and age at onset of disease symptoms in 71 individuals confirms an inverse correlation (r = -0.51 for p < 10(-4)) between the age at onset and the number of CAG repeat units.",
+ "publisher": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology",
+ "issn": "1590-3478",
+ "date": "2023-01-30",
+ "abstract": "Given the variable nature of clinical manifestations, neuronal intranuclear inclusion disease (NIID) is regarded as a heterogeneous disease which is challenging to diagnose early. To the present, progressive supranuclear palsy (PSP)-like symptoms have never been listed in the performance of NIID.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7888133"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36715780"
},
{
- "id": "pmid:8133508",
+ "id": "pmid:36672065",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/8133508",
- "title": "Gametic but not somatic instability of CAG repeat length in Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/36672065",
+ "title": "Intermediate-Length GGC Repeat Expansion in NOTCH2NLC Was Identified in Chinese Patients with Amyotrophic Lateral Sclerosis.",
"type": "article-journal",
- "doi": "10.1136/jmg.30.12.982",
+ "doi": "10.3390/brainsci13010085",
"authors": [
- ["M E", "MacDonald"],
- ["G", "Barnes"],
- ["J", "Srinidhi"],
- ["M P", "Duyao"],
- ["C M", "Ambrose"],
- ["R H", "Myers"],
- ["J", "Gray"],
- ["P M", "Conneally"],
- ["A", "Young"],
- ["J", "Penney"]
+ ["Mengxia", "Wan"],
+ ["Ji", "He"],
+ ["Junyan", "Huo"],
+ ["Can", "Sun"],
+ ["Yu", "Fu"],
+ ["Dongsheng", "Fan"]
],
- "publisher": "Journal of medical genetics",
- "issn": "0022-2593",
- "date": "1993-12-01",
- "abstract": "Instability of a CAG repeat in 4p16.3 has been found in Huntington's disease (HD) chromosomes. Unlike a similar repeat in the fragile X syndrome, the expanded HD repeat showed no evidence of somatic instability in a comparison of blood, lymphoblast, and brain DNA from the same persons. Four pairs of monozygotic HD twins displayed identical CAG repeat lengths suggesting that repeat size is determined in gametogenesis. In contrast with the fragile X syndrome and with HD somatic tissue, mosaicism was readily detected as a diffuse spread of repeat lengths in DNA from HD sperm samples. Typically, the modal repeat size was larger in the sperm DNA than in corresponding lymphoblast DNA, with the greatest degree of gametic mosaicism coinciding with the longest somatic CAG repeats. These data indicate that the developmental timing of repeat instability appears to differ between HD and fragile X syndrome, and that the fundamental mechanisms leading to repeat expansion may therefore be distinct.",
+ "publisher": "Brain sciences",
+ "issn": "2076-3425",
+ "date": "2023-01-01",
+ "abstract": "GGC repeat expansions in the 5' untranslated region (5'UTR) of the Notch Homolog 2 N-terminal-like C gene (",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8133508"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36672065"
},
{
- "id": "pmid:8133495",
+ "id": "pmid:36545534",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/8133495",
- "title": "A study of the Huntington's disease associated trinucleotide repeat in the Scottish population.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/36545534",
+ "title": "Clinical characteristics of two patients with neuronal intranuclear inclusion disease and literature review.",
"type": "article-journal",
- "doi": "10.1136/jmg.30.12.1003",
+ "doi": "10.3389/fnins.2022.1056261",
"authors": [
- ["L H", "Barron"],
- ["J P", "Warner"],
- ["M", "Porteous"],
- ["S", "Holloway"],
- ["S", "Simpson"],
- ["R", "Davidson"],
- ["D J", "Brock"]
+ ["Bo", "Zhao"],
+ ["Miao", "Yang"],
+ ["Zhiwei", "Wang"],
+ ["Qiqiong", "Yang"],
+ ["Yimo", "Zhang"],
+ ["Xiaokun", "Qi"],
+ ["Shuyi", "Pan"],
+ ["Yingxin", "Yu"]
],
- "publisher": "Journal of medical genetics",
- "issn": "0022-2593",
- "date": "1993-12-01",
- "abstract": "Accurate measurements of a specific CAG repeat sequence in the Huntington's disease (HD) gene in 337 HD patients and 229 normal controls from the Scottish population showed a range from 35 to 62 repeats in affected subjects and eight to 33 in normal subjects. A link between early onset of symptoms and very high repeat number was seen. For HD patients with the most common affected allele sizes (39 to 42 repeats) absolute repeat size was a poor index for the age at onset of symptoms. There was variability in the transmitted repeat size for both sexes in the HD size range. We observed a significant increase of repeat size for paternal transmission of the disease and greater instability for paternally transmitted CAG repeats in the HD size range.",
+ "publisher": "Frontiers in neuroscience",
+ "issn": "1662-4548",
+ "date": "2022-12-05",
+ "abstract": "Neuronal intranuclear inclusion disease (NIID) is a rare chronic progressive neurodegenerative disease, with complex and diverse clinical manifestations and pathological eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous systems and visceral organs. Improvements in diagnostic methods such as skin biopsy and gene testing are helpful in revealing the clinical and genetic characters of NIID.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8133495"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36545534"
},
{
- "id": "pmid:8111374",
+ "id": "pmid:36458450",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/8111374",
- "title": "Mitotic stability and meiotic variability of the (CAG)n repeat in the Huntington disease gene.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/36458450",
+ "title": "Neuropathological features of adult-onset neuronal intranuclear inclusion disease with fluid-attenuated inversion recovery high-intensity signals in the cerebellar paravermal area from an early stage: A case report.",
"type": "article-journal",
- "doi": "10.1093/hmg/2.12.2063",
+ "doi": "10.5414/np301499",
"authors": [
- ["C", "Z\u00fchlke"],
- ["O", "Riess"],
- ["B", "Bockel"],
- ["H", "Lange"],
- ["U", "Thies"]
+ ["Taku", "Homma"],
+ ["Utako", "Nagaoka"],
+ ["Yasuhiro", "Nakata"],
+ ["Jun", "Sone"],
+ ["Asuka", "Funai"],
+ ["Aki", "Murayama"],
+ ["Cisato", "Tamai"],
+ ["Takashi", "Komori"],
+ ["Kazushi", "Takahashi"]
],
- "publisher": "Human molecular genetics",
- "issn": "0964-6906",
- "date": "1993-12-01",
- "abstract": "The gene causing Huntington's disease, an autosomal dominantly inherited, neurodegenerative disorder, has been identified recently. The corresponding mutation is involving an expansion in the number of (CAG)n repeats in the coding region of the Huntington's disease gene on chromosome 4. In this report, we demonstrate the length variation of the repeat in 513 non-HD chromosomes from normal individuals and HD patients showing 23 alleles with 11 to 33 repeats. Analyzing the inheritance of the (CAG)n stretch we found meiotic instability for HD alleles ([CAG]40 to [CAG]75) with a mutation frequency of approximately 0.7, while in 431 meioses of normal alleles only two expansions were identified. The risk of expansion during spermatogenesis is enhanced compared to oogenesis explaining juvenile onset by transmission from affected fathers. Further, the number of (CAG)n copies in an affected individual in relation to the sex of the transmitting parent was evaluated and no significant differences were found. No mosaicism or differences in the repeat lengths were observed in the DNA from different tissues including brain and lymphocytes of two HD patients indicating mitotic stability of the mutation. Therefore, the determination of the repeat number in the DNA of blood lymphocytes is probably representative of all tissues in a patient.",
+ "publisher": "Clinical neuropathology",
+ "issn": "0722-5091",
+ "date": "2023-01-01",
+ "abstract": "Neuronal intranuclear inclusion disease (NIID) is a neurological disorder characterized by eosinophilic intranuclear inclusions (INI) in systemic organs and various cell types. High-intensity signals along the corticomedullary junction on diffusion-weighted imaging and presence of cellular p62-INI in skin biopsy are known indicators for NIID. Furthermore, GGC repeat expansion in",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8111374"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36458450"
},
{
- "id": "pmid:8252042",
+ "id": "pmid:36207023",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/8252042",
- "title": "De novo expansion of a (CAG)n repeat in sporadic Huntington's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/36207023",
+ "title": "",
"type": "article-journal",
- "doi": "10.1038/ng1093-168",
+ "doi": "10.1136/svn-2022-001631",
"authors": [
- ["R H", "Myers"],
- ["M E", "MacDonald"],
- ["W J", "Koroshetz"],
- ["M P", "Duyao"],
- ["C M", "Ambrose"],
- ["S A", "Taylor"],
- ["G", "Barnes"],
- ["J", "Srinidhi"],
- ["C S", "Lin"],
- ["W L", "Whaley"]
+ ["Yun-Chao", "Wang"],
+ ["Yu", "Fan"],
+ ["Wen-Kai", "Yu"],
+ ["Si", "Shen"],
+ ["Jia-Di", "Li"],
+ ["Yuan", "Gao"],
+ ["Yan", "Ji"],
+ ["Yu-Sheng", "Li"],
+ ["Lu-Lu", "Yu"],
+ ["Zi-Chen", "Zhao"],
+ ["Shan-Shan", "Li"],
+ ["Yao", "Ding"],
+ ["Chang-He", "Shi"],
+ ["Yu-Ming", "Xu"]
],
- "publisher": "Nature genetics",
- "issn": "1061-4036",
- "date": "1993-10-01",
- "abstract": "Huntington's disease (HD) chromosomes contain an expanded unstable (CAG)n repeat in chromosome 4p16.3. We have examined nine families with potential de novo expression of the disease. With one exception, all of the affected individuals had 42 or more repeat units, well above the normal range. In four families, elderly unaffected relatives inherited the same chromosome as that containing the expanded repeat in the proband, but had repeat lengths of 34-38 units, spanning the gap between the normal and HD distributions. Thus, mutation to HD is usually associated with an expansion from an already large repeat.",
+ "publisher": "Stroke and vascular neurology",
+ "issn": "2059-8696",
+ "date": "2022-10-07",
+ "abstract": "GGC repeat expansions in the human-specific",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8252042"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36207023"
},
{
- "id": "pmid:8242074",
+ "id": "pmid:36191230",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/8242074",
- "title": "Trinucleotide repeat elongation in the Huntingtin gene in Huntington disease patients from 71 Danish families.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/36191230",
+ "title": "CGG repeat expansion in",
"type": "article-journal",
- "doi": "10.1093/hmg/2.9.1475",
+ "doi": "10.1073/pnas.2208649119",
"authors": [
- ["A", "N\u00f8rrem\u00f8lle"],
- ["O", "Riess"],
- ["J T", "Epplen"],
- ["K", "Fenger"],
- ["L", "Hasholt"],
- ["S A", "S\u00f8rensen"]
+ ["Jiaxi", "Yu"],
+ ["Tongling", "Liufu"],
+ ["Yilei", "Zheng"],
+ ["Jin", "Xu"],
+ ["Lingchao", "Meng"],
+ ["Wei", "Zhang"],
+ ["Yun", "Yuan"],
+ ["Daojun", "Hong"],
+ ["Nicolas", "Charlet-Berguerand"],
+ ["Zhaoxia", "Wang"],
+ ["Jianwen", "Deng"]
],
- "publisher": "Human molecular genetics",
- "issn": "0964-6906",
- "date": "1993-09-01",
- "abstract": "IT15 is a novel gene, localized to chromosome 4, and encoding a protein named Huntingtin. A polymorphic CAG repeat in the proposed open reading frame of IT15 has been characterized, and an elongation of this repeat has been correlated to Huntington's Disease. We have investigated the CAG repeat in the Huntingtin gene in 71 unrelated Danish patients with Huntington's Disease, and found repeat lengths of 39 to 70 repeat units in contrast to 9 to 30 CAG's on normal chromosomes. Comparison of repeat length and age at onset of disease symptoms in 52 individuals indicates an inverse correlation between the age at onset and the number of CAG repeat units.",
+ "publisher": "Proceedings of the National Academy of Sciences of the United States of America",
+ "issn": "1091-6490",
+ "date": "2022-10-03",
+ "abstract": "Neuronal intranuclear inclusion disease (NIID) is a neuromuscular/neurodegenerative disease caused by the expansion of CGG repeats in the 5' untranslated region (UTR) of the",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8242074"
-},
-{
- "id": "pmid:8401589",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/8401589",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:8401589']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36191230"
},
{
- "id": "pmid:2971929",
+ "id": "pmid:36172483",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/2971929",
- "title": "Construction of a NotI linking library and isolation of new markers close to the Huntington's disease gene.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/36172483",
+ "title": "Urine cytological study in patients with clinicopathologically confirmed neuronal intranuclear inclusion disease.",
"type": "article-journal",
- "doi": "10.1093/nar/16.19.9185",
+ "doi": "10.3389/fnagi.2022.977604",
"authors": [
- ["T M", "Pohl"],
- ["M", "Zimmer"],
- ["M E", "MacDonald"],
- ["B", "Smith"],
- ["M", "Bucan"],
- ["A", "Poustka"],
- ["S", "Volinia"],
- ["S", "Searle"],
- ["G", "Zehetner"],
- ["J J", "Wasmuth"]
+ ["Yiyi", "Zhou"],
+ ["Pengcheng", "Huang"],
+ ["Zhaojun", "Huang"],
+ ["Yun", "Peng"],
+ ["Yilei", "Zheng"],
+ ["Yaqing", "Yu"],
+ ["Min", "Zhu"],
+ ["Jianwen", "Deng"],
+ ["Zhaoxia", "Wang"],
+ ["Daojun", "Hong"]
],
- "publisher": "Nucleic acids research",
- "issn": "0305-1048",
- "date": "1988-10-11",
- "abstract": "Linking clones contain sequences flanking recognition sites for enzymes cutting rarely in mammalian DNA. They can be used to obtain and correlate both physical and genetic mapping information over subregions of mammalian chromosomes. We have constructed and used a NotI linking clone library representing unmethylated NotI sites from HHW693 DNA, a hamster hybrid cell line containing 4p15-4pter and a fragment of 5p as its only human chromosome contribution. Human clones were identified by hybridisation with a cloned human repeat sequence, and localised further to subregions of human chromosome 4p15-4pter using a panel of additional hybrids. Clones from the region distal to the DNA probes (D4S10, D4S43, D4S95) linked to the Huntington's disease mutation, were further analysed. Four markers close to the HD gene: D4S111, D4S113, D4S114 and clone 417 are described here. In addition to serving as markers in physical and genetic mapping experiments, these linking clones provide probes next to cleavable NotI sites, and can therefore be used to screen NotI based chromosome jumping libraries. They also provide indications for potential gene sequences, identifiable as evolutionarily conserved sequences.",
+ "publisher": "Frontiers in aging neuroscience",
+ "issn": "1663-4365",
+ "date": "2022-09-12",
+ "abstract": "The diagnosis of neuronal intranuclear inclusion disease (NIID) is currently based on CGG repeat expansion in the 5'UTR of the",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:2971929"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36172483"
},
{
- "id": "pmid:3131233",
+ "id": "pmid:36041634",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/3131233",
- "title": "Absence of B-cell or T-cell clonal expansion in nodular, lymphocyte predominant Hodgkin's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/36041634",
+ "title": "Patients with biallelic GGC repeat expansions in NOTCH2NLC exhibiting a typical neuronal intranuclear inclusion disease phenotype.",
"type": "article-journal",
- "doi": "10.1016/s0046-8177(88)80210-7",
+ "doi": "10.1016/j.ygeno.2022.110469",
"authors": [
- ["M D", "Linden"],
- ["A J", "Fishleder"],
- ["W E", "Katzin"],
- ["R R", "Tubbs"]
+ ["Shinichi", "Kameyama"],
+ ["Takeshi", "Mizuguchi"],
+ ["Hiroshi", "Doi"],
+ ["Shigeru", "Koyano"],
+ ["Masaki", "Okubo"],
+ ["Mikiko", "Tada"],
+ ["Hiroshi", "Shimizu"],
+ ["Hiromi", "Fukuda"],
+ ["Naomi", "Tsuchida"],
+ ["Yuri", "Uchiyama"],
+ ["Eriko", "Koshimizu"],
+ ["Kohei", "Hamanaka"],
+ ["Atsushi", "Fujita"],
+ ["Kazuharu", "Misawa"],
+ ["Satoko", "Miyatake"],
+ ["Kazuaki", "Kanai"],
+ ["Fumiaki", "Tanaka"],
+ ["Naomichi", "Matsumoto"]
],
- "publisher": "Human pathology",
- "issn": "0046-8177",
- "date": "1988-05-01",
- "abstract": "Recent studies based upon immunophenotypic data have provided strong evidence that nodular lymphocyte predominant Hodgkin's disease (NLPHD) represents an entity that is distinct from other subtypes of Hodgkin's disease (HD). In contract to other forms of HD, the predominance of B-lymphocytes in NLPHD has prompted the thesis that this lesion is actually an atypical B-cell hyperplasia or follicular center cell lymphoma. Three cases of NLPHD by restriction endonuclease analysis were studied in an attempt to identify a clonal B-cell or T-cell expansion in this disorder. DNA was extracted from these tumors and hybridized to probes for the immunoglobulin genes (C kappa, C lambda, JH) and the T-cell receptor beta chain gene. Gene rearrangements were not detectable in any of the cases. The results provide genotypic evidence that there is not a monoclonal or oligoclonal proliferation of small B-lymphocytes or T-lymphocytes in NLPHD. The possibility that the L&H Reed-Sternberg cells are monoclonal cannot be excluded because their small number is below the level of sensitivity of this technique.",
+ "publisher": "Genomics",
+ "issn": "1089-8646",
+ "date": "2022-08-27",
+ "abstract": "We report two patients with autosomal dominant neuronal intranuclear inclusion disease (NIID) harboring the biallelic GGC repeat expansion in NOTCH2NLC to uncover the impact of repeat expansion zygosity on the clinical phenotype. The zygosity of the entire NOTCH2NLC GGC repeat expansion and DNA methylation were comprehensively evaluated using fluorescent amplicon length PCR (AL-PCR), Southern blotting and targeted long-read sequencing, and detailed genetic/epigenetic and clinical features were described. In AL-PCR, we could not recognize the wild-type allele in both patients. Targeted long-read sequencing revealed that one patient harbored a homozygous repeat expansion. The other patient harbored compound heterozygous repeat expansions. The GGC repeats and the nearest CpG island were hypomethylated in all expanded alleles in both patients. Both patients harboring the biallelic GGC repeat expansion showed a typical dementia-dominant NIID phenotype. In conclusion, the biallelic GGC repeat expansion in two typical NIID patients indicated that NOTCH2NLC-related diseases could be completely dominant.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:3131233"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36041634"
},
{
- "id": "pmid:38948793",
+ "id": "pmid:36033605",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/38948793",
- "title": "NMR structures of small molecules bound to a model of an RNA CUG repeat expansion.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/36033605",
+ "title": "Case report: Adult-onset neuronal intranuclear inclusion disease with an amyotrophic lateral sclerosis phenotype.",
"type": "article-journal",
- "doi": "10.1101/2024.06.21.600119",
+ "doi": "10.3389/fnins.2022.960680",
"authors": [
- ["Jonathan L", "Chen"],
- ["Amirhossein", "Taghavi"],
- ["Alexander J", "Frank"],
- ["Matthew A", "Fountain"],
- ["Shruti", "Choudhary"],
- ["Soma", "Roy"],
- ["Jessica L", "Childs-Disney"],
- ["Matthew D", "Disney"]
+ ["Masako", "Fujita"],
+ ["Tatsuya", "Ueno"],
+ ["Yasuo", "Miki"],
+ ["Akira", "Arai"],
+ ["Hidekachi", "Kurotaki"],
+ ["Koichi", "Wakabayashi"],
+ ["Masahiko", "Tomiyama"]
],
- "publisher": "bioRxiv : the preprint server for biology",
- "issn": "2692-8205",
- "date": "2024-06-22",
- "abstract": "Trinucleotide repeat expansions fold into long, stable hairpins and cause a variety of incurable RNA gain-of-function diseases such as Huntington's disease, the myotonic dystrophies, and spinocerebellar ataxias. One approach for treating these diseases is to bind small molecules to the structured RNAs. Both Huntington's disease-like 2 (HDL2) and myotonic dystrophy type 1 (DM1) are caused by a r(CUG) repeat expansion, or r(CUG)",
+ "publisher": "Frontiers in neuroscience",
+ "issn": "1662-4548",
+ "date": "2022-08-10",
+ "abstract": "Amyotrophic lateral sclerosis (ALS) is one of the differential diagnoses of diseases that occur in adulthood and lead to progressive generalized muscle weakness. Neuronal intranuclear inclusion disease (NIID) is a disease in which histopathologically eosinophilic nuclear inclusion bodies are found in various systems. Both familial and sporadic forms of the disease have been reported. Most cases of sporadic NIID are of the dementia type, in which the main symptom is dementia at the first onset. Familial NIID is more diverse, with the main dominant symptoms being muscle weakness (NIID-M), dementia (NIID-D), and parkinsonism (NIID-P). Furthermore, recently, a GGC-repeat expansion in the Notch 2 N-terminal like C (",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38948793"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36033605"
},
{
- "id": "pmid:29208631",
+ "id": "pmid:35866887",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/29208631",
- "title": "The",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/35866887",
+ "title": "Profiling the NOTCH2NLC GGC Repeat Expansion in Parkinson's Disease in the European Population.",
"type": "article-journal",
- "doi": "10.1242/dmm.029082",
+ "doi": "10.1002/mds.29155",
"authors": [
- ["Eduardo", "Calpena"],
- ["V\u00edctor", "L\u00f3pez Del Amo"],
- ["Mouli", "Chakraborty"],
- ["Beatriz", "Llamus\u00ed"],
- ["Rub\u00e9n", "Artero"],
- ["Carmen", "Espin\u00f3s"],
- ["M\u00e1ximo I", "Galindo"]
+ ["Kimberley J", "Billingsley"],
+ ["Pilar", "Alvarez Jerez"],
+ ["Francis P", "Grenn"],
+ ["Sara", "Bandres-Ciga"],
+ ["Laksh", "Malik"],
+ ["Dena", "Hernandez"],
+ ["Ali", "Torkamani"],
+ ["Mina", "Ryten"],
+ ["John", "Hardy"],
+ ["Sonja W", "Scholz"],
+ ["Bryan J", "Traynor"],
+ ["Clifton L", "Dalgard"],
+ ["Debra J", "Ehrlich"],
+ ["Toshiko", "Tanaka"],
+ ["Luigi", "Ferrucci"],
+ ["Thomas G", "Beach"],
+ ["Geidy E", "Serrano"],
+ ["Jinhui", "Ding"],
+ ["J Raphael", "Gibbs"],
+ ["Cornelis", "Blauwendraat"],
+ ["Andrew B", "Singleton"]
],
- "publisher": "Disease models & mechanisms",
- "issn": "1754-8411",
- "date": "2018-01-17",
- "abstract": "Members of the Junctophilin (JPH) protein family have emerged as key actors in all excitable cells, with crucial implications for human pathophysiology. In mammals, this family consists of four members (JPH1-JPH4) that are differentially expressed throughout excitable cells. The analysis of knockout mice lacking JPH subtypes has demonstrated their essential contribution to physiological functions in skeletal and cardiac muscles and in neurons. Moreover, mutations in the human",
+ "publisher": "Movement disorders : official journal of the Movement Disorder Society",
+ "issn": "1531-8257",
+ "date": "2022-07-22",
+ "abstract": "",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29208631"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35866887"
},
{
- "id": "pmid:22447335",
+ "id": "pmid:35419641",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/22447335",
- "title": "JPH3 repeat expansions cause a progressive akinetic-rigid syndrome with severe dementia and putaminal rim in a five-generation African-American family.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/35419641",
+ "title": "Adult-onset autosomal dominant leukodystrophy and neuronal intranuclear inclusion disease: lessons from two new Chinese families.",
"type": "article-journal",
- "doi": "10.1007/s10048-012-0318-9",
+ "doi": "10.1007/s10072-022-06057-0",
"authors": [
- ["Susanne A", "Schneider"],
- ["Kate E", "Marshall"],
- ["Jianfeng", "Xiao"],
- ["Mark S", "LeDoux"]
+ ["Shuai", "Chen"],
+ ["Jin-Long", "Zou"],
+ ["Shuang", "He"],
+ ["Wei", "Li"],
+ ["Jie-Wen", "Zhang"],
+ ["Shu-Jian", "Li"]
],
- "publisher": "Neurogenetics",
- "issn": "1364-6753",
- "date": "2012-03-25",
- "abstract": "We report the clinical, neuropsychological, genetic, and radiological features of a large five-generation African-American kindred from the southern USA presenting with a progressive akinetic-rigid syndrome and severe dementia, but clinically insignificant chorea, due to mutations in junctophillin 3 (JPH3). Overt disease onset was in the mid-20s to late 30s with cognitive decline, REM sleep disturbance, or psychiatric features, followed by development of a levodopa-unresponsive akinetic-rigid motor syndrome. Dystonia and myoclonus were present in some subjects. A bedridden, nonverbal severely akinetic-rigid state developed within 10 to 15 years after onset. CTG repeat expansions ranged from 47 to 53. Imaging revealed generalized cerebral atrophy with severe striatal involvement and putaminal rim hyperintensity. Analysis of our kindred indicates that JPH3 mutations should be considered in the differential diagnosis of early-onset dementia and hypokinetic-rigid syndromes in individuals of African descent. Moreover, chorea may not be overtly manifest at presentation or during significant parts of the disease course.",
+ "publisher": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology",
+ "issn": "1590-3478",
+ "date": "2022-04-14",
+ "abstract": "Adult-onset autosomal dominant leukodystrophy (ADLD) is a rare genetic leukoencephalopathy caused by duplication of the lamin B1 gene (LMNB1) or LMNB1 upstream deletions. Neuronal intranuclear inclusion disease (NIID) is another leukoencephalopathy due to GGC repeat expansion in the 5'-untranslated region of the NOTCH2NLC gene. Here, we report two Chinese ADLD families with neuroimaging and clinical features mimicking NIID.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22447335"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35419641"
},
{
- "id": "pmid:14557581",
+ "id": "pmid:35411397",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/14557581",
- "title": "Huntington's disease--like 2 can present as chorea-acanthocytosis.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/35411397",
+ "title": "Neuronal intranuclear inclusion disease in patients with adult-onset non-vascular leukoencephalopathy.",
"type": "article-journal",
- "doi": "10.1212/01.wnl.0000085866.68470.6d",
+ "doi": "10.1093/brain/awac135",
"authors": [
- ["R H", "Walker"],
- ["A", "Rasmussen"],
- ["D", "Rudnicki"],
- ["S E", "Holmes"],
- ["E", "Alonso"],
- ["T", "Matsuura"],
- ["T", "Ashizawa"],
- ["B", "Davidoff-Feldman"],
- ["R L", "Margolis"]
+ ["Yi Hong", "Liu"],
+ ["Ying Tsen", "Chou"],
+ ["Fu Pang", "Chang"],
+ ["Wei Ju", "Lee"],
+ ["Yuh Cherng", "Guo"],
+ ["Cheng Ta", "Chou"],
+ ["Hui Chun", "Huang"],
+ ["Takeshi", "Mizuguchi"],
+ ["Chien Chen", "Chou"],
+ ["Hsiang Yu", "Yu"],
+ ["Kai Wei", "Yu"],
+ ["Hsiu Mei", "Wu"],
+ ["Pei Chien", "Tsai"],
+ ["Naomichi", "Matsumoto"],
+ ["Yi Chung", "Lee"],
+ ["Yi Chu", "Liao"]
],
- "publisher": "Neurology",
- "issn": "1526-632X",
- "date": "2003-10-14",
- "abstract": "Three patients from a previously described family with autosomal dominant chorea-acanthocytosis were found to have the CTG trinucleotide repeat expansion mutation of the junctophilin-3 gene associated with Huntington's disease-like 2 (HDL2). One of six previously identified patients with HDL2 had acanthocytosis on peripheral blood smear, suggesting that HDL2 should be considered in the differential of chorea-acanthocytosis.",
+ "publisher": "Brain : a journal of neurology",
+ "issn": "1460-2156",
+ "date": "2022-09-14",
+ "abstract": "Neuronal intranuclear inclusion disease (NIID), caused by an expansion of GGC repeats in the 5'-untranslated region of NOTCH2NLC, is an important but underdiagnosed cause of adult-onset leukoencephalopathies. The present study aimed to investigate the prevalence, clinical spectrum and brain MRI characteristics of NIID in adult-onset nonvascular leukoencephalopathies and assess the diagnostic performance of neuroimaging features. One hundred and sixty-one unrelated Taiwanese patients with genetically undetermined nonvascular leukoencephalopathies were screened for the NOTCH2NLC GGC repeat expansions using fragment analysis, repeat-primed PCR, Southern blot analysis and/or nanopore sequencing with Cas9-mediated enrichment. Among them, 32 (19.9%) patients had an expanded NOTCH2NLC allele and were diagnosed with NIID. We enrolled another two affected family members from one patient for further analysis. The size of the expanded NOTCH2NLC GGC repeats in the 34 patients ranged from 73 to 323 repeats. Skin biopsies from five patients all showed eosinophilic, p62-positive intranuclear inclusions in the sweat gland cells and dermal adipocytes. Among the 34 NIID patients presenting with nonvascular leukoencephalopathies, the median age at symptom onset was 61 years (range, 41-78 years) and the initial presentations included cognitive decline (44.1%; 15/34), acute encephalitis-like episodes (32.4%; 11/34), limb weakness (11.8%; 4/34) and parkinsonism (11.8%; 4/34). Cognitive decline (64.7%; 22/34) and acute encephalitis-like episodes (55.9%; 19/34) were also the most common overall manifestations. Two-thirds of the patients had either bladder dysfunction or visual disturbance. Comparing the brain MRI features between the NIID patients and individuals with other undetermined leukoencephalopathies, corticomedullary junction curvilinear lesions on diffusion weighted images were the best biomarkers for diagnosing NIID with high specificity (98.4%) and sensitivity (88.2%). However, this diffusion weighted imaging abnormality was absent in 11.8% of the NIID patients. When only fluid-attenuated inversion recovery images were available, the presence of white matter hyperintensity lesions either in the paravermis or middle cerebellar peduncles also favoured the diagnosis of NIID with a specificity of 85.3% and sensitivity of 76.5%. Among the MRI scans of 10 patients, performed within 5 days of the onset of acute encephalitis-like episodes, five showed cortical hyperintense lesions on diffusion weighted images and two revealed focal brain oedema. In conclusion, NIID accounts for 19.9% (32/161) of patients with adult-onset genetically undiagnosed nonvascular leukoencephalopathies in Taiwan. Half of the NIID patients developed encephalitis-like episodes with restricted diffusion in the cortical regions on diffusion weighted images at the acute stage. Corticomedullary junction hyperintense lesions, white matter hyperintensities in the paravermis or middle cerebellar peduncles, bladder dysfunction and visual disturbance are useful hints to diagnosing NIID.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:14557581"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35411397"
},
{
- "id": "pmid:36052448",
+ "id": "pmid:35147270",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/36052448",
- "title": "Expanded clinical spectrum of oculopharyngodistal myopathy type 1.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/35147270",
+ "title": "The role of NOTCH2NLC in Parkinson's disease: A clinical, neuroimaging, and pathological study.",
"type": "article-journal",
- "doi": "10.1002/mus.27717",
+ "doi": "10.1111/ene.15283",
"authors": [
- ["Takahiro", "Shimizu"],
- ["Hiroyuki", "Ishiura"],
- ["Manato", "Hara"],
- ["Shota", "Shibata"],
- ["Atsushi", "Unuma"],
- ["Akatsuki", "Kubota"],
- ["Kaori", "Sakuishi"],
- ["Kiyoharu", "Inoue"],
- ["Jun", "Goto"],
- ["Yuji", "Takahashi"],
- ["Yuichiro", "Shirota"],
- ["Masashi", "Hamada"],
- ["Jun", "Shimizu"],
- ["Shoji", "Tsuji"],
- ["Tatsushi", "Toda"]
+ ["Peng", "Liu"],
+ ["Dehao", "Yang"],
+ ["Fan", "Zhang"],
+ ["Shuqi", "Chen"],
+ ["Fei", "Xie"],
+ ["Yong", "Luo"],
+ ["Haotian", "Wang"],
+ ["Yueting", "Chen"],
+ ["Zhiru", "Lin"],
+ ["Lebo", "Wang"],
+ ["Xinhui", "Chen"],
+ ["Bo", "Wang"],
+ ["Sheng", "Wu"],
+ ["Zhiyuan", "Ouyang"],
+ ["Zhidong", "Cen"],
+ ["Wei", "Luo"]
],
- "publisher": "Muscle & nerve",
- "issn": "1097-4598",
- "date": "2022-09-27",
- "abstract": "Heterozygous CGG repeat expansions in low-density lipoprotein receptor-related protein 12 (LRP12) have recently been identified as a cause of oculopharyngodistal myopathy (OPDM), and the disease is designated as OPDM type 1 (OPDM1). In contrast to broadening of our knowledge on the genetic background of OPDM, what we know of the clinical phenotype of genetically confirmed OPDM1 remains limited.",
+ "publisher": "European journal of neurology",
+ "issn": "1468-1331",
+ "date": "2022-03-03",
+ "abstract": "Recently, the pathogenic and intermediate GGC repeat expansion in NOTCH2NLC was detected in Parkinson's disease (PD). However, detailed clinical, neuroimaging, and pathological information of clinically diagnosed PD patients with pathogenic GGC repeat expansion in NOTCH2NLC remains scarce. Thus, we aimed to elucidate the clinical, neuroimaging, and pathological characteristics of PD patients carrying the pathogenic GGC repeat expansion in NOTCH2NLC.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36052448"
-},
-{
- "id": "pmid:32493488",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/32493488",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:32493488']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35147270"
},
{
- "id": "pmid:27072820",
+ "id": "pmid:34797461",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/27072820",
- "title": "MLVA and MLST typing of Brucella from Qinghai, China.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/34797461",
+ "title": "Characteristics of ocular findings of patients with neuronal intranuclear inclusion disease.",
"type": "article-journal",
- "doi": "10.1186/s40249-016-0123-z",
+ "doi": "10.1007/s10072-021-05748-4",
"authors": [
- ["Jun-Ying", "Ma"],
- ["Hu", "Wang"],
- ["Xue-Fei", "Zhang"],
- ["Li-Qing", "Xu"],
- ["Gui-Ying", "Hu"],
- ["Hai", "Jiang"],
- ["Fang", "Zhao"],
- ["Hong-Yan", "Zhao"],
- ["Dong-Ri", "Piao"],
- ["Yu-Min", "Qin"],
- ["Bu-Yun", "Cui"],
- ["Gong-Hua", "Lin"]
+ ["Chang", "Liu"],
+ ["Xinghua", "Luan"],
+ ["Xiaohong", "Liu"],
+ ["Xiangning", "Wang"],
+ ["Xuan", "Cai"],
+ ["Tingting", "Li"],
+ ["Li", "Cao"],
+ ["Da", "Long"]
],
- "publisher": "Infectious diseases of poverty",
- "issn": "2049-9957",
- "date": "2016-04-13",
- "abstract": "The Qinghai-Tibet Plateau (QTP) of China is an extensive pastoral and semi-pastoral area, and because of poverty and bad hygiene conditions, Brucella is highly prevalent in this region. In order to adequately prevent this disease in the QTP region it is important to determine the identity of Brucella species that caused the infection.",
+ "publisher": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology",
+ "issn": "1590-3478",
+ "date": "2021-11-19",
+ "abstract": "This study aimed to explore the ocular characteristics of neuronal intranuclear inclusion disease (NIID), caused by GGC repeat expansion in the NOTCH2NLC gene, combined with the systemic clinical manifestations, and propose early diagnostic features of NIID.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27072820"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34797461"
},
{
- "id": "pmid:39848530",
+ "id": "pmid:34774111",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/39848530",
- "title": "Phenotypic Heterogeneity of ADTKD-MUC1 Diagnosed Using VNtyper, a Novel Genetic Technique.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/34774111",
+ "title": "Father-to-offspring transmission of extremely long NOTCH2NLC repeat expansions with contractions: genetic and epigenetic profiling with long-read sequencing.",
"type": "article-journal",
- "doi": "10.1053/j.ajkd.2024.11.010",
+ "doi": "10.1186/s13148-021-01192-5",
"authors": [
- ["Jessica", "Kachmar"],
- ["Hassan", "Saei"],
- ["Vincent", "Morini\u00e8re"],
- ["Laurence", "Heidet"],
- ["Bertrand", "Knebelmann"],
- ["Olivier", "Gribouval"],
- ["Manon", "Mautret-Godefroy"],
- ["St\u00e9phane", "Burtey"],
- ["Vincent", "Vuiblet"],
- ["Asma", "Alla"],
- ["Axel", "Ibalanky"],
- ["Olivier", "Moranne"],
- ["Mathilde", "Nizon"],
- ["Benjamin", "Savenkoff"],
- ["Patrick", "Nitschk\u00e9"],
- ["Corinne", "Antignac"],
- ["Guillaume", "Dorval"]
+ ["Hiromi", "Fukuda"],
+ ["Daisuke", "Yamaguchi"],
+ ["Kristofor", "Nyquist"],
+ ["Yasushi", "Yabuki"],
+ ["Satoko", "Miyatake"],
+ ["Yuri", "Uchiyama"],
+ ["Kohei", "Hamanaka"],
+ ["Ken", "Saida"],
+ ["Eriko", "Koshimizu"],
+ ["Naomi", "Tsuchida"],
+ ["Atsushi", "Fujita"],
+ ["Satomi", "Mitsuhashi"],
+ ["Kazuyuki", "Ohbo"],
+ ["Yuki", "Satake"],
+ ["Jun", "Sone"],
+ ["Hiroshi", "Doi"],
+ ["Keisuke", "Morihara"],
+ ["Tomoko", "Okamoto"],
+ ["Yuji", "Takahashi"],
+ ["Aaron M", "Wenger"],
+ ["Norifumi", "Shioda"],
+ ["Fumiaki", "Tanaka"],
+ ["Naomichi", "Matsumoto"],
+ ["Takeshi", "Mizuguchi"]
],
- "publisher": "American journal of kidney diseases : the official journal of the National Kidney Foundation",
- "issn": "1523-6838",
- "date": "2025-01-22",
- "abstract": "Molecular diagnosis of autosomal dominant tubulointerstitial kidney disease (ADTKD) due to variants in the MUC1 gene has long been challenging because variants lie in a large variable number of tandem repeat (VNTR) region, making identification impossible using standard short-read techniques. Previously, we addressed this diagnostic limitation by developing a computational pipeline named VNtyper for easier reliable detection of MUC1 VNTR pathogenic variants from short-read sequences. This led to unexpected diagnoses of ADTKD-MUC1 among patients with kidney disease referred for genetic testing, which we report here.",
+ "publisher": "Clinical epigenetics",
+ "issn": "1868-7083",
+ "date": "2021-11-13",
+ "abstract": "GGC repeat expansions in NOTCH2NLC are associated with neuronal intranuclear inclusion disease. Very recently, asymptomatic carriers with NOTCH2NLC repeat expansions were reported. In these asymptomatic individuals, the CpG island in NOTCH2NLC is hypermethylated, suggesting that two factors repeat length and DNA methylation status should be considered to evaluate pathogenicity. Long-read sequencing can be used to simultaneously profile genomic and epigenomic alterations. We analyzed four sporadic cases with NOTCH2NLC repeat expansion and their phenotypically normal parents. The native genomic DNA that retains base modification was sequenced on a per-trio basis using both PacBio and Oxford Nanopore long-read sequencing technologies. A custom workflow was developed to evaluate DNA modifications. With these two technologies combined, long-range DNA methylation information was integrated with complete repeat DNA sequences to investigate the genetic origins of expanded GGC repeats in these sporadic cases.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39848530"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34774111"
},
{
- "id": "pmid:39576755",
+ "id": "pmid:34392981",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/39576755",
- "title": "Unraveling",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/34392981",
+ "title": "Analysis of NOTCH2NLC GGC repeat expansion in Taiwanese patients with amyotrophic lateral sclerosis.",
"type": "article-journal",
- "doi": "10.1021/acs.analchem.4c02011",
+ "doi": "10.1016/j.neurobiolaging.2021.07.011",
"authors": [
- ["Amanda", "Helms"],
- ["Vincent", "Chang"],
- ["Stacy A", "Malaker"],
- ["Jennifer S", "Brodbelt"]
+ ["Kang-Yang", "Jih"],
+ ["Ying-Tsen", "Chou"],
+ ["Pei-Chien", "Tsai"],
+ ["Yi-Chu", "Liao"],
+ ["Yi-Chung", "Lee"]
],
- "publisher": "Analytical chemistry",
- "issn": "1520-6882",
- "date": "2024-11-22",
- "abstract": "Deciphering the pattern and abundance of",
+ "publisher": "Neurobiology of aging",
+ "issn": "1558-1497",
+ "date": "2021-07-23",
+ "abstract": "The GGC repeat expansion in the 5'-untranslated region of NOTCH2NLC was recently identified as the cause of neuronal intranuclear inclusion disease (NIID). To determine if the NIID repeat expansion contributes to amyotrophic lateral sclerosis (ALS), we screened 304 unrelated ALS patients and 637 healthy controls for the GGC repeat expansion in NOTCH2NLC using repeat-primed PCR and fragment analysis. None of the ALS patients carried the GGC repeat expansion. The sizes of the GGC repeats ranged from 7 to 36 in the ALS patients and 4 to 46 in the controls. The distribution of the GGC repeat sizes did not differ between the two groups. Our findings indicate that the NOTCH2NLC GGC repeat expansion is absent or extremely rare in Taiwanese patients with ALS.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39576755"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34392981"
},
{
- "id": "pmid:39325540",
+ "id": "pmid:34306035",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/39325540",
- "title": "Systematic Screening of Autosomal Dominant Tubulointerstitial Kidney Disease- MUC1 27dupC Pathogenic Variant through Exome Sequencing.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/34306035",
+ "title": "GGC Repeat Expansion in the",
"type": "article-journal",
- "doi": "10.1681/asn.0000000503",
+ "doi": "10.3389/fgene.2021.694790",
"authors": [
- ["Ilias", "Bensouna"],
- ["Thomas", "Robert"],
- ["Xavier", "Vanhoye"],
- ["Marine", "Dancer"],
- ["Laure", "Raymond"],
- ["Pierre", "Delaug\u00e8re"],
- ["Pascale", "Hilbert"],
- ["Hugues", "Richard"],
- ["Laurent", "Mesnard"]
+ ["Hui", "Wang"],
+ ["Jiaxi", "Yu"],
+ ["Meng", "Yu"],
+ ["Jianwen", "Deng"],
+ ["Wei", "Zhang"],
+ ["He", "Lv"],
+ ["Jing", "Liu"],
+ ["Xin", "Shi"],
+ ["Wei", "Liang"],
+ ["Zhirong", "Jia"],
+ ["Daojun", "Hong"],
+ ["Lingchao", "Meng"],
+ ["Zhaoxia", "Wang"],
+ ["Yun", "Yuan"]
],
- "publisher": "Journal of the American Society of Nephrology : JASN",
- "issn": "1533-3450",
- "date": "2024-09-26",
- "abstract": "",
+ "publisher": "Frontiers in genetics",
+ "issn": "1664-8021",
+ "date": "2021-07-07",
+ "abstract": "There is still a considerable proportion of patients with inherited peripheral neuropathy (IPN) whose pathogenic genes are unknown. This study was intended to investigate whether the GGC repeat expansion in the",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39325540"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34306035"
},
{
- "id": "pmid:37456840",
+ "id": "pmid:33871559",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/37456840",
- "title": "VNtyper enables accurate alignment-free genotyping of",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/33871559",
+ "title": "Questions on NOTCH2NLC Repeat Expansions in Parkinson Disease.",
"type": "article-journal",
- "doi": "10.1016/j.isci.2023.107171",
+ "doi": "10.1001/jamaneurol.2021.0747",
"authors": [
- ["Hassan", "Saei"],
- ["Vincent", "Morini\u00e8re"],
- ["Laurence", "Heidet"],
- ["Olivier", "Gribouval"],
- ["Said", "Lebbah"],
- ["Frederic", "Tores"],
- ["Manon", "Mautret-Godefroy"],
- ["Bertrand", "Knebelmann"],
- ["St\u00e9phane", "Burtey"],
- ["Vincent", "Vuiblet"],
- ["Corinne", "Antignac"],
- ["Patrick", "Nitschk\u00e9"],
- ["Guillaume", "Dorval"]
+ ["Wai Yan", "Yau"],
+ ["Henry", "Houlden"],
+ ["Jana", "Vandrovcova"]
],
- "publisher": "iScience",
- "issn": "2589-0042",
- "date": "2023-06-17",
- "abstract": "The human genome comprises approximately 3% of tandem repeats with variable length (VNTR), a few of which have been linked to human rare diseases. Autosomal dominant tubulointerstitial kidney disease-",
+ "publisher": "JAMA neurology",
+ "issn": "2168-6157",
+ "date": "2021-06-01",
+ "abstract": "",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37456840"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33871559"
},
{
- "id": "pmid:37316299",
+ "id": "pmid:33871549",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/37316299",
- "title": "Hypoxia controls expression of kidney-pathogenic",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/33871549",
+ "title": "Questions on NOTCH2NLC Repeat Expansions in Parkinson Disease-Reply.",
"type": "article-journal",
- "doi": "10.26508/lsa.202302078",
+ "doi": "10.1001/jamaneurol.2021.0768",
"authors": [
- ["Stephanie", "Naas"],
- ["Ren\u00e9", "Kr\u00fcger"],
- ["Karl Xaver", "Knaup"],
- ["Julia", "Naas"],
- ["Steffen", "Grampp"],
- ["Mario", "Schiffer"],
- ["Michael", "Wiesener"],
- ["Johannes", "Sch\u00f6del"]
+ ["Dongrui", "Ma"],
+ ["Yi Jayne", "Tan"],
+ ["Eng-King", "Tan"]
],
- "publisher": "Life science alliance",
- "issn": "2575-1077",
- "date": "2023-06-14",
- "abstract": "The interplay between genetic and environmental factors influences the course of chronic kidney disease (CKD). In this context, genetic alterations in the kidney disease gene",
+ "publisher": "JAMA neurology",
+ "issn": "2168-6157",
+ "date": "2021-06-01",
+ "abstract": "",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37316299"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33871549"
},
{
- "id": "pmid:35982790",
+ "id": "pmid:33766934",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/35982790",
- "title": "Detecting tandem repeat variants in coding regions using code-adVNTR.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/33766934",
+ "title": "Genetic origin of sporadic cases and RNA toxicity in neuronal intranuclear inclusion disease.",
"type": "article-journal",
- "doi": "10.1016/j.isci.2022.104785",
+ "doi": "10.1136/jmedgenet-2020-107649",
"authors": [
- ["Jonghun", "Park"],
- ["Mehrdad", "Bakhtiari"],
- ["Bernt", "Popp"],
- ["Michael", "Wiesener"],
- ["Vineet", "Bafna"]
+ ["Jianwen", "Deng"],
+ ["Binbin", "Zhou"],
+ ["Jiaxi", "Yu"],
+ ["Xiaochen", "Han"],
+ ["Jianhui", "Fu"],
+ ["Xiaobin", "Li"],
+ ["Xufang", "Xie"],
+ ["Min", "Zhu"],
+ ["Yilei", "Zheng"],
+ ["Xueyu", "Guo"],
+ ["Pidong", "Li"],
+ ["Qingqing", "Wang"],
+ ["Jing", "Liu"],
+ ["Wei", "Zhang"],
+ ["Yun", "Yuan"],
+ ["Sheng", "Yao"],
+ ["Zhaoxia", "Wang"],
+ ["Daojun", "Hong"]
],
- "publisher": "iScience",
- "issn": "2589-0042",
- "date": "2022-07-19",
- "abstract": "The human genome contains more than one million tandem repeats (TRs), DNA sequences containing multiple approximate copies of a motif repeated contiguously. TRs account for significant genetic variation, with 50\u00a0+ diseases attributed to changes in motif number. A few diseases have been to be caused by small indels in variable number tandem repeats (VNTRs) including poly-cystic kidney disease type 1 (MCKD1) and monogenic type 1 diabetes. However, small indels in VNTRs are largely unexplored mainly due to the long and complex structure of VNTRs with multiple motifs. We developed a method, code-adVNTR, that utilizes multi-motif hidden Markov models to detect both, motif count variation and small\u00a0indels, within VNTRs. In simulated data, code-adVNTR outperformed GATK-HaplotypeCaller\u00a0in calling small indels within large VNTRs. We used code-adVNTR to characterize coding VNTRs in the 1000 genomes data identifying many population-specific variants, and to reliably call",
+ "publisher": "Journal of medical genetics",
+ "issn": "1468-6244",
+ "date": "2021-03-25",
+ "abstract": "GGC repeat expansion in",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35982790"
-},
-{
- "id": "pmid:34452200",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/34452200",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:34452200']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33766934"
},
{
- "id": "pmid:33672244",
+ "id": "pmid:33388663",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/33672244",
- "title": "Exploring Molecular Contacts of MUC1 at CIN85 Binding Interface to Address Future Drug Design Efforts.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/33388663",
+ "title": "Long-term MRI findings of adult-onset neuronal intranuclear inclusion disease.",
"type": "article-journal",
- "doi": "10.3390/ijms22042208",
+ "doi": "10.1016/j.clineuro.2020.106456",
"authors": [
- ["Maria Rita", "Gulotta"],
- ["Serena", "Vittorio"],
- ["Rosaria", "Gitto"],
- ["Ugo", "Perricone"],
- ["Laura", "De Luca"]
+ ["Kisaki", "Tachi"],
+ ["Tadayuki", "Takata"],
+ ["Kodai", "Kume"],
+ ["Jun", "Sone"],
+ ["Hideki", "Kobara"],
+ ["Kazushi", "Deguchi"],
+ ["Hideshi", "Kawakami"],
+ ["Tsutomu", "Masaki"]
],
- "publisher": "International journal of molecular sciences",
- "issn": "1422-0067",
- "date": "2021-02-23",
- "abstract": "The modulation of protein-protein interactions (PPIs) by small molecules represents a valuable strategy for pharmacological intervention in several human diseases. In this context, computer-aided drug discovery techniques offer useful resources to predict the network of interactions governing the recognition process between protein partners, thus furnishing relevant information for the design of novel PPI modulators. In this work, we focused our attention on the MUC1-CIN85 complex as a crucial PPI controlling cancer progression and metastasis. MUC1 is a transmembrane glycoprotein whose extracellular domain contains a variable number of tandem repeats (VNTRs) regions that are highly glycosylated in normal cells and under-glycosylated in cancer. The hypo-glycosylation fosters the exposure of the backbone to new interactions with other proteins, such as CIN85, that alter the intracellular signalling in tumour cells. Herein, different computational approaches were combined to investigate the molecular recognition pattern of MUC1-CIN85 PPI thus unveiling new structural information useful for the design of MUC1-CIN85 PPI inhibitors as potential anti-metastatic agents.",
+ "publisher": "Clinical neurology and neurosurgery",
+ "issn": "1872-6968",
+ "date": "2020-12-29",
+ "abstract": "",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33672244"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33388663"
},
{
- "id": "pmid:33001366",
+ "id": "pmid:33377220",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/33001366",
- "title": "TF-containing MUC1 glycopeptides fail to entice Galectin-1 recognition of tumor-associated Thomsen-Freidenreich (TF) antigen (CD176) in solution.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/33377220",
+ "title": "NOTCH2NLC Intermediate-Length Repeat Expansion and Parkinson's Disease in Patients of European Descent.",
"type": "article-journal",
- "doi": "10.1007/s10719-020-09951-x",
+ "doi": "10.1002/ana.26003",
"authors": [
- ["Forrest G", "FitzGerald"],
- ["Maria C", "Rodriguez Benavente"],
- ["Camelia", "Garcia"],
- ["Yaima", "Rivero"],
- ["YashoNandini", "Singh"],
- ["Hongjie", "Wang"],
- ["Gregg B", "Fields"],
- ["Mar\u00e9", "Cudic"]
+ ["Wai Yan", "Yau"],
+ ["Roisin", "Sullivan"],
+ ["Clarissa", "Rocca"],
+ ["Elisa", "Cali"],
+ ["Jana", "Vandrovcova"],
+ ["Nicholas W", "Wood"],
+ ["Henry", "Houlden"]
],
- "publisher": "Glycoconjugate journal",
- "issn": "1573-4986",
- "date": "2020-10-01",
- "abstract": "Aberrant Mucin-1 (MUC1) glycosylation with the Thomsen-Friedenreich (TF) tumor-associated antigen (CD176) is a hallmark of epithelial carcinoma progression and poor patient prognosis. Recognition of TF by glycan-binding proteins, such as galectins, enables the pathological repercussions of this glycan presentation, yet the underlying binding specificities of different members of the galectin family is a matter of continual investigation. While Galectin-3 (Gal-3) recognition of TF has been well-documented at both the cellular and molecular level, Galectin-1 (Gal-1) recognition of TF has only truly been alluded to in cell-based platforms. Immunohistochemical analyses have purported Gal-1 binding to TF on MUC1 at the cell surface, however binding at the molecular level was inconclusive. We hypothesize that glycan scaffold (MUC1's tandem repeat peptide sequence) and/or multivalency play a role in the binding recognition of TF antigen by Gal-1. In this study we have developed a method for large-scale expression of Gal-1 and its histidine-tagged analog for use in binding studies by isothermal titration calorimetry (ITC) and development of an analytical method based on AlphaScreen technology to screen for Gal-1 inhibitors. Surprisingly, neither glycan scaffold or multivalent presentation of TF antigen on the scaffold was able to entice Gal-1 recognition to the level of affinity expected for functional significance. Future evaluations of the Gal-1/TF binding interaction in order to draw connections between immunohistochemical data and analytical measurements are warranted.",
+ "publisher": "Annals of neurology",
+ "issn": "1531-8249",
+ "date": "2021-01-11",
+ "abstract": "",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33001366"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33377220"
},
{
- "id": "pmid:30593830",
+ "id": "pmid:33377207",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/30593830",
- "title": "Targeting cell-bound MUC1 on myelomonocytic, monocytic leukemias and phenotypically defined leukemic stem cells with anti-SEA module antibodies.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/33377207",
+ "title": "Reply to \"NOTCH2NLC Intermediate-Length Repeat Expansions Are Associated with Parkinson Disease\".",
"type": "article-journal",
- "doi": "10.1016/j.exphem.2018.12.002",
+ "doi": "10.1002/ana.26005",
"authors": [
- ["Thierry", "Guillaume"],
- ["Virginie", "Dehame"],
- ["Patrice", "Chevallier"],
- ["Pierre", "Peterlin"],
- ["Alice", "Garnier"],
- ["Marc", "Gr\u00e9goire"],
- ["Edward", "Pichinuk"],
- ["Daniel B", "Rubinstein"],
- ["Daniel H", "Wreschner"]
+ ["Chang-He", "Shi"],
+ ["Yu", "Fan"],
+ ["Yu-Ming", "Xu"]
],
- "publisher": "Experimental hematology",
- "issn": "1873-2399",
- "date": "2018-12-26",
- "abstract": "Cell surface molecules aberrantly expressed or overexpressed by myeloid leukemic cells represent potential disease-specific therapeutic targets for antibodies. MUC1 is a polymorphic glycoprotein, the cleavage of which yields two unequal chains: a large extracellular \u03b1 subunit containing a tandem repeat array bound in a strong noncovalent interaction to a smaller \u03b2 subunit containing the transmembrane and cytoplasmic domains. Because the \u03b1-chain can be released from the cell-bound domains of MUC1, agents directed against the \u03b1-chain will not effectively target MUC1",
+ "publisher": "Annals of neurology",
+ "issn": "1531-8249",
+ "date": "2021-01-11",
+ "abstract": "",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30593830"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33377207"
},
{
- "id": "pmid:29520014",
+ "id": "pmid:33146671",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/29520014",
- "title": "Single molecule real time sequencing in ADTKD-MUC1 allows complete assembly of the VNTR and exact positioning of causative mutations.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/33146671",
+ "title": "Assessing the NOTCH2NLC GGC expansion in European patients with essential tremor.",
"type": "article-journal",
- "doi": "10.1038/s41598-018-22428-0",
+ "doi": "10.1093/brain/awaa291",
"authors": [
- ["Andrea", "Wenzel"],
- ["Janine", "Altmueller"],
- ["Arif B", "Ekici"],
- ["Bernt", "Popp"],
- ["Kurt", "Stueber"],
- ["Holger", "Thiele"],
- ["Alois", "Pannes"],
- ["Simon", "Staubach"],
- ["Eduardo", "Salido"],
- ["Peter", "Nuernberg"],
- ["Richard", "Reinhardt"],
- ["Andr\u00e9", "Reis"],
- ["Patrick", "Rump"],
- ["Franz-Georg", "Hanisch"],
- ["Matthias T F", "Wolf"],
- ["Michael", "Wiesener"],
- ["Bruno", "Huettel"],
- ["Bodo B", "Beck"]
+ ["Calwing", "Liao"],
+ ["Fulya", "Ak\u00e7imen"],
+ ["Monica", "Diez-Fairen"],
+ ["Gabrielle", "Houle"],
+ ["Jay P", "Ross"],
+ ["Zoe", "Schmilovich"],
+ ["Dan", "Spiegelman"],
+ ["Veikko", "Vuokila"],
+ ["H\u00e9l\u00e8ne", "Catoire"],
+ ["Inge A", "Meijer"],
+ ["Pau", "Pastor"],
+ ["Alex", "Rajput"],
+ ["Patrick A", "Dion"],
+ ["Guy A", "Rouleau"]
],
- "publisher": "Scientific reports",
- "issn": "2045-2322",
- "date": "2018-03-08",
- "abstract": "Recently, the Mucin-1 (MUC1) gene has been identified as a causal gene of autosomal dominant tubulointerstitial kidney disease (ADTKD). Most causative mutations are buried within a GC-rich 60 basepair variable number of tandem repeat (VNTR), which escapes identification by massive parallel sequencing methods due to the complexity of the VNTR. We established long read single molecule real time sequencing (SMRT) targeted to the MUC1-VNTR as an alternative strategy to the snapshot assay. Our approach allows complete VNTR assembly, thereby enabling the detection of all variants residing within the VNTR and simultaneous determination of VNTR length. We present high resolution data on the VNTR architecture for a cohort of snapshot positive (n\u2009=\u20099) and negative (n\u2009=\u20097) ADTKD families. By SMRT sequencing we could confirm the diagnosis in all previously tested cases, reconstruct both VNTR alleles and determine the exact position of the causative variant in eight of nine families. This study demonstrates that precise positioning of the causative mutation(s) and identification of other coding and noncoding sequence variants in ADTKD-MUC1 is feasible. SMRT sequencing could provide a powerful tool to uncover potential factors encoded within the VNTR that associate with intra- and interfamilial phenotype variability of MUC1 related kidney disease.",
+ "publisher": "Brain : a journal of neurology",
+ "issn": "1460-2156",
+ "date": "2020-12-05",
+ "abstract": "",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29520014"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33146671"
},
{
- "id": "pmid:29328069",
+ "id": "pmid:33016348",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/29328069",
- "title": "Inhibition of MUC1 biosynthesis via threonyl-tRNA synthetase suppresses pancreatic cancer cell migration.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/33016348",
+ "title": "NOTCH2NLC Intermediate-Length Repeat Expansions Are Associated with Parkinson Disease.",
"type": "article-journal",
- "doi": "10.1038/emm.2017.231",
+ "doi": "10.1002/ana.25925",
"authors": [
- ["Seung Jae", "Jeong"],
- ["Jong Hyun", "Kim"],
- ["Beom Jin", "Lim"],
- ["Ina", "Yoon"],
- ["Ji-Ae", "Song"],
- ["Hee-Sun", "Moon"],
- ["Doyeun", "Kim"],
- ["Dong Ki", "Lee"],
- ["Sunghoon", "Kim"]
- ],
- "publisher": "Experimental & molecular medicine",
- "issn": "2092-6413",
- "date": "2018-01-12",
- "abstract": "Mucin1 (MUC1), a heterodimeric oncoprotein, containing tandem repeat structures with a high proportion of threonine, is aberrantly overexpressed in many human cancers including pancreatic cancer. Since the overall survival rate of pancreatic cancer patients has remained low for several decades, novel therapeutic approaches are highly needed. Intestinal mucin has been known to be affected by dietary threonine supply since de novo synthesis of mucin proteins is sensitive to luminal threonine concentration. However, it is unknown whether biosynthesis of MUC1 is regulated by threonine in human cancers. In this study, data provided suggests that threonine starvation reduces the level of MUC1 and inhibits the migration of MUC1-expressing pancreatic cancer cells. Interestingly, knockdown of threonyl-tRNA synthetase (TRS), an enzyme that catalyzes the ligation of threonine to its cognate tRNA, also suppresses MUC1 levels but not mRNA levels. The inhibitors of TRS decrease the level of MUC1 protein and prohibit the migration of MUC1-expressing pancreatic cancer cells. In addition, a positive correlation between TRS and MUC1 levels is observed in human pancreatic cancer cells. Concurrent with these results, the bioinformatics data indicate that co-expression of both TRS and MUC1 is correlated with the poor survival of pancreatic cancer patients. Taken together, these findings suggest a role for TRS in controlling MUC1-mediated cancer cell migration and provide insight into targeting TRS as a novel therapeutic approach to pancreatic cancer treatment.",
+ ["Chang-He", "Shi"],
+ ["Yu", "Fan"],
+ ["Jing", "Yang"],
+ ["Yan-Peng", "Yuan"],
+ ["Si", "Shen"],
+ ["Fen", "Liu"],
+ ["Cheng-Yuan", "Mao"],
+ ["Han", "Liu"],
+ ["Shuo", "Zhang"],
+ ["Zheng-Wei", "Hu"],
+ ["Li-Yuan", "Fan"],
+ ["Meng-Jie", "Li"],
+ ["Shi-Heng", "Fan"],
+ ["Xiao-Jing", "Liu"],
+ ["Yu-Ming", "Xu"]
+ ],
+ "publisher": "Annals of neurology",
+ "issn": "1531-8249",
+ "date": "2020-10-19",
+ "abstract": "NOTCH2NLC GGC repeat expansions were recently identified in neuronal intranuclear inclusion disease (NIID); however, it remains unclear whether they occur in other neurodegenerative disorders. This study aimed to investigate the role of intermediate-length NOTCH2NLC GGC repeat expansions in Parkinson disease (PD). We screened for GGC repeat expansions in a cohort of 1,011 PD patients and identified 11 patients with intermediate-length repeat expansions ranging from 41 to 52 repeats, with no repeat expansions in 1,134 controls. Skin biopsy revealed phospho-alpha-synuclein deposition, confirming the PD diagnosis in 2 patients harboring intermediate-length repeat expansions instead of NIID or essential tremor. Fibroblasts from PD patients harboring intermediate-length repeat expansions revealed NOTCH2NLC upregulation and autophagic dysfunction. Our results suggest that intermediate-length repeat expansions in NOTCH2NLC are potentially associated with PD. ANN NEUROL 2021;89:182-187.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29328069"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33016348"
},
{
- "id": "pmid:28581490",
+ "id": "pmid:32817896",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/28581490",
- "title": "Assessment of tumor characteristics based on glycoform analysis of membrane-tethered MUC1.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/32817896",
+ "title": "A case of neuronal intranuclear inclusion disease with recurrent vomiting and without apparent DWI abnormality for the first seven years.",
"type": "article-journal",
- "doi": "10.1038/labinvest.2017.53",
+ "doi": "10.1016/j.heliyon.2020.e04675",
"authors": [
- ["Atsushi", "Matsuda"],
- ["Michiyo", "Higashi"],
- ["Tomomi", "Nakagawa"],
- ["Seiya", "Yokoyama"],
- ["Atsushi", "Kuno"],
- ["Suguru", "Yonezawa"],
- ["Hisashi", "Narimatsu"]
+ ["Shun", "Okamura"],
+ ["Makoto", "Takahashi"],
+ ["Keisuke", "Abe"],
+ ["Akira", "Inaba"],
+ ["Jun", "Sone"],
+ ["Satoshi", "Orimo"]
],
- "publisher": "Laboratory investigation; a journal of technical methods and pathology",
- "issn": "1530-0307",
- "date": "2017-06-05",
- "abstract": "Clinical tissue specimens are useful for pathological diagnosis, which is, in some cases, supported by visualization of biomolecule localization. In general, diagnostic specificity in molecular pathology is increased by the acquisition of a probe to distinguish the modification of isomers. Although glycosylation is one of the candidate modifications in a protein, comparative glycan analysis of disease-associated proteins derived from a single tissue section is still challenging because of the lack of analytical sensitivity. Here we demonstrate a possible method for differential glycoform analysis of an endogenous tumor-associated glycoprotein MUC1 by an antibody-overlay lectin microarray. Tissue sections (5\u2009\u03bcm thick) of patients with cholangiocarcinoma (CCA; n=21) and pancreatic ductal adenocarcinoma (PDAC; n=50) were stained with an anti-MUC1 antibody MY.1E12 that was established as a monoclonal antibody recognizing an MUC1 glycosylation isoform with a sialyl-core 1 structure (NeuAc\u03b12-3galactosyl \u03b21-3-N-acetylgalactosamine). MY.1E12-positive tissue areas (2.5\u2009mm",
+ "publisher": "Heliyon",
+ "issn": "2405-8440",
+ "date": "2020-08-11",
+ "abstract": "Neuronal intranuclear inclusion disease (NIID) is a rare, neurodegenerative disorder characterized by the presence of eosinophilic hyaline intranuclear inclusions, which are ubiquitin-positive and p62-positive, in neuronal and somatic cells; this can be observed on skin biopsy. Although patients with NIID present with a variety of symptoms that often make the diagnosis difficult, characteristic high-signal intensity of the corticomedullary junction on diffusion-weighted imaging (DWI) often provides a clue to the diagnosis of NIID. We present a case of NIID in a 57-year-old woman who only had recurrent vomiting for four years, which is uncommon as the presenting symptom; moreover, DWI showed no apparent abnormality until a slightly abnormal intensity lesion appeared at the right frontal corticomedullary junction seven years after the first episode of recurrent vomiting. Skin biopsies revealed multiple p62-positive nuclear inclusions, and genetic test showed GGC repeat expansion in",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28581490"
-},
-{
- "id": "pmid:28407289",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/28407289",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:28407289']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32817896"
},
{
- "id": "pmid:27957769",
+ "id": "pmid:32777174",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/27957769",
- "title": "Microarray Analysis of Antibodies Induced with Synthetic Antitumor Vaccines: Specificity against Diverse Mucin Core Structures.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/32777174",
+ "title": "Neuronal intranuclear inclusion disease is genetically heterogeneous.",
"type": "article-journal",
- "doi": "10.1002/chem.201603921",
+ "doi": "10.1002/acn3.51151",
"authors": [
- ["Christian", "Pett"],
- ["Hui", "Cai"],
- ["Jia", "Liu"],
- ["Bj\u00f6rn", "Palitzsch"],
- ["Manuel", "Schorlemer"],
- ["Sebastian", "Hartmann"],
- ["Natascha", "Stergiou"],
- ["Mengji", "Lu"],
- ["Horst", "Kunz"],
- ["Edgar", "Schmitt"],
- ["Ulrika", "Westerlind"]
+ ["Zhongbo", "Chen"],
+ ["Wai", "Yan Yau"],
+ ["Zane", "Jaunmuktane"],
+ ["Arianna", "Tucci"],
+ ["Prasanth", "Sivakumar"],
+ ["Sarah A", "Gagliano Taliun"],
+ ["Chris", "Turner"],
+ ["Stephanie", "Efthymiou"],
+ ["Kristina", "Ib\u00e1\u00f1ez"],
+ ["Roisin", "Sullivan"],
+ ["Farah", "Bibi"],
+ ["Alkyoni", "Athanasiou-Fragkouli"],
+ ["Thomas", "Bourinaris"],
+ ["David", "Zhang"],
+ ["Tamas", "Revesz"],
+ ["Tammaryn", "Lashley"],
+ ["Michael", "DeTure"],
+ ["Dennis W", "Dickson"],
+ ["Keith A", "Josephs"],
+ ["Ellen", "Gelpi"],
+ ["Gabor G", "Kovacs"],
+ ["Glenda", "Halliday"],
+ ["Dominic B", "Rowe"],
+ ["Ian", "Blair"],
+ ["Pentti J", "Tienari"],
+ ["Anu", "Suomalainen"],
+ ["Nick C", "Fox"],
+ ["Nicholas W", "Wood"],
+ ["Andrew J", "Lees"],
+ ["Matti J", "Haltia"],
+ ["John", "Hardy"],
+ ["Mina", "Ryten"],
+ ["Jana", "Vandrovcova"],
+ ["Henry", "Houlden"]
],
- "publisher": "Chemistry (Weinheim an der Bergstrasse, Germany)",
- "issn": "1521-3765",
- "date": "2017-01-23",
- "abstract": "Glycoprotein research is pivotal for vaccine development and biomarker discovery. Many successful methodologies for reliably increasing the antigenicity toward tumor-associated glycopeptide structures have been reported. Deeper insights into the quality and specificity of the raised polyclonal, humoral reactions are often not addressed, despite the fact that an immunological memory, which produces antibodies with cross-reactivity to epitopes exposed on healthy cells, may cause autoimmune diseases. In the current work, three MUC1 antitumor vaccine candidates conjugated with different immune stimulants are evaluated immunologically. For assessment of the influence of the immune stimulant on antibody recognition, a comprehensive library of mucin 1 glycopeptides (>100 entries) is synthesized and employed in antibody microarray profiling; these range from small tumor-associated glycans (T",
+ "publisher": "Annals of clinical and translational neurology",
+ "issn": "2328-9503",
+ "date": "2020-08-10",
+ "abstract": "Neuronal intranuclear inclusion disease (NIID) is a clinically heterogeneous neurodegenerative condition characterized by pathological intranuclear eosinophilic inclusions. A CGG repeat expansion in NOTCH2NLC was recently identified to be associated with NIID in patients of Japanese descent. We screened pathologically confirmed European NIID, cases of neurodegenerative disease with intranuclear inclusions and applied in silico-based screening using whole-genome sequencing data from 20\u00a0536 participants in the 100\u00a0000 Genomes Project. We identified a single European case harbouring the pathogenic repeat expansion with a distinct haplotype structure. Thus, we propose new diagnostic criteria as European NIID represents a distinct disease entity from East Asian cases.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27957769"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32777174"
},
{
- "id": "pmid:27157321",
+ "id": "pmid:32768149",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/27157321",
- "title": "Development and Validation of a Mass Spectrometry-Based Assay for the Molecular Diagnosis of Mucin-1 Kidney Disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/32768149",
+ "title": "No genetic evidence for the involvement of GGC repeat expansions of the NOTCH2NLC gene in Chinese patients with multiple system atrophy.",
"type": "article-journal",
- "doi": "10.1016/j.jmoldx.2016.03.003",
+ "doi": "10.1016/j.neurobiolaging.2020.07.008",
"authors": [
- ["Brendan", "Blumenstiel"],
- ["Matthew", "DeFelice"],
- ["Ozge", "Birsoy"],
- ["Anthony J", "Bleyer"],
- ["Stanislav", "Kmoch"],
- ["Todd A", "Carter"],
- ["Andreas", "Gnirke"],
- ["Kendrah", "Kidd"],
- ["Heidi L", "Rehm"],
- ["Lucienne", "Ronco"],
- ["Eric S", "Lander"],
- ["Stacey", "Gabriel"],
- ["Niall J", "Lennon"]
+ ["Keqin", "Xu"],
+ ["Linlin", "Wan"],
+ ["Zhao", "Chen"],
+ ["Chunrong", "Wang"],
+ ["Huirong", "Peng"],
+ ["Xuan", "Hou"],
+ ["Yuting", "Shi"],
+ ["Rong", "Qiu"],
+ ["Beisha", "Tang"],
+ ["Hong", "Jiang"]
],
- "publisher": "The Journal of molecular diagnostics : JMD",
- "issn": "1943-7811",
- "date": "2016-05-05",
- "abstract": "Mucin-1 kidney disease, previously described as medullary cystic kidney disease type 1 (MCKD1, OMIM 174000), is an autosomal dominant tubulointerstitial kidney disease recently shown to be caused by a single-base insertion within the variable number tandem repeat region of the MUC1 gene. Because of variable age of disease onset and often subtle signs and symptoms, clinical diagnosis of mucin-1 kidney disease and differentiation from other forms of hereditary kidney disease have been difficult. The causal insertion resides in a variable number tandem repeat region with high GC content, which has made detection by standard next-generation sequencing impossible to date. The inherently difficult nature of this mutation required an alternative method for routine detection and clinical diagnosis of the disease. We therefore developed and validated a mass spectrometry-based probe extension assay with a series of internal controls to detect the insertion event using 24 previously characterized positive samples from patients with mucin-1 kidney disease and 24 control samples known to be wild type for the variant. Validation results indicate an accurate and reliable test for clinically establishing the molecular diagnosis of mucin-1 kidney disease with 100% sensitivity and specificity across 275 tests called.",
+ "publisher": "Neurobiology of aging",
+ "issn": "1558-1497",
+ "date": "2020-07-15",
+ "abstract": "Recent studies have identified an expanded GGC repeat in the 5' untranslated region of the NOTCH2NLC gene as a possible pathogenic genetic cause of neuronal intranuclear inclusion disease. Converging evidence verifying the presence of the same GGC repeat expansion in patients with Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases has also received increased attention. Inspired by some of the clinical similarities between neuronal intranuclear inclusion disease and multiple system atrophy (MSA), we used repeat-primed PCR to explore the occurrence of GGC repeats in 328 patients with MSA in mainland China. Our result failed to detect any GGC repeat expansion in these patients with MSA, indicating that the NOTCH2NLC gene may not be involved in the pathogenesis of MSA.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27157321"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32768149"
},
{
- "id": "pmid:26943180",
+ "id": "pmid:32495371",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26943180",
- "title": "Testing for the cytosine insertion in the VNTR of the MUC1 gene in a cohort of Italian patients with autosomal dominant tubulointerstitial kidney disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/32495371",
+ "title": "NOTCH2NLC GGC Repeat Expansions Are Associated with Sporadic Essential Tremor: Variable Disease Expressivity on Long-Term Follow-up.",
"type": "article-journal",
- "doi": "10.1007/s40620-016-0282-9",
+ "doi": "10.1002/ana.25803",
"authors": [
- ["Claudio", "Musetti"],
- ["Deepak", "Babu"],
- ["Ileana", "Fusco"],
- ["Simona", "Mellone"],
- ["Andrea", "Zonta"],
- ["Marco", "Quaglia"],
- ["Vincenzo", "Cantaluppi"],
- ["Piero", "Stratta"],
- ["Mara", "Giordano"]
+ ["Adeline S L", "Ng"],
+ ["Weng Khong", "Lim"],
+ ["Zheyu", "Xu"],
+ ["Helen L", "Ong"],
+ ["Yi Jayne", "Tan"],
+ ["Wei Ying", "Sim"],
+ ["Ebonne Y L", "Ng"],
+ ["Jing Xian", "Teo"],
+ ["Jia Nee", "Foo"],
+ ["Tchoyoson C C", "Lim"],
+ ["Wai-Yung", "Yu"],
+ ["Ling-Ling", "Chan"],
+ ["Hwei-Yee", "Lee"],
+ ["Zhiyong", "Chen"],
+ ["Ee-Wei", "Lim"],
+ ["Simon K S", "Ting"],
+ ["Kumar M", "Prakash"],
+ ["Louis C S", "Tan"],
+ ["Zhao", "Yi"],
+ ["Eng-King", "Tan"]
],
- "publisher": "Journal of nephrology",
- "issn": "1724-6059",
- "date": "2016-03-04",
- "abstract": "Medullary cystic kidney disease type 1 (MCKD1; OMIM #174000) is a familial progressive tubule-interstitial nephropathy belonging to the recently defined group of autosomal dominant tubulointerstitial kidney diseases (ADTKD).",
+ "publisher": "Annals of neurology",
+ "issn": "1531-8249",
+ "date": "2020-07-16",
+ "abstract": "We screened 662 subjects comprising 462 essential tremor (ET) subjects (285 sporadic, 125 with family history, and 52 probands from well-characterized ET pedigrees) and 200 controls and identified pathogenic NOTCH2NLC GGC repeat expansions in 4 sporadic ET patients. Two patients were followed up for >1 decade; one with 90 repeats remained an ET phenotype that did not evolve after 40\u2009years, whereas another patient with 107 repeats developed motor symptoms and cognitive impairment after 8 to 10\u2009years. Neuroimaging in this patient revealed severe leukoencephalopathy; diffusion-weighted imaging hyperintensity in the corticomedullary junction and skin biopsy revealed intranuclear inclusions suggestive of intranuclear inclusion body disease (NIID). No GGC repeats of >60\u2009units were detected in familial ET cases and controls, although 4 ET patients carried 47 to 53 \"intermediate\" repeats. NOTCH2NLC GGC repeat expansions can be associated with sporadic ET. Carriers presenting with a pure ET phenotype may or may not convert to NIID up to 4 decades after initial tremor onset. ANN NEUROL 2020;88:614-618.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26943180"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32495371"
},
{
- "id": "pmid:26838233",
+ "id": "pmid:32449905",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26838233",
- "title": "Usefulness of Salivary and Serum Auto-antibodies Against Tumor Biomarkers HER2 and MUC1 in Breast Cancer Screening.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/32449905",
+ "title": "Essential tremor as the early symptom of NOTCH2NLC gene-related repeat expansion disorder.",
"type": "article-journal",
- "doi": "10.7314/apjcp.2016.17.1.335",
+ "doi": "10.1093/brain/awaa142",
"authors": [
- ["Fatna", "Laidi"],
- ["Amal", "Bouziane"],
- ["Abdelhamid", "Errachid"],
- ["Fatima", "Zaoui"]
+ ["Hao", "Chen"],
+ ["Likui", "Lu"],
+ ["Bin", "Wang"],
+ ["Xiaodong", "Hua"],
+ ["Bo", "Wan"],
+ ["Miao", "Sun"],
+ ["Xingshun", "Xu"]
],
- "publisher": "Asian Pacific journal of cancer prevention : APJCP",
- "issn": "2476-762X",
- "date": "2016-01-01",
- "abstract": "The aim of this work was to investigate if serum and salivary auto-antibodies, isotypes IgG and IgM, against HER2 and MUC1 tandem repeat fragments could play a role in breast cancer screening.",
+ "publisher": "Brain : a journal of neurology",
+ "issn": "1460-2156",
+ "date": "2020-07-01",
+ "abstract": "",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26838233"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32449905"
},
{
- "id": "pmid:25753030",
+ "id": "pmid:32268889",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25753030",
- "title": "In healthy volunteers, immunohistochemistry supports squamous to columnar metaplasia as mechanism of expansion of cardia, aggravated by central obesity.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/32268889",
+ "title": "Multiple reversible encephalitic attacks: a rare manifestation of neuronal intranuclear inclusion disease.",
"type": "article-journal",
- "doi": "10.1136/gutjnl-2014-308914",
+ "doi": "10.1186/s12883-020-01712-5",
"authors": [
- ["Mohammad H", "Derakhshan"],
- ["Elaine V", "Robertson"],
- ["Yeong", "Yeh Lee"],
- ["Tim", "Harvey"],
- ["Rod K", "Ferrier"],
- ["Angela A", "Wirz"],
- ["Clare", "Orange"],
- ["Stuart A", "Ballantyne"],
- ["Scott L", "Hanvey"],
- ["James J", "Going"],
- ["Kenneth E L", "McColl"]
+ ["Mingming", "Li"],
+ ["Kai", "Li"],
+ ["Xin", "Li"],
+ ["Yun", "Tian"],
+ ["Lu", "Shen"],
+ ["Guode", "Wu"],
+ ["Zaiqiang", "Zhang"],
+ ["Weian", "Chen"]
],
- "publisher": "Gut",
- "issn": "1468-3288",
- "date": "2015-03-09",
- "abstract": "Recently, we showed that the length of cardiac mucosa in healthy volunteers correlated with age and obesity. We have now examined the immunohistological characteristics of this expanded cardia to determine whether it may be due to columnar metaplasia of the distal oesophagus.",
+ "publisher": "BMC neurology",
+ "issn": "1471-2377",
+ "date": "2020-04-08",
+ "abstract": "Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative condition characterized by the loss of neurons and the presence of eosinophilic nuclear inclusions in the central and peripheral nervous system, skin and visceral organs. In this paper, we present a case of NIID with recurrent encephalitic attacks that remained stable and nonprogressive for seven years; no such case has previously been reported.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25753030"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32268889"
},
{
- "id": "pmid:24718884",
+ "id": "pmid:31819945",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/24718884",
- "title": "Specific MUC1 splice variants are correlated with tumor progression in esophageal cancer.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/31819945",
+ "title": "Expansion of GGC repeat in the human-specific NOTCH2NLC gene is associated with essential tremor.",
"type": "article-journal",
- "doi": "10.1007/s00268-014-2523-1",
+ "doi": "10.1093/brain/awz372",
"authors": [
- ["Kolsoum Rezaie", "Kahkhaie"],
- ["Omeed", "Moaven"],
- ["Mohammad Reza", "Abbaszadegan"],
- ["Mehdi", "Montazer"],
- ["Mehran", "Gholamin"]
+ ["Qi-Ying", "Sun"],
+ ["Qian", "Xu"],
+ ["Yun", "Tian"],
+ ["Zheng-Mao", "Hu"],
+ ["Li-Xia", "Qin"],
+ ["Jin-Xia", "Yang"],
+ ["Wen", "Huang"],
+ ["Jin", "Xue"],
+ ["Jin-Chen", "Li"],
+ ["Sheng", "Zeng"],
+ ["Ying", "Wang"],
+ ["Hao-Xuan", "Min"],
+ ["Xiao-Yu", "Chen"],
+ ["Jun-Pu", "Wang"],
+ ["Bin", "Xie"],
+ ["Fan", "Liang"],
+ ["Hai-Nan", "Zhang"],
+ ["Chun-Yu", "Wang"],
+ ["Li-Fang", "Lei"],
+ ["Xin-Xiang", "Yan"],
+ ["Hong-Wei", "Xu"],
+ ["Ran-Hui", "Duan"],
+ ["Kun", "Xia"],
+ ["Jing-Yu", "Liu"],
+ ["Hong", "Jiang"],
+ ["Lu", "Shen"],
+ ["Ji-Feng", "Guo"],
+ ["Bei-Sha", "Tang"]
],
- "publisher": "World journal of surgery",
- "issn": "1432-2323",
- "date": "2014-08-01",
- "abstract": "Mucin 1 (MUC1) is a complex glycoprotein expressed on the apical surface of normal glandular epithelial cells. It plays a role in a number of biologic processes, and its overexpression is associated with various malignancies. A growing body of literature suggests that MUC1 is a potential diagnostic and therapeutic marker. Increasing numbers of variants are being identified for the MUC1 gene, but their role in carcinogenesis is unclear. Alternative splicing and a specific region on a variable number of tandem repeats are characteristic features of MUC1. However, the underlying mechanisms, overall prevalence, and the function of various MUC1 isoforms are not well characterized.",
+ "publisher": "Brain : a journal of neurology",
+ "issn": "1460-2156",
+ "date": "2020-01-01",
+ "abstract": "Essential tremor is one of the most common movement disorders. Despite its high prevalence and heritability, the genetic aetiology of essential tremor remains elusive. Up to now, only a few genes/loci have been identified, but these genes have not been replicated in other essential tremor families or cohorts. Here we report a genetic study in a cohort of 197 Chinese pedigrees clinically diagnosed with essential tremor. Using a comprehensive strategy combining linkage analysis, whole-exome sequencing, long-read whole-genome sequencing, repeat-primed polymerase chain reaction and GC-rich polymerase chain reaction, we identified an abnormal GGC repeat expansion in the 5' region of the NOTCH2NLC gene that co-segregated with disease in 11 essential tremor families (5.58%) from our cohort. Clinically, probands that had an abnormal GGC repeat expansion were found to have more severe tremor phenotypes, lower activities of daily living ability. Obvious genetic anticipation was also detected in these 11 essential tremor-positive families. These results indicate that abnormal GGC repeat expansion in the 5' region of NOTCH2NLC gene is associated with essential tremor, and provide strong evidence that essential tremor is a family of diseases with high clinical and genetic heterogeneities.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24718884"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31819945"
},
{
- "id": "pmid:24509297",
+ "id": "pmid:31433517",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/24509297",
- "title": "Variable clinical presentation of an MUC1 mutation causing medullary cystic kidney disease type 1.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/31433517",
+ "title": "GGC Repeat Expansion of NOTCH2NLC in Adult Patients with Leukoencephalopathy.",
"type": "article-journal",
- "doi": "10.2215/cjn.06380613",
+ "doi": "10.1002/ana.25586",
"authors": [
- ["Anthony J", "Bleyer"],
- ["Stanislav", "Kmoch"],
- ["Corinne", "Antignac"],
- ["Vicki", "Robins"],
- ["Kendrah", "Kidd"],
- ["John R", "Kelsoe"],
- ["Gerald", "Hladik"],
- ["Philip", "Klemmer"],
- ["Stephen J", "Knohl"],
- ["Steven J", "Scheinman"],
- ["Nam", "Vo"],
- ["Ann", "Santi"],
- ["Alese", "Harris"],
- ["Omar", "Canaday"],
- ["Nelson", "Weller"],
- ["Peter J", "Hulick"],
- ["Kristen", "Vogel"],
- ["Frederick F", "Rahbari-Oskoui"],
- ["Jennifer", "Tuazon"],
- ["Constantinos", "Deltas"],
- ["Douglas", "Somers"],
- ["Andre", "Megarbane"],
- ["Paul L", "Kimmel"],
- ["C John", "Sperati"],
- ["Avi", "Orr-Urtreger"],
- ["Shay", "Ben-Shachar"],
- ["David A", "Waugh"],
- ["Stella", "McGinn"],
- ["Anthony J", "Bleyer"],
- ["Katerina", "Hodanov\u00e1"],
- ["Petr", "Vylet'al"],
- ["Martina", "\u017divn\u00e1"],
- ["Thomas C", "Hart"],
- ["P Suzanne", "Hart"]
+ ["Masaki", "Okubo"],
+ ["Hiroshi", "Doi"],
+ ["Ryoko", "Fukai"],
+ ["Atsushi", "Fujita"],
+ ["Satomi", "Mitsuhashi"],
+ ["Shunta", "Hashiguchi"],
+ ["Hitaru", "Kishida"],
+ ["Naohisa", "Ueda"],
+ ["Keisuke", "Morihara"],
+ ["Akihiro", "Ogasawara"],
+ ["Yuko", "Kawamoto"],
+ ["Tatsuya", "Takahashi"],
+ ["Keita", "Takahashi"],
+ ["Haruko", "Nakamura"],
+ ["Misako", "Kunii"],
+ ["Mikiko", "Tada"],
+ ["Atsuko", "Katsumoto"],
+ ["Hiromi", "Fukuda"],
+ ["Takeshi", "Mizuguchi"],
+ ["Satoko", "Miyatake"],
+ ["Noriko", "Miyake"],
+ ["Junichiro", "Suzuki"],
+ ["Yasuhiro", "Ito"],
+ ["Jun", "Sone"],
+ ["Gen", "Sobue"],
+ ["Hideyuki", "Takeuchi"],
+ ["Naomichi", "Matsumoto"],
+ ["Fumiaki", "Tanaka"]
],
- "publisher": "Clinical journal of the American Society of Nephrology : CJASN",
- "issn": "1555-905X",
- "date": "2014-02-07",
- "abstract": "The genetic cause of medullary cystic kidney disease type 1 was recently identified as a cytosine insertion in the variable number of tandem repeat region of MUC1 encoding mucoprotein-1 (MUC1), a protein that is present in skin, breast, and lung tissue, the gastrointestinal tract, and the distal tubules of the kidney. The purpose of this investigation was to analyze the clinical characteristics of families and individuals with this mutation.",
+ "publisher": "Annals of neurology",
+ "issn": "1531-8249",
+ "date": "2019-10-22",
+ "abstract": "Leukoencephalopathies comprise a broad spectrum of disorders, but the genetic background of adult leukoencephalopathies has rarely been assessed. In this study, we analyzed 101 Japanese patients with genetically unresolved adult leukoencephalopathy using whole-exome sequencing and repeat-primed polymerase chain reaction for detecting GGC expansion in NOTCH2NLC. NOTCH2NLC was recently identified as the cause of neuronal intranuclear inclusion disease. We found 12 patients with GGC expansion in NOTCH2NLC as the most frequent cause of adult leukoencephalopathy followed by NOTCH3 variants in our cohort. Furthermore, we found 1 case with de novo GGC expansion, which might explain the underlying pathogenesis of sporadic cases. ANN NEUROL 2019;86:962-968.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24509297"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31433517"
},
{
- "id": "pmid:23778023",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/23778023",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:23778023']' timed out after 3 seconds"
+ "id": "pmid:40594369",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/40594369",
+ "title": "Feasibility of long-read sequencing to identify molecular alterations in an Indonesian cohort of locally advanced to advanced nasopharyngeal cancer.",
+ "type": "article-journal",
+ "doi": "10.1038/s41598-025-06096-5",
+ "authors": [
+ ["", "Handoko"],
+ ["Marlinda", "Adham"],
+ ["Lisnawati", "Rachmadi"],
+ ["Demak Lumban", "Tobing"],
+ ["", "Asmarinah"],
+ ["", "Fadilah"],
+ ["Wei", "Dai"],
+ ["Anne Wing Mui", "Lee"],
+ ["Soehartati A", "Gondhowiardjo"]
+ ],
+ "publisher": "Scientific reports",
+ "issn": "2045-2322",
+ "date": "2025-07-01",
+ "abstract": "Nasopharyngeal carcinoma (NPC) is prevalent in Southeast Asia, particularly in Indonesia. Despite advances in treatment, patients with advanced NPC face poor outcomes. Examining the NPC mutational landscape is crucial for understanding its biology and enable potential new therapeutic strategy. To characterize the landscape of single nucleotide variants (SNVs), structural variants (SVs), copy number variations (CNVs), and short tandem repeats (STRs) in locally advanced to advanced NPC within an Indonesian cohort using long-read sequencing. Six fresh-frozen nasopharyngeal biopsy samples were collected from the NPC biobank. DNA was extracted and sequenced using Oxford Nanopore's Promethion 2 Solo long-read sequencer. Structural and small variants were identified and annotated. The SNVs, SVs, and CNVs were categorized based on predicted effects, and key findings were validated using external RNA-seq data. Copy number loss genes were checked against the Tumour Suppressor Gene database (TSGene v2.0). Genetic findings were correlated with patient clinical histories. Approximately 4.4 to 5.1\u00a0million SNVs were identified per sample, with 0.023% categorized as high consequence. Notable tumour suppressor genes, such as LIMD1 and CNDP2, were frequently mutated. Around 30,000 to 41,599 SVs were detected per sample. High-consequence tumour suppressor gene SVs were identified in EPHA3, CASP8, DMBT1, ZFHX3, and IRF5 gene. Common copy number tumour suppressor gene loss observed in RNH1, H19, CDKN1C, and others, suggesting their role in NPC carcinogenesis. Copy number gains were found in potential oncogenes such as Y RNA, LTO1, and FADD. Pathogenic short tandem repeats (STRs) in PABPN1 and RFC1 were identified in three samples, presenting a novel association with NPC. NPC sample which exhibited significant genomic instability had the shortest survival, potentially linked to multiple defective DNA repair genes. This study utilized long-read sequencing to identify a complex spectrum of genetic alterations, including numerous SVs and potentially pathogenic STRs, in Indonesian NPC. Extensive DNA repair gene defects, primarily complex SVs detectable by long reads, were observed and highly possibly associated with poor survival. These findings underscore the potential of long-read sequencing for uncovering clinically relevant mutations in NPC.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40594369"
},
{
- "id": "pmid:23770070",
+ "id": "pmid:40552959",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23770070",
- "title": "Identification of mucins by using a method involving a combination of on-membrane chemical deglycosylation and immunostaining.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/40552959",
+ "title": "Polyalanine Expansion in PABPN1 Alters the Structure and Dynamics of Its Nuclear Aggregates in Differentiated Muscle Cells.",
"type": "article-journal",
- "doi": "10.1016/j.jim.2013.06.002",
+ "doi": "10.1096/fj.202501097r",
"authors": [
- ["Yu-ki", "Matsuno"],
- ["Weijie", "Dong"],
- ["Seiya", "Yokoyama"],
- ["Suguru", "Yonezawa"],
- ["Hisashi", "Narimatsu"],
- ["Akihiko", "Kameyama"]
+ ["Sander D", "Mallon"],
+ ["Erik", "Bos"],
+ ["Vahid", "Sheikhhassani"],
+ ["Milad", "Shademan"],
+ ["Lenard M", "Voortman"],
+ ["Alireza", "Mashaghi"],
+ ["Thomas H", "Sharp"],
+ ["Vered", "Raz"]
],
- "publisher": "Journal of immunological methods",
- "issn": "1872-7905",
- "date": "2013-06-14",
- "abstract": "The characterization of mucins is critically important for gaining insights into the molecular pathology of diseases, including cancers, as well as for the discovery of biomarkers for disease diagnosis. However, no practical method has yet been reported for identifying mucin proteins. Here, we report a technique for immunological identification of mucins separated by supported molecular matrix electrophoresis (SMME), a recently developed membrane electrophoresis method. The technique involves on-membrane deglycosylation of mucins by using mild periodate oxidation/base-catalyzed elimination, followed by immunostaining with an antibody that specifically recognizes the mucin tandem repeat (TR) peptide. We demonstrated the method's feasibility by using MUC1 derived from 2 cancer cell lines, T47D and HPAF-II. The present method shows potential as an alternative approach for the identification of mucins separated by SMME or blotted from conventional gel electrophoresis, on a PVDF membrane.",
+ "publisher": "FASEB journal : official publication of the Federation of American Societies for Experimental Biology",
+ "issn": "1530-6860",
+ "date": "2025-06-30",
+ "abstract": "Intracellular protein aggregation is a hallmark of aging and contributes to pathology in some age-associated diseases. In hereditary adult-onset neuromuscular diseases (NMDs), protein aggregates play a key role in disease onset and progression. The wild-type Poly(A) binding protein nuclear 1 (PABPN1) forms benign nuclear aggregates, whereas a short trinucleotide expansion leads to the formation of pathogenic aggregates, a hallmark of Oculopharyngeal Muscular Dystrophy (OPMD). In OPMD, the mutant PABPN1 causes skeletal muscle weakness. So far, the structural differences between benign and pathogenic protein aggregates and their effects on muscle cell biology remain poorly understood. We employed an array of advanced imaging modalities to explore the morphological differences between nuclear aggregates formed by non-pathogenic and pathogenic PABPN1 variants. Through analyses spanning micro- to nanoscale, we identified distinct structural features of aggregates formed by wild-type and expanded PABPN1. We demonstrate that these differences were more pronounced in differentiated muscle cells compared to proliferating cells. We further linked the structural features of PABPN1 aggregates to muscle cell biology, namely alterations in mitochondrial function and proteasomal activity. Our findings provide new insights into the structural distinctions between pathogenic and non-pathogenic aggregates and their implications for cellular dysfunction in NMDs.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23770070"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40552959"
},
{
- "id": "pmid:23652307",
+ "id": "pmid:39113268",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23652307",
- "title": "Autoantibodies to MUC1 glycopeptides cannot be used as a screening assay for early detection of breast, ovarian, lung or pancreatic cancer.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/39113268",
+ "title": "Different outcomes of endurance and resistance exercise in skeletal muscles of Oculopharyngeal muscular dystrophy.",
"type": "article-journal",
- "doi": "10.1038/bjc.2013.214",
+ "doi": "10.1002/jcsm.13546",
"authors": [
- ["B", "Burford"],
- ["A", "Gentry-Maharaj"],
- ["R", "Graham"],
- ["D", "Allen"],
- ["J W", "Pedersen"],
- ["A S", "Nudelman"],
- ["O", "Blixt"],
- ["E O", "Fourkala"],
- ["D", "Bueti"],
- ["A", "Dawnay"],
- ["J", "Ford"],
- ["R", "Desai"],
- ["L", "David"],
- ["P", "Trinder"],
- ["B", "Acres"],
- ["T", "Schwientek"],
- ["A", "Gammerman"],
- ["C A", "Reis"],
- ["L", "Silva"],
- ["H", "Os\u00f3rio"],
- ["R", "Hallett"],
- ["H H", "Wandall"],
- ["U", "Mandel"],
- ["M A", "Hollingsworth"],
- ["I", "Jacobs"],
- ["I", "Fentiman"],
- ["H", "Clausen"],
- ["J", "Taylor-Papadimitriou"],
- ["U", "Menon"],
- ["J M", "Burchell"]
+ ["Alexis", "Boulinguiez"],
+ ["Jamila", "Dhiab"],
+ ["Barbara", "Crisol"],
+ ["Laura", "Muraine"],
+ ["Ludovic", "Gaut"],
+ ["Corentin", "Rouxel"],
+ ["Justine", "Flaire"],
+ ["Hadidja-Rose", "Mouigni"],
+ ["M\u00e9gane", "Lemaitre"],
+ ["Benoit", "Giroux"],
+ ["Lucie", "Audoux"],
+ ["Benjamin", "SaintPierre"],
+ ["Arnaud", "Ferry"],
+ ["Vincent", "Mouly"],
+ ["Gillian", "Butler-Browne"],
+ ["Elisa", "Negroni"],
+ ["Alberto", "Malerba"],
+ ["Capucine", "Trollet"]
],
- "publisher": "British journal of cancer",
- "issn": "1532-1827",
- "date": "2013-05-07",
- "abstract": "Autoantibodies have been detected in sera before diagnosis of cancer leading to interest in their potential as screening/early detection biomarkers. As we have found autoantibodies to MUC1 glycopeptides to be elevated in early-stage breast cancer patients, in this study we analysed these autoantibodies in large population cohorts of sera taken before cancer diagnosis.",
+ "publisher": "Journal of cachexia, sarcopenia and muscle",
+ "issn": "2190-6009",
+ "date": "2024-08-07",
+ "abstract": "Exercise is widely considered to have beneficial impact on skeletal muscle aging. In addition, there are also several studies demonstrating a positive effect of exercise on muscular dystrophies. Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant inherited neuromuscular disorder caused by mutations in the PAPBN1 gene. These mutations consist in short (1-8) and meiotically stable GCN trinucleotide repeat expansions in its coding region responsible for the formation of PAPBN1 intranuclear aggregates. This study aims to characterize the effects of two types of chronic exercise, resistance and endurance, on the OPMD skeletal muscle phenotype using a relevant murine model of OPMD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23652307"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39113268"
},
{
- "id": "pmid:21998660",
+ "id": "pmid:36790141",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21998660",
- "title": "Mucin variable number tandem repeat polymorphisms and severity of cystic fibrosis lung disease: significant association with MUC5AC.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/36790141",
+ "title": "Frequency and type of cancers in myotonic dystrophy: A retrospective cross-sectional study.",
"type": "article-journal",
- "doi": "10.1371/journal.pone.0025452",
+ "doi": "10.1002/mus.27801",
"authors": [
- ["Xueliang", "Guo"],
- ["Rhonda G", "Pace"],
- ["Jaclyn R", "Stonebraker"],
- ["Clayton W", "Commander"],
- ["Anthony T", "Dang"],
- ["Mitchell L", "Drumm"],
- ["Ann", "Harris"],
- ["Fei", "Zou"],
- ["Dallas M", "Swallow"],
- ["Fred A", "Wright"],
- ["Wanda K", "O'Neal"],
- ["Michael R", "Knowles"]
+ ["Eleonora S", "D'Ambrosio"],
+ ["Kathy", "Chuang"],
+ ["William S", "David"],
+ ["Anthony A", "Amato"],
+ ["Paloma", "Gonzalez-Perez"]
],
- "publisher": "PloS one",
- "issn": "1932-6203",
- "date": "2011-10-06",
- "abstract": "Variability in cystic fibrosis (CF) lung disease is partially due to non-CFTR genetic modifiers. Mucin genes are very polymorphic, and mucins play a key role in the pathogenesis of CF lung disease; therefore, mucin genes are strong candidates as genetic modifiers. DNA from CF patients recruited for extremes of lung phenotype was analyzed by Southern blot or PCR to define variable number tandem repeat (VNTR) length polymorphisms for MUC1, MUC2, MUC5AC, and MUC7. VNTR length polymorphisms were tested for association with lung disease severity and for linkage disequilibrium (LD) with flanking single nucleotide polymorphisms (SNPs). No strong associations were found for MUC1, MUC2, or MUC7. A significant association was found between the overall distribution of MUC5AC VNTR length and CF lung disease severity (p = 0.025; n = 468 patients); plus, there was robust association of the specific 6.4 kb HinfI VNTR fragment with severity of lung disease (p = 6.2\u00d710(-4) after Bonferroni correction). There was strong LD between MUC5AC VNTR length modes and flanking SNPs. The severity-associated 6.4 kb VNTR allele of MUC5AC was confirmed to be genetically distinct from the 6.3 kb allele, as it showed significantly stronger association with nearby SNPs. These data provide detailed respiratory mucin gene VNTR allele distributions in CF patients. Our data also show a novel link between the MUC5AC 6.4 kb VNTR allele and severity of CF lung disease. The LD pattern with surrounding SNPs suggests that the 6.4 kb allele contains, or is linked to, important functional genetic variation.",
+ "publisher": "Muscle & nerve",
+ "issn": "1097-4598",
+ "date": "2023-03-27",
+ "abstract": "Myotonic dystrophies (DMs) are autosomal dominant diseases in which expression of a mutant expanded repeat mRNA leads to abnormal splicing of downstream effector genes thought to be responsible for their multisystem involvement. Cancer risk and cancer-related deaths are increased in DM patients relative to the general population. We aimed at determining the frequency and type of cancers in both DM1 and DM2 vs a non-DM muscular dystrophy cohort.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21998660"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36790141"
},
{
- "id": "pmid:21385452",
+ "id": "pmid:34225694",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21385452",
- "title": "Autoantibodies to aberrantly glycosylated MUC1 in early stage breast cancer are associated with a better prognosis.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/34225694",
+ "title": "A Japanese case of oculopharyngeal muscular dystrophy (OPMD) with PABPN1 c.35G\u2009>\u2009C; p.Gly12Ala point mutation.",
"type": "article-journal",
- "doi": "10.1186/bcr2841",
+ "doi": "10.1186/s12883-021-02300-x",
"authors": [
- ["Ola", "Blixt"],
- ["Deanna", "Bueti"],
- ["Brian", "Burford"],
- ["Diane", "Allen"],
- ["Sylvain", "Julien"],
- ["Michael", "Hollingsworth"],
- ["Alex", "Gammerman"],
- ["Ian", "Fentiman"],
- ["Joyce", "Taylor-Papadimitriou"],
- ["Joy M", "Burchell"]
+ ["Yo-Suke", "Nishii"],
+ ["Yu-Ichi", "Noto"],
+ ["Rei", "Yasuda"],
+ ["Takamasa", "Kitaoji"],
+ ["Shinji", "Ashida"],
+ ["Eijirou", "Tanaka"],
+ ["Narihiro", "Minami"],
+ ["Ichizo", "Nishino"],
+ ["Toshiki", "Mizuno"]
],
- "publisher": "Breast cancer research : BCR",
- "issn": "1465-542X",
- "date": "2011-03-08",
- "abstract": "Detection of serum biomarkers for early diagnosis of breast cancer remains an important goal. Changes in the structure of O-linked glycans occur in all breast cancers resulting in the expression of glycoproteins that are antigenically distinct. Indeed, the serum assay widely used for monitoring disease progression in breast cancer (CA15.3), detects a glycoprotein (MUC1), but elevated levels of the antigen cannot be detected in early stage patients. However, since the immune system acts to amplify the antigenic signal, antibodies can be detected in sera long before the antigen. We have exploited the change in O-glycosylation to measure autoantibody responses to cancer-associated glycoforms of MUC1 in sera from early stage breast cancer patients.",
+ "publisher": "BMC neurology",
+ "issn": "1471-2377",
+ "date": "2021-07-05",
+ "abstract": "Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscular dystrophy characterised by slowly progressive ptosis, dysphagia, and proximal limb muscle weakness. A common cause of OPMD is the short expansion of a GCG or GCA trinucleotide repeat in PABPN1 gene.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21385452"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34225694"
},
{
- "id": "pmid:20876819",
+ "id": "pmid:27980005",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/20876819",
- "title": "Detection of circulating anti-mucin 1 (MUC1) antibodies in breast tumor patients by indirect enzyme-linked immunosorbent assay using a recombinant MUC1 protein containing six tandem repeats and expressed in Escherichia coli.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27980005",
+ "title": "Characterization of",
"type": "article-journal",
- "doi": "10.1128/cvi.00142-10",
+ "doi": "10.1136/jim-2016-000184",
"authors": [
- ["Yan", "Tang"],
- ["Li", "Wang"],
- ["Peiyin", "Zhang"],
- ["Hongfei", "Wei"],
- ["Rui", "Gao"],
- ["Xinming", "Liu"],
- ["Yongli", "Yu"],
- ["Liying", "Wang"]
+ ["Marisa", "Cruz-Aguilar"],
+ ["Caroline", "Guerrero-de Ferran"],
+ ["Jose Luis", "Tovilla-Canales"],
+ ["Angel", "Nava-Casta\u00f1eda"],
+ ["Juan C", "Zenteno"]
],
- "publisher": "Clinical and vaccine immunology : CVI",
- "issn": "1556-679X",
- "date": "2010-09-28",
- "abstract": "Mucin 1 (MUC1), a tumor-associated antigen, is a transmembrane glycoprotein expressed by normal epithelial cells and overexpressed by carcinomas of epithelial origin. Autoantibodies against MUC1 are often found in circulation, either free or bound to immune complexes, which might contribute to limit tumor outgrowth and dissemination by antibody-dependent cell-mediated cytotoxicity, and were found favorably predictive of survival in early breast cancer patients. There is no commercial enzyme-linked immunosorbent assay (ELISA) kit for detecting the anti-MUC1 antibodies in human serum thus far. To detect circulating anti-MUC1 antibodies, we established an indirect ELISA (I-ELISA) using a recombinant MUC1 protein containing six tandem repeat sequences of MUC1 after the antigenicity and specificity of the protein were confirmed. The I-ELISA had a sensitivity of 91.3% and a specificity of 94.1% when a competitive I-ELISA was used as a reference test. The results showed that more patients with benign breast tumors (P = 0.001) and breast cancer patients before primary treatment (P = 0.010) were found to have anti-MUC1 IgG than healthy women; anti-MUC1 IgG before primary treatment was found more than after primary treatment (P = 0.016) in breast cancer patients. Interestingly, the anti-MUC1 IgG serum level was reversely correlated to that of CA15-3 antigen in advanced-stage patients (r = -0.4294, P = 0.046). Our study has demonstrated the suitability of the established I-ELISA for detecting circulating anti-MUC1 antibodies in human serum. Furthermore, we found that circulating anti-MUC1 antibodies may still bind MUC1 shed into blood in stage IV breast cancer, which can support the use of MUC1-target immune therapy strategies.",
+ "publisher": "Journal of investigative medicine : the official publication of the American Federation for Clinical Research",
+ "issn": "1708-8267",
+ "date": "2016-12-15",
+ "abstract": "Oculopharyngeal muscular dystrophy (OPMD) is an autosomal-dominant, adult-onset disorder defined by blepharoptosis, dysphagia, and proximal muscle weakness. OPMD arises from heterozygous expansions of a trinucleotide (GCN) tract situated at the 5' region of the polyadenylate RNA binding protein 1 (",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20876819"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27980005"
},
{
- "id": "pmid:19811637",
+ "id": "pmid:26428746",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/19811637",
- "title": "Phase I dose escalation pharmacokinetic assessment of intravenous humanized anti-MUC1 antibody AS1402 in patients with advanced breast cancer.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26428746",
+ "title": "A South African family with oculopharyngeal muscular dystrophy: Clinical and molecular genetic characteristics.",
"type": "article-journal",
- "doi": "10.1186/bcr2409",
+ "doi": "10.7196/samjnew.7880",
"authors": [
- ["Mark D", "Pegram"],
- ["Virginia F", "Borges"],
- ["Nuhad", "Ibrahim"],
- ["Jyotsna", "Fuloria"],
- ["Charles", "Shapiro"],
- ["Susan", "Perez"],
- ["Karen", "Wang"],
- ["Franziska", "Schaedli Stark"],
- ["Nigel", "Courtenay Luck"]
+ ["Clara Maria", "Schutte"],
+ ["Cecelia M", "Dorfling"],
+ ["Riaan", "van Coller"],
+ ["Engela M", "Honey"],
+ ["Elizabeth Jansen", "van Rensburg"]
],
- "publisher": "Breast cancer research : BCR",
- "issn": "1465-542X",
- "date": "2009-01-01",
- "abstract": "MUC1 is a cell-surface glycoprotein that establishes a molecular barrier at the epithelial surface and engages in morphogenetic signal transduction. Alterations in MUC1 glycosylation accompany the development of cancer and influence cellular growth, differentiation, transformation, adhesion, invasion, and immune surveillance. A 20-amino-acid tandem repeat that forms the core protein of MUC1 is overexpressed and aberrantly glycosylated in the majority of epithelial tumors. AS1402 (formerly R1550) is a humanized IgG1k monoclonal antibody that binds to PDTR sequences within this tandem repeat that are not exposed in normal cells. AS1402 is a potent inducer of antibody-dependent cellular cytotoxicity (ADCC), specifically against MUC1-expressing tumor cells. The objective of this study was to determine the safety, tolerability, and pharmacokinetic (PK) characteristics of AS1402 monotherapy in patients with locally advanced or metastatic MUC1-positive breast cancer that had progressed after anthracyclines- and taxane-based therapy.",
+ "publisher": "South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde",
+ "issn": "0256-9574",
+ "date": "2015-09-21",
+ "abstract": "Autosomal dominantly inherited oculopharyngeal muscular dystrophy (OPMD) is caused by a trinucleotide repeat expansion in exon 1 of the polyadenylate binding protein nuclear 1 (PABPN1) gene on chromosome 14q. A large family with OPMD was recently identified in Pretoria, South Africa (SA). Molecular studies revealed a (GCG)11(GCA)3GCG or (GCN)15 mutant allele. The (GCN)15 mutation detected in this family has been described previously in families from Uruguay and Mexico as a founder effect. To our knowledge, this is the first report of an SA Afrikaner family with molecularly confirmed OPMD. The proband, a 64-year-old woman, presented to the neurology outpatient department at Steve Biko Academic Hospital, Pretoria. A sibship of 18 individuals was identified, of whom eight had OPMD. Four patients were interviewed and examined clinically, and electromyographic studies were performed. Molecular analysis of the PABPN1 gene was performed by polymerase chain reaction amplification and direct sequencing of exon 1 in three of the patients. Patients presented with ptosis, external ophthalmoplegia, dysphagia, dysarthria and mild proximal weakness. High foot arches and absent ankle reflexes raised the possibility of peripheral neuropathy, but electromyography showed only mildly low sensory amplitudes, and myopathic units in two patients.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19811637"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26428746"
},
{
- "id": "pmid:19625949",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/19625949",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:19625949']' timed out after 3 seconds"
+ "id": "pmid:23793615",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23793615",
+ "title": "A decline in PABPN1 induces progressive muscle weakness in oculopharyngeal muscle dystrophy and in muscle aging.",
+ "type": "article-journal",
+ "doi": "10.18632/aging.100567",
+ "authors": [
+ ["Seyed Yahya", "Anvar"],
+ ["Yotam", "Raz"],
+ ["Nisha", "Verway"],
+ ["Barbara", "van der Sluijs"],
+ ["Andrea", "Venema"],
+ ["Jelle J", "Goeman"],
+ ["John", "Vissing"],
+ ["Silv\u00e8re M", "van der Maarel"],
+ ["Peter A C", "'t Hoen"],
+ ["Baziel G M", "van Engelen"],
+ ["Vered", "Raz"]
+ ],
+ "publisher": "Aging",
+ "issn": "1945-4589",
+ "date": "2013-06-01",
+ "abstract": "Oculopharyngeal muscular dystrophy (OPMD) is caused by trinucleotide repeat expansion mutations in Poly(A) binding protein 1 (PABPN1). PABPN1 is a regulator of mRNA stability and is ubiquitously expressed. Here we investigated how symptoms in OPMD initiate only at midlife and why a subset of skeletal muscles is predominantly affected. Genome-wide RNA expression profiles from Vastus lateralis muscles human carriers of expanded-PABPN1 at pre-symptomatic and symptomatic stages were compared with healthy controls. Major expression changes were found to be associated with age rather than with expression of expanded-PABPN1, instead transcriptomes of OPMD and elderly muscles were significantly similar (P<0.05). Using k-means clustering we identified age-dependent trends in both OPMD and controls, but trends were often accelerated in OPMD. We report an age-regulated decline in PABPN1 levels in Vastus lateralis muscles from the fifth decade. In concurrence with severe muscle degeneration in OPMD, the decline in PABPN1 accelerated in OPMD and was specific to skeletal muscles. Reduced PABPN1 levels (30% to 60%) in muscle cells induced myogenic defects and morphological signatures of cellular aging in proportion to PABPN1 expression levels. We suggest that PABPN1 levels regulate muscle cell aging and OPMD represents an accelerated muscle aging disorder.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23793615"
},
{
- "id": "pmid:19534821",
+ "id": "pmid:21647273",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/19534821",
- "title": "Induction of protective and therapeutic anti-pancreatic cancer immunity using a reconstructed MUC1 DNA vaccine.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21647273",
+ "title": "A GCG expansion (GCG)\u2081\u2081 in polyadenylate-binding protein nuclear 1 gene caused oculopharyngeal muscular dystrophy in a Chinese family.",
"type": "article-journal",
- "doi": "10.1186/1471-2407-9-191",
+ "doi": "",
"authors": [
- ["Yefei", "Rong"],
- ["Dayong", "Jin"],
- ["Wenchuan", "Wu"],
- ["Wenhui", "Lou"],
- ["Danshong", "Wang"],
- ["Tiantao", "Kuang"],
- ["Xiaoling", "Ni"],
- ["Xinyu", "Qin"]
+ ["Juan", "Ye"],
+ ["Huina", "Zhang"],
+ ["Yandan", "Zhou"],
+ ["Han", "Wu"],
+ ["Changjun", "Wang"],
+ ["Xin", "Shi"]
],
- "publisher": "BMC cancer",
- "issn": "1471-2407",
- "date": "2009-06-18",
- "abstract": "Pancreatic cancer is a common, highly lethal disease with a rising incidence. MUC1 is a tumor-associated antigen that is over-expressed in pancreatic adenocarcinoma. Active immunotherapy that targets MUC1 could have great treatment value. Here we investigated the preventive and therapeutic effect of a MUC1 DNA vaccine on the pancreatic cancer.",
+ "publisher": "Molecular vision",
+ "issn": "1090-0535",
+ "date": "2011-05-25",
+ "abstract": "To identify the mutation in polyadenylate-binding protein nuclear 1 gene (PABPN1, previously termed PABP2) in a Chinese family with autosomal, dominantly inherited oculopharyngeal muscular dystrophy (OPMD).",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19534821"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21647273"
},
{
- "id": "pmid:18021186",
+ "id": "pmid:21602480",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/18021186",
- "title": "Generation of MUC1-stimulated mononuclear cells using optimized conditions.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21602480",
+ "title": "Delayed diagnosis of oculopharyngeal muscular dystrophy in Scotland.",
"type": "article-journal",
- "doi": "10.1111/j.1365-3083.2007.02032.x",
+ "doi": "10.1136/bjo.2010.200378",
"authors": [
- ["S E", "Wright"],
- ["R", "Khaznadar"],
- ["Z", "Wang"],
- ["I S", "Quinlin"],
- ["K A", "Rewers-Felkins"],
- ["C A", "Phillips"],
- ["S", "Patel"]
+ ["Pankaj Kumar", "Agarwal"],
+ ["David C", "Mansfield"],
+ ["Dorothy", "Mechan"],
+ ["Rustam", "Al-Shahi Salman"],
+ ["Richard J", "Davenport"],
+ ["Myles", "Connor"],
+ ["Richard", "Metcalfe"],
+ ["Richard", "Petty"]
],
- "publisher": "Scandinavian journal of immunology",
- "issn": "1365-3083",
- "date": "2007-11-15",
- "abstract": "Mucin is a glycoprotein found on the surface of cell membranes of adenocarcinomas. The purpose of these studies was to generate MUC1 multiple tandem repeat (VNTR)-stimulated mononuclear cells (M1SMC). We first determined the optimal conditions to influence the immune response. In these studies, peripheral blood mononuclear cells (PBMC), from patients with adenocarcinomas, were stimulated by different numbers of M1SMC stimulations, various concentrations of MUC1 peptide, washing of PBMC prior to stimulation and days in culture, to determine the optimal conditions to influence the immune response. The results of this study indicate that the mononuclear cells (MC) stimulated twice 1 week apart with MUC1 VNTR1 produced a greater specific killing of the breast cancer cell line MCF-7 than the 0, 1, 3 or 4 weekly stimulations. The optimal molarity for inducing cytotoxicity and cytokines (granulocyte macrophage colony-stimulating factor, gamma-interferon and interleukin-10) was 45 x 10(-8) M (1 microg/ml); except for tumour necrosis factor (TNF)-alpha which was 22 x 10(-8) M (0.5 microg/ml). The unwashed MC were superior to washing them with Ficoll-Hypaque. The optimal number of days in culture for cytotoxicity and cytokine production was after two stimulations (i.e. after day 7). Optimum conditions for generation of M1SMC identified in these studies were two stimulations with peptide, concentration of 45 x 10(-8) M (1 microg/ml) peptide, unwashed cells, and after two stimulations or after 8 days in culture. M1SMC were generated from multiple patients with breast cancer which lysed adenocarcinoma cells.",
+ "publisher": "The British journal of ophthalmology",
+ "issn": "1468-2079",
+ "date": "2011-05-20",
+ "abstract": "Oculopharyngeal muscular dystrophy (OPMD) presents with progressive ptosis, dysphagia and limb girdle weakness, and is caused by expansion of a trinucleotide tandem repeat within the gene encoding poly-(A) binding protein 2.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18021186"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21602480"
},
{
- "id": "pmid:17694298",
+ "id": "pmid:21316245",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/17694298",
- "title": "DNA aptamers against the MUC1 tumour marker: design of aptamer-antibody sandwich ELISA for the early diagnosis of epithelial tumours.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21316245",
+ "title": "Mutation and haplotype analysis of oculopharyngeal muscular dystrophy in Thai patients.",
"type": "article-journal",
- "doi": "10.1007/s00216-007-1470-1",
+ "doi": "10.1016/j.jocn.2010.08.020",
"authors": [
- ["C S M", "Ferreira"],
- ["K", "Papamichael"],
- ["G", "Guilbault"],
- ["T", "Schwarzacher"],
- ["J", "Gariepy"],
- ["S", "Missailidis"]
+ ["T", "Pulkes"],
+ ["C", "Papsing"],
+ ["M", "Busabaratana"],
+ ["C", "Dejthevaporn"],
+ ["R", "Witoonpanich"]
],
- "publisher": "Analytical and bioanalytical chemistry",
- "issn": "1618-2650",
- "date": "2007-08-11",
- "abstract": "Aptamers are functional molecules able to bind tightly and selectively to disease markers, offering great potential for applications in disease diagnosis and therapy. MUC1 is a well-known tumour marker present in epithelial malignancies and is used in immunotherapeutic and diagnostic approaches. We report the selection of DNA aptamers that bind with high affinity and selectivity an MUC1 recombinant protein containing five repeats of the variable tandem repeat region. Aptamers were selected using the SELEX methodology from an initial library containing a 25-base-long variable region for their ability to bind to the unglycosylated form of the MUC1 protein. After ten rounds of in vitro selection and amplification, more than 90% of the pool of sequences consisted of target-binding molecules, which were cloned, sequenced and found to share no sequence consensus. The binding properties of these aptamers were quantified using ELISA and surface plasmon resonance. The lead aptamer sequence was subsequently used in the design of an aptamer-antibody hybrid sandwich ELISA for the identification and quantification of MUC1 in buffered solutions. Following optimisation of the operating conditions, the resulting enzyme immunoassay displayed an EC50 value of 25 microg/ml, a detection limit of 1 microg/ml and a linear range between 8 and 100 microg/ml for the MUC1 five tandem repeat analyte. In addition, recovery studies performed in buffer conditions resulted in averaged recoveries between 98.2 and 101.7% for all spiked samples, demonstrating the usability of the aptamer as a receptor in microtitre-based assays. Our results aim towards the formation of new diagnostic assays against this tumour marker for the early diagnosis of primary or metastatic disease in breast, bladder and other epithelial tumours.",
+ "publisher": "Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia",
+ "issn": "1532-2653",
+ "date": "2011-05-01",
+ "abstract": "Oculopharyngeal muscular dystrophy (OPMD) is an inherited neuromuscular disease associated with a short trinucleotide repeat expansion in Exon 1 of the PABPN1 gene. OPMD is uncommon in East Asian populations, and there have been no previous reports of Thai patients. We studied clinical and molecular genetic features of six unrelated Thai patients with autosomal dominant OPMD. All patients had expansions of the guanine-cytosine-guanine (GCG) repeat ranging from three to seven additional repeats in the PABPN1 gene. Haplotype analysis showed that these mutations might have originated independently. Analysis of the size of the GCG repeat in the PABPN1 gene in 200 Thai control patients showed that 0.5% of the control subjects possessed (GCG)(7), thereby suggesting that the prevalence of autosomal recessive OPMD in the Thai population was approximately 1 in 160,000. In conclusion, our data suggest that OPMD in Thailand may be more common than previously thought.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17694298"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21316245"
},
{
- "id": "pmid:17581677",
+ "id": "pmid:18343218",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/17581677",
- "title": "No evidence of association of MUC-1 genetic polymorphism with embryo implantation failure.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18343218",
+ "title": "Induction of expression and co-localization of heat shock polypeptides with the polyalanine expansion mutant of poly(A)-binding protein N1 after chemical stress.",
"type": "article-journal",
- "doi": "10.1590/s0100-879x2007000600007",
+ "doi": "10.1016/j.bbrc.2008.02.162",
"authors": [
- ["D B", "Dentillo"],
- ["F R P", "Souza"],
- ["J", "Meola"],
- ["G S", "Vieira"],
- ["M E H D", "Yazlle"],
- ["L R", "Goulart"],
- ["L", "Martelli"]
+ ["Qishan", "Wang"],
+ ["Jnanankur", "Bag"]
],
- "publisher": "Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica",
- "issn": "0100-879X",
- "date": "2007-06-01",
- "abstract": "Pregnancy loss can be caused by several factors involved in human reproduction. Although up to 50% of cases remain unexplained, it has been postulated that the major cause of failed pregnancy is an error of embryo implantation. Transmembrane mucin-1 (MUC-1) is a glycoprotein expressed on the endometrial cell surface which acts as a barrier to implantation. The gene that codes for this molecule is composed of a polymorphic tandem repeat of 60 nucleotides. Our objective was to determine if MUC-1 genetic polymorphism is associated with implantation failure in patients with a history of recurrent abortion. The study was conducted on 10 women aged 25 to 35 years with no history of successful pregnancy and with a diagnosis of infertility. The control group consisted of 32 patients aged 25 to 35 years who had delivered at least two full-term live children and who had no history of abortions or fetal losses. MUC-1 amplicons were obtained by PCR and observed on agarose and polyacrylamide gel after electrophoresis. Statistical analysis showed no significant difference in the number of MUC-1 variable number of tandem repeats between these groups (P > 0.05). Our results suggest that there is no effect of the polymorphic MUC-1 sequence on the implantation failure. However, the data do not exclude MUC-1 relevance during embryo implantation. The process is related to several associated factors such as the mechanisms of gene expression in the uterus, specific MUC-1 post-translational modifications and appropriate interactions with other molecules during embryo implantation.",
+ "publisher": "Biochemical and biophysical research communications",
+ "issn": "1090-2104",
+ "date": "2008-03-14",
+ "abstract": "Formation of nuclear inclusions consisting of aggregates of a polyalanine expansion mutant of nuclear poly(A)-binding protein (PABPN1) is the hallmark of oculopharyngeal muscular dystrophy (OPMD). OPMD is a late onset autosomal dominant disease. Patients with this disorder exhibit progressive swallowing difficulty and drooping of their eye lids, which starts around the age of 50. Previously we have shown that treatment of cells expressing the mutant PABPN1 with a number of chemicals such as ibuprofen, indomethacin, ZnSO(4), and 8-hydroxy-quinoline induces HSP70 expression and reduces PABPN1 aggregation. In these studies we have shown that expression of additional HSPs including HSP27, HSP40, and HSP105 were induced in mutant PABPN1 expressing cells following exposure to the chemicals mentioned above. Furthermore, all three additional HSPs were translocated to the nucleus and probably helped to properly fold the mutant PABPN1 by co-localizing with this protein.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17581677"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18343218"
},
{
- "id": "pmid:17050588",
+ "id": "pmid:17138075",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/17050588",
- "title": "Identification of a novel cancer-specific immunodominant glycopeptide epitope in the MUC1 tandem repeat.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17138075",
+ "title": "Identification of a novel mutation in a Korean patient with oculopharyngeal muscular dystrophy.",
"type": "article-journal",
- "doi": "10.1093/glycob/cwl061",
+ "doi": "10.1016/j.jocn.2005.12.036",
"authors": [
- ["Mads A", "Tarp"],
- ["Anne Louise", "S\u00f8rensen"],
- ["Ulla", "Mandel"],
- ["Hans", "Paulsen"],
- ["Joy", "Burchell"],
- ["Joyce", "Taylor-Papadimitriou"],
- ["Henrik", "Clausen"]
+ ["Jong Seok", "Bae"],
+ ["Chang-Seok", "Ki"],
+ ["Jong-Won", "Kim"],
+ ["Byoung Joon", "Kim"]
],
- "publisher": "Glycobiology",
- "issn": "0959-6658",
- "date": "2006-10-18",
- "abstract": "The cell membrane mucin MUC1 is over-expressed and aberrantly glycosylated in many cancers, and cancer-associated MUC1 glycoforms represent potential targets for immunodiagnostic and therapeutic measures. We have recently shown that MUC1 with GalNAcalpha1-O-Ser/Thr (Tn) and NeuAcalpha2-6GalNAcalpha1-O-Ser/Thr (STn) O-glycosylation is a cancer-specific glycoform, and that Tn/STn-MUC1 glycopeptide-based vaccines can override tolerance in human MUC1 transgenic mice and induce humoral immunity with high specificity for MUC1 cancer-specific glycoforms (Sorensen AL, Reis CA, Tarp MA, Mandel U, Ramachandran K, Sankaranarayanan V, Schwientek T, Graham R, Taylor-Papadimitriou J, Hollingsworth MA, et al. 2006. Chemoenzymatically synthesized multimeric Tn/STn MUC1 glycopeptides elicit cancer-specific anti-MUC1 antibody responses and override tolerance. Glycobiology. 16:96-107). In order to further characterize the immune response to Tn/STn-MUC1 glycoforms, we generated monoclonal antibodies with specificity similar to the polyclonal antibody response found in transgenic mice. In the present study, we define the immunodominant epitope on Tn/STn-MUC1 glycopeptides to the region including the amino acids GSTA of the MUC1 20-amino acid tandem repeat (HGVTSAPDTRPAPGSTAPPA). Most other MUC1 antibodies are directed to the PDTR region, although patients with antibodies to the GSTA region have been identified. A panel of other MUC1 glycoform-specific monoclonal antibodies was included for comparison. The study demonstrates that the GSTA region of the MUC1 tandem repeat contains a highly immunodominant epitope when presented with immature short O-glycans. The cancer-specific expression of this glycopeptide epitope makes it a prime candidate for immunodiagnostic and therapeutic measures.",
+ "publisher": "Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia",
+ "issn": "0967-5868",
+ "date": "2007-01-01",
+ "abstract": "Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscle disorder characterized by progressive dysphagia and bilateral ptosis. Mutations in the polyadenylate binding protein nuclear 1 (PABPN1) gene have been found to cause OPMD. The typical mutation is a stable trinucleotide repeat expansion in the first exon of the PABPN1 gene, in which (GCG)(6) is the normal repeat length. We investigated a Korean patient with OPMD and identified a novel mutation: a heterozygous insertion of a 9-bp sequence [(GCG)(GCA)(GCA); c.27_28insGCGGCAGCA] instead of the (GCG) repeat expansion, resulting in an in-frame insertion of three alanines (p.A10insAAA). To the best of our knowledge, this is the first report of a genetically confirmed case of OPMD in Korea.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17050588"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17138075"
},
{
- "id": "pmid:16631167",
+ "id": "pmid:16378590",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/16631167",
- "title": "MUC1 splice variants in human ocular surface tissues: possible differences between dry eye patients and normal controls.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/16378590",
+ "title": "Ectopic expression of a polyalanine expansion mutant of poly(A)-binding protein N1 in muscle cells in culture inhibits myogenesis.",
"type": "article-journal",
- "doi": "10.1016/j.exer.2006.01.031",
+ "doi": "10.1016/j.bbrc.2005.12.078",
"authors": [
- ["Yoannis", "Imbert"],
- ["Douglas S", "Darling"],
- ["Marcia M", "Jumblatt"],
- ["Gary N", "Foulks"],
- ["Erica G", "Couzin"],
- ["Pamela S", "Steele"],
- ["William W", "Young"]
+ ["Qishan", "Wang"],
+ ["Jnanankur", "Bag"]
],
- "publisher": "Experimental eye research",
- "issn": "0014-4835",
- "date": "2006-04-21",
- "abstract": "Mucins are highly glycosylated proteins that are vital to the maintenance of healthy epithelial surfaces including the ocular surface. Mucins act as lubricants, protectants, and mediators of signal transduction. The majority of the O-glycosylation sites on the transmembrane mucin MUC1 are found in a highly polymorphic core region containing a variable number of tandem repeats (VNTR). MUC1 alleles can be divided into size classes that contain small (30-45) or large (60-90) numbers of repeats. Although at least 12 splice variants of MUC1 have been found in other tissues, no splice variants have been reported in human ocular surface tissues. We have used RT-PCR to identify MUC1 splice variants that were then confirmed by sequencing. We here report the presence in some samples of human cornea, conjunctiva, and lacrimal gland of MUC1/B which features canonical splicing between exons 1 and 2 and MUC1/A, a transcript that retains 27bp from the 3' end of intron 1 and is predicted to add 9 amino acids to the MUC1 sequence upstream of the tandem repeat region. Cornea and conjunctiva both contain the MUC1/SEC splice variant that lacks the transmembrane domain and, therefore, results in a soluble, secreted form of MUC1. Cornea and conjunctiva also contain MUC1/Y and MUC1/Z(X) variants that lack the tandem repeat region. Cornea, conjunctiva, and lacrimal gland also contain a previously undescribed MUC1 variant transcript, termed MUC1/YI, that retains 99bp from the 5' end and 27bp from the 3' end of the first intron, resulting in a frame shift and premature stop codon. This transcript is predicted to produce a novel 27 amino acid peptide after signal peptidase cleavage. Analysis of brush cytology samples revealed that the percentage of dry eye patients expressing the MUC1/A variant in the conjunctival epithelium is lower than in normal control donors. Western blotting confirmed that MUC1/A is associated with alleles containing the large size class of tandem repeats. Therefore, we propose that one factor in susceptibility to dry eye disease may be the lengths of the MUC1 VNTR in conjunctival epithelium based on the rationale that longer VNTR provide better lubrication and greater protection of the ocular surface against inflammation.",
+ "publisher": "Biochemical and biophysical research communications",
+ "issn": "0006-291X",
+ "date": "2005-12-21",
+ "abstract": "Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset dominant genetic disease caused by the expansion of a GCG trinucleotide repeat that encodes the polyalanine tract at the N-terminus of the nuclear poly(A)-binding protein (PABPN1). Presence of intranuclear inclusions (INIs) containing PABPN1 aggregates in the skeletal muscles is the hallmark of OPMD. Here, we show that ectopic expression of the mutant PABPN1 produced INIs in a muscle cell culture model and reduced expression of several muscle-specific proteins including alpha-actin, slow troponin C, muscle creatine kinase, and two myogenic transcription factors, myogenin and MyoD. However, the levels of two upstream regulators of the MyoD gene, the Myf-5 and Pax3/7, were not affected, but both proteins co-localized with the PABPN1 aggregates in the mutant PABPN1 overexpressing cells. In these cells, although myogenin and MyoD levels were reduced, these two transcription factors did not co-localize with the mutant PABPN1 aggregates. Therefore, sequestration of Myf5 and Pax3/7 by the mutant PABPN1 aggregates was a specific effect on these factors. Our results suggest that trapping of these two important myogenic determinants may interfere with an early step in myogenesis.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16631167"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16378590"
},
{
- "id": "pmid:16302687",
+ "id": "pmid:16239242",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/16302687",
- "title": "The production and characterization of novel heavy-chain antibodies against the tandem repeat region of MUC1 mucin.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/16239242",
+ "title": "Induction of HSP70 expression and recruitment of HSC70 and HSP70 in the nucleus reduce aggregation of a polyalanine expansion mutant of PABPN1 in HeLa cells.",
"type": "article-journal",
- "doi": "10.1080/08820130500265356",
+ "doi": "10.1093/hmg/ddi395",
"authors": [
- ["Fatemeh", "Rahbarizadeh"],
- ["Mohammad J", "Rasaee"],
- ["Mehdi", "Forouzandeh"],
- ["Abdolamir", "Allameh"],
- ["Ramin", "Sarrami"],
- ["Habib", "Nasiry"],
- ["Majid", "Sadeghizadeh"]
+ ["Qishan", "Wang"],
+ ["Dick D", "Mosser"],
+ ["Jnanankur", "Bag"]
],
- "publisher": "Immunological investigations",
- "issn": "0882-0139",
- "date": "2005-01-01",
- "abstract": "Camelidae are known to produce immunoglobulins (Igs) devoid of light chains and constant heavy-chain domains (CH1). Antigen-specific fragments of these heavy-chain IgGs (VHH) are of great interest in biotechnology applications. This paper describes the first example of successfully raised heavy-chain antibodies in Camelus dromedarius (single-humped camel) and Camelus bactrianus (two-humped camel) against a MUC1 related peptide that is found to be an important epitope expressed in cancerous tissue. Camels were immunized against a synthetic peptide corresponding to the tandem repeat region of MUC1 mucin and cancerous tissue preparation obtained from patients suffering from breast carcinoma. Three IgG subclasses with different binding properties to protein A and G were purified by affinity chromatography. Both conventional and heavy-chain IgG antibodies were produced in response to MUC1-related peptide. The elicited antibodies could react specifically with the tandem repeat region of MUC1 mucin in an enzyme linked immunosorbant assay (ELISA). Anti-peptide antibodies were purified after passing antiserum over two affinity chromatography columns. Using ELISA, immunocytochemistry and Western blotting, the interaction of purified antibodies with different antigens was evaluated. The antibodies were observed to be selectively bound to antigens namely: MUC1 peptide (tandem repeat region), human milk fat globule membrane (HMFG), deglycosylated human milk fat globule membrane (D-HMFG), homogenized cancerous breast tissue and a native MUC1 purified from ascitic fluid. Ka values of specific polyclonal antipeptide antibodies were estimated in C. dromedarius and C. bactrianus, as 7 x 10(10) M(-1) and 1.4 x 10(10) M(-1) respectively.",
+ "publisher": "Human molecular genetics",
+ "issn": "0964-6906",
+ "date": "2005-10-20",
+ "abstract": "Nuclear inclusions formed by the aggregation of a polyalanine expansion mutant of the nuclear poly(A)-binding protein (PABPN1) is a hallmark of oculopharyngeal muscular dystrophy (OPMD). OPMD is a dominant autosomal disease in which patients exhibit progressive difficulty of swallowing and eyelid elevation, starting around the age of 50. At present, there is no specific treatment to reduce the aggregate burden in patients. However, in cell culture models of OPMD, reduction of protein aggregation can be achieved by ectopic expression of HSP70. As gene transfer may not be the most effective means to elevate HSP70 levels, we tested four pharmacological agents for their ability to induce HSP70, recruit both HSP70 and HSC70 into the cell nucleus and reduce mutant PABPN1 aggregation in a HeLa cell culture model. We show here that exposure to moderate levels of ZnSO4, 8-hydroxyquinoline, ibuprofen and indomethacin produced a robust stress response resulting in the induction of HSP70 in HeLa cells expressing the mutant PABPN1 as a green fluorescent protein (GFP) fusion protein. Both HSP70 and the constitutive chaperone HSC70 localized in the nucleus of cells treated with any one of the four agents. This stress response was similar to what was observed following hyperthermia. All four agents also caused a significant reduction in the cellular burden of protein aggregates, as was judged by confocal microscopy and solubility changes of the aggregates. A concomitant reduction of cell death in drug-treated mutant PABPN1 expressing cells was also observed.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16302687"
-},
-{
- "id": "pmid:15944787",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/15944787",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:15944787']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16239242"
},
{
- "id": "pmid:15729696",
+ "id": "pmid:15811916",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/15729696",
- "title": "Responses of human T cells to peptides flanking the tandem repeat and overlapping the signal sequence of MUC1.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15811916",
+ "title": "In vivo aggregation properties of the nuclear poly(A)-binding protein PABPN1.",
"type": "article-journal",
- "doi": "10.1002/ijc.20949",
+ "doi": "10.1261/rna.7217105",
"authors": [
- ["Isabel", "Correa"],
- ["Timothy", "Plunkett"],
- ["Julia", "Coleman"],
- ["Eleni", "Galani"],
- ["Elisabeth", "Windmill"],
- ["Joy M", "Burchell"],
- ["Joyce", "Taylor-Papdimitriou"]
+ ["Jo\u00e3o Paulo", "Tavanez"],
+ ["Patricia", "Calado"],
+ ["Jos\u00e9", "Braga"],
+ ["Miguel", "Lafarga"],
+ ["Maria", "Carmo-Fonseca"]
],
- "publisher": "International journal of cancer",
- "issn": "0020-7136",
- "date": "2005-07-10",
- "abstract": "The epithelial mucin MUC1 is one of the few tumour-associated antigens identified for breast cancer. Several MUC1-derived peptides binding HLA-A*0201 molecules have been identified that correspond to sequences outside the tandem repeat. Immunisation with some of these peptides induces protective antitumour immunity in mice. Another HLA-A*0201-binding peptide has been identified in a human system. We have evaluated the CD8(+) T-cell responses to all these peptides using peripheral blood lymphocytes from breast cancer patients and normal donors. Specific CD8(+) T-cell responses could be generated in vitro against some of these peptides but only after several rounds of in vitro restimulation, and they did not recognise human cells endogenously expressing the antigen. Nevertheless, T cells recognised by HLA-A*0201 tetramers carrying a peptide from the signal sequence (LLLLTVLTV) could be detected in the peripheral blood of some HLA-A*0201(+) breast cancer patients but not in healthy adults. This peptide is the only one of those tested which was identified in the human system, and the results emphasize the potential problems involved in translation of data from laboratory animal models to the human system.",
+ "publisher": "RNA (New York, N.Y.)",
+ "issn": "1355-8382",
+ "date": "2005-04-05",
+ "abstract": "A broad range of degenerative diseases is associated with intracellular inclusions formed by toxic, aggregation-prone mutant proteins. Intranuclear inclusions constitute a pathological hallmark of oculopharyngeal muscular dystrophy (OPMD), a dominantly inherited disease caused by (GCG) repeat expansions in the gene that encodes for nuclear poly(A) binding protein (PABPN1). The mutation results in an extended polyalanine stretch that has been proposed to induce protein aggregation and formation of intranuclear inclusions. Here we show that normal PABPN1 is inherently aggregation-prone when exogenously expressed in either HeLa or myogenic C2 cells. Similar deposits of insoluble PABPN1 are formed by variant forms of the protein containing either a polyalanine expansion or a complete deletion of the polyalanine tract, indicating that the mutation responsible for OPMD is not essential for formation of PABPN1 inclusions. In contrast, interfering with any of the protein domains required for stimulation of poly(A) polymerase prevents the formation of inclusions. Most surprisingly, photobleaching experiments reveal that both normal and expanded PABPN1 molecules are not irreversibly sequestered into aggregates, but rather move rapidly in and out of the inclusions. These findings have important implications for the interpretation of OPMD model systems based on exogenous expression of PABPN1.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15729696"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15811916"
},
{
- "id": "pmid:15604091",
+ "id": "pmid:14627730",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/15604091",
- "title": "Thomsen-Friedenreich antigen expression in gastric carcinomas is associated with MUC1 mucin VNTR polymorphism.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/14627730",
+ "title": "Trinucleotide expansions leading to an extended poly-L-alanine segment in the poly (A) binding protein PABPN1 cause fibril formation.",
"type": "article-journal",
- "doi": "10.1093/glycob/cwi027",
+ "doi": "10.1110/ps.03214703",
"authors": [
- ["F", "Santos-Silva"],
- ["A", "Fonseca"],
- ["T", "Caffrey"],
- ["F", "Carvalho"],
- ["P", "Mesquita"],
- ["C", "Reis"],
- ["R", "Almeida"],
- ["L", "David"],
- ["M A", "Hollingsworth"]
+ ["Till", "Scheuermann"],
+ ["Barbe", "Schulz"],
+ ["Alfred", "Blume"],
+ ["Elmar", "Wahle"],
+ ["Rainer", "Rudolph"],
+ ["Elisabeth", "Schwarz"]
],
- "publisher": "Glycobiology",
- "issn": "0959-6658",
- "date": "2004-12-15",
- "abstract": "Aberrant glycosylation of mucins is a common phenomenon associated with oncogenic transformation. We investigated the association between expression of the tumor-associated antigens T, Tn, and sialyl-Tn and polymorphism in the length of the MUC1 mucin tandem repeat in a series of gastric carcinomas. We further evaluated the relevance of MUC1 tandem repeat length on the expression of these tumor-associated carbohydrate antigens (TACAs) using a gastric carcinoma cell line model expressing recombinant MUC1 constructs carrying 0, 3, 9, and 42 repeats. Gastric carcinomas showed a high prevalence of Tn and sialyl-Tn antigens, whereas T antigen was less frequently expressed. The expression of T antigen was significantly higher in gastric carcinomas from patients homozygous for MUC1 large tandem repeat alleles. No significant associations were found for Tn and sialyl-Tn antigens. This novel association was reinforced by the gastric carcinoma cell line model experiments, where de novo expression of T antigen was detected in clones transfected with larger VNTR regions. Our results indicate that polymorphism in the MUC1 tandem repeat influences the expression of TACAs in gastric cancer cells and may therefore allow the identification of subgroups of patients that develop more aggressive tumors expressing T antigen.",
+ "publisher": "Protein science : a publication of the Protein Society",
+ "issn": "0961-8368",
+ "date": "2003-12-01",
+ "abstract": "The nuclear poly(A) binding protein (PABPN1) stimulates poly(A) polymerase and controls the lengths of poly(A) tails during pre-mRNA processing. The wild-type protein possesses 10 consecutive Ala residues immediately after the start methionine. Trinucleotide expansions in the coding sequence result in an extension of the Ala stretch to maximal 17 Ala residues in total. Individuals carrying the trinucleotide expansions suffer from oculopharyngeal muscular dystrophy (OPMD). Intranuclear inclusions consisting predominantly of PABPN1 have been recognized as a pathological hallmark of the genetic disorder. To elucidate the molecular events that lead to disease, recombinant PABPN1, and N-terminal fragments of the protein with varying poly-L-alanine stretches were analyzed. As the full-length protein displayed a strong tendency to aggregate into amorphous deposits, soluble N-terminal fragments were also studied. Expansion of the poly-L-alanine sequence to the maximal length observed in OPMD patients led to an increase of alpha-helical structure. Upon prolonged incubation the protein was found in fibrils that showed all characteristics of amyloid-like fibers. The lag-phase of fibril formation could be reduced by seeding. Structural analysis of the fibrils indicated antiparallel beta-sheets.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15604091"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:14627730"
},
{
- "id": "pmid:15041735",
+ "id": "pmid:11712939",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/15041735",
- "title": "A human cytotoxic T-lymphocyte epitope and its agonist epitope from the nonvariable number of tandem repeat sequence of MUC-1.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11712939",
+ "title": "Oculopharyngeal muscular dystrophy in Hispanic New Mexicans.",
"type": "article-journal",
- "doi": "10.1158/1078-0432.ccr-1011-03",
+ "doi": "10.1001/jama.286.19.2437",
"authors": [
- ["Kwong-Yok", "Tsang"],
- ["Claudia", "Palena"],
- ["James", "Gulley"],
- ["Philip", "Arlen"],
- ["Jeffrey", "Schlom"]
+ ["M W", "Becher"],
+ ["L", "Morrison"],
+ ["L E", "Davis"],
+ ["W C", "Maki"],
+ ["M K", "King"],
+ ["J M", "Bicknell"],
+ ["B L", "Reinert"],
+ ["C", "Bartolo"],
+ ["D G", "Bear"]
],
- "publisher": "Clinical cancer research : an official journal of the American Association for Cancer Research",
- "issn": "1078-0432",
- "date": "2004-03-15",
- "abstract": "MUC-1/DF-3 remains an attractive target for vaccine therapy. It is overexpressed in the majority of human carcinomas and multiple myeloma. Clinical trials using MUC-1-based vaccines have demonstrated safety, clinical responses, and the induction of T-cell responses directed against MUC-1. Previous studies in experimental models and in clinical trials have demonstrated that altering the amino acid sequence of a \"self\" epitope can lead to the generation of an enhancer agonist epitope capable of eliciting stronger T-cell responses than the native epitope can.",
+ "publisher": "JAMA",
+ "issn": "0098-7484",
+ "date": "2001-11-21",
+ "abstract": "Oculopharyngeal muscular dystrophy (OPMD) is a rare myopathy caused by polyalanine triplet repeat expansion in the gene for poly(A) binding protein 2 (PABP2) and is found in isolated cohorts throughout the world. We have observed numerous cases of OPMD in New Mexico.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15041735"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11712939"
},
{
- "id": "pmid:14707484",
+ "id": "pmid:11087766",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/14707484",
- "title": "In vivo glycosylation of MUC1 in airway epithelial cells.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11087766",
+ "title": "Oculopharyngeal MD among Bukhara Jews is due to a founder (GCG)9 mutation in the PABP2 gene.",
"type": "article-journal",
- "doi": "10.1023/b:glyc.0000004009.24191.d3",
+ "doi": "10.1212/wnl.55.9.1267",
"authors": [
- ["Howard S", "Silverman"],
- ["Mark", "Sutton-Smith"],
- ["Paul", "Heal"],
- ["Simon", "Parry"],
- ["Timea", "Palmai-Pallag"],
- ["Shih-Hsing", "Leir"],
- ["Howard R", "Morris"],
- ["Anne", "Dell"],
- ["Ann", "Harris"]
+ ["S C", "Blumen"],
+ ["A D", "Korczyn"],
+ ["H", "Lavoie"],
+ ["S", "Medynski"],
+ ["J", "Chapman"],
+ ["A", "Asherov"],
+ ["P", "Nisipeanu"],
+ ["R", "Inzelberg"],
+ ["R L", "Carasso"],
+ ["J P", "Bouchard"],
+ ["F M", "Tom\u00e9"],
+ ["G A", "Rouleau"],
+ ["B", "Brais"]
],
- "publisher": "Glycoconjugate journal",
- "issn": "0282-0080",
- "date": "2002-07-01",
- "abstract": "The O-glycans that decorate mucin glycoproteins contribute to the biophysical and biochemical properties of these molecules and hence their function as a barrier and lubricant on epithelial surfaces. Alterations in mucin O-glycosylation in certain diseases may contribute to pathology. It is known that both the host cell type and the amino acid sequence of the mucin tandem repeat contribute to the O-glycosylation of a mucin molecule. We expressed an epitope-tagged MUC1 mucin cDNA construct in the airway cell line 16HBE14o- and the colon carcinoma cell line Caco2 and used Fast Atom Bombardment Mass Spectrometry to evaluate the contribution of the host cell to differences in O-glycosylation of a single mucin. Many of the glycans detected on the MUC1 mucin were common to both cell types, as would be predicted from biosynthetic constraints. However, MUC1 synthesized in the airway cell line showed comparatively low levels of sialylation but carried a range of oligo-N-acetyllactosamine structures that were not seen in the colon carcinoma cell line.",
+ "publisher": "Neurology",
+ "issn": "0028-3878",
+ "date": "2000-11-14",
+ "abstract": "To determine whether all cases of oculopharyngeal muscular dystrophy (OPMD) among Bukhara Jews share the same founder mutation.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:14707484"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11087766"
},
{
- "id": "pmid:12747745",
+ "id": "pmid:11003790",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/12747745",
- "title": "MUC1-like tandem repeat proteins are broadly immunogenic in cancer patients.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11003790",
+ "title": "Nuclear accumulation of expanded PABP2 gene product in oculopharyngeal muscular dystrophy.",
"type": "article-journal",
- "doi": "",
+ "doi": "10.1002/1097-4598(200010)23:10<1549::aid-mus11>3.0.co;2-0",
"authors": [
- ["Joseph A", "Mollick"],
- ["F Stephen", "Hodi"],
- ["Robert J", "Soiffer"],
- ["Lee M", "Nadler"],
- ["Glenn", "Dranoff"]
+ ["E", "Uyama"],
+ ["T", "Tsukahara"],
+ ["K", "Goto"],
+ ["Y", "Kurano"],
+ ["M", "Ogawa"],
+ ["Y J", "Kim"],
+ ["M", "Uchino"],
+ ["K", "Arahata"]
],
- "publisher": "Cancer immunity",
- "issn": "1424-9634",
- "date": "2003-03-17",
- "abstract": "The identification of antigens mediating tumor rejection is an important goal of cancer immunology. The SEREX technology utilizes antibodies from cancer patients to identify candidate antigens from tumor-derived cDNA expression libraries. Using sera from a long-term surviving metastatic melanoma patient vaccinated with irradiated, autologous tumor cells engineered to secrete granulocyte-macrophage colony stimulating factor (GM-CSF), we identified an antigen reported to be a putative opioid growth factor receptor (OGFr). The human immune response to OGFr exhibits three features shared with other tumor antigens. First, the protein is an intracellular antigen found in both nucleus and cytoplasm. Second, part of the antibody response is directed at a putative protein product encoded by an alternative reading frame (ARF). Third, part of the antibody response is directed at a portion of the molecule that bears a striking resemblance to the extracellular domain of MUC1, both with respect to primary structure and size polymorphism. Antibody responses to OGFr and a synthetic peptide representing a putative alternative reading frame product (OGFr-ARF) were frequently found in cancer patients. 11/45 (24%) melanoma patients had antibodies to OGFr and 5/45 (11%) had antibodies to OGFr-ARF. Moreover, 5/24 (21%) lung cancer, 4/25 (16%) prostate cancer, and 5/6 breast or ovarian cancer patients had antibodies to OGFr, the alternative frame product, or both. These data add to the growing list of tumor antigens that appear to be translated in two frames, and suggest that OGFr and OGFr-ARF may be useful targets for vaccination.",
+ "publisher": "Muscle & nerve",
+ "issn": "0148-639X",
+ "date": "2000-10-01",
+ "abstract": "Autosomal dominant oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disease caused by (GCG) repeat expansions in exon 1 of the poly(A) binding protein 2 gene (PABP2). To elucidate the molecular mechanism underlying the disease, we raised an antiserum against a synthetic peptide fragment predicted from PABP2 cDNA. The peptide corresponded to amino acids 271-291 where a cluster of posttranslational arginine methylation occurs. We examined the subcellular localization of PABP2 in muscle specimens from five patients with OPMD, 14 patients with various neuromuscular disorders, and three normal controls. All Japanese patients with OPMD have been shown to have expanded (GCG)(8, 9, or 11) mutations in PABP2, as well as intranuclear tubulofilamentous inclusions (ITFI) of 8.5 nm. None of 50 separate Japanese control individuals were shown to have expanded (GCG) repeat in PABP2. Positive immunoreaction for polyclonal PABP2 was confined to the intranuclear aggregates of muscle fibers exclusively in patients with OPMD. Frequency of the nuclei positive for PABP2 (2%) was similar to that of ITFI detected by electron microscopy (2.5%). There was no apparent relationship between the frequency of PABP2-positive intranuclear aggregates and the severity of muscle fiber damage. In contrast, nuclear immunoreaction was not detected in any samples from normal controls or from other neuromuscular diseases. These results suggest the presence of molecular modification of the product of expanded (GCG) repeat in PABP2, since the synthetic antigen peptide may not recognize a highly dimethylated cluster of arginine residues of the native PABP2, but may recognize the mutated form. Nuclear accumulation of expanded PABP2 product implies a causative role for ITFI.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12747745"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11003790"
},
{
- "id": "pmid:12090474",
+ "id": "pmid:10734263",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/12090474",
- "title": "Non-glycosylated tandem repeats of MUC1 facilitate attachment of breast tumor cells to normal human lung tissue and immobilized extracellular matrix proteins (ECM) in vitro: potential role in metastasis.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/10734263",
+ "title": "Oculopharyngeal muscular dystrophy in a Japanese family with a short GCG expansion (GCG)(11) in PABP2 gene.",
"type": "article-journal",
- "doi": "10.1023/a:1015590515957",
+ "doi": "10.1016/s0960-8966(99)00104-2",
"authors": [
- ["Pawel", "Ciborowski"],
- ["Olivera J", "Finn"]
+ ["T", "Nagashima"],
+ ["H", "Kato"],
+ ["M", "Kase"],
+ ["S", "Maguchi"],
+ ["Y", "Mizutani"],
+ ["K", "Matsuda"],
+ ["T", "Chuma"],
+ ["Y", "Mano"],
+ ["Y", "Goto"],
+ ["N", "Minami"],
+ ["I", "Nonaka"],
+ ["K", "Nagashima"]
],
- "publisher": "Clinical & experimental metastasis",
- "issn": "0262-0898",
- "date": "2002-01-01",
- "abstract": "MUC1 is a transmembrane glycoprotein abundantly expressed on the apical surface of human ductal epithelial cells and over entire cell surface of tumors originating from those cells. It is 300 to 500 nm long and has a rigid, rod-like structure protruding from the cell surface. MUC1 expressed by normal cells has heavily O-glycosylated tandem repeat domain while MUC1 on malignant cells is aberrantly O-glycosylated. Substantially reduced (aberrant) glycosylation of the tandem repeat region of tumor MUC1 results in uncovering of the polypeptide core. This new structural feature may play an important role in the attachment of metastasizing tumor cells to tissues at distant sites. We show that MDA-MB-231 cells attaching to the immobilized extracellular matrix proteins (ECM) are higher MUC1 expressers than those non-attaching and that the attachment is inhibited by the addition of non-glycosylated, MUC1 peptide. This 100 a.a. peptide composed of 5 tandem repeats from the tandem repeat domain mimics the forms of MUC1 found in ascites fluid of cancer patients. We also show that this synthetic form of MUC1 inhibited attachment of breast tumor cells to sections of normal human lung tissue and immobilized ECM. We did not find correlation between the expression of Tn (GalNAc-Ser/Thr) epitope and the ability of tumor cells to adhere to the immobilized ECM. These results indicate that the non-glycosylated form of MUC1 plays a role in the initial attachment of carcinoma cells to tissues at distant sites, which may facilitate establishment of metastatic foci.",
+ "publisher": "Neuromuscular disorders : NMD",
+ "issn": "0960-8966",
+ "date": "2000-03-01",
+ "abstract": "Clinicopathological and molecular genetic findings on a new Japanese family with oculopharyngeal muscular dystrophy are reported. The family has 54 members, ten of whom are affected (seven male and three female), in 3 generations. Three affected males, one affected female and one unaffected female of seven living siblings in the third generation were examined. Bilateral ptosis developed in the 4th and 5th decades in the three male cases, and in the 7th decade in the female, and this was followed by diplopia, nasal voice, dysphagia and muscle weakness. In addition, severe external ophthalmoplegia, dysphonia, and proximal amyotrophy were prominent in this family. Electromyographs revealed myogenic/neurogenic changes, and computed tomography disclosed selective muscle wasting with fatty replacement, predominantly in the lower extremities. Muscle biopsy in the four affected patients showed variation in fiber size, and the presence of small angulated fibers and occasional rimmed vacuoles. Electron microscopic examination revealed an accumulation of filamentous inclusions in muscle fiber nuclei. DNA analysis identified that (GCG)(6) in the PABP2 gene was expanded to (GCG)(11) in the four affected cases examined. All studies were negative in the one unaffected. These results confirm that OPMD is caused by GCG short expansion and provides insights into the genetic mechanisms which may contribute to adult onset myopathy, confined to oculopharyngeal muscles.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12090474"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10734263"
},
{
- "id": "pmid:11445551",
+ "id": "pmid:38454954",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/11445551",
- "title": "In vivo glycosylation of mucin tandem repeats.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38454954",
+ "title": "Pulmonary hypertension in an adult patient with congenital central hypoventilation syndrome: a case report.",
"type": "article-journal",
- "doi": "10.1093/glycob/11.6.459",
+ "doi": "10.1093/ehjcr/ytae109",
"authors": [
- ["H S", "Silverman"],
- ["S", "Parry"],
- ["M", "Sutton-Smith"],
- ["M D", "Burdick"],
- ["K", "McDermott"],
- ["C J", "Reid"],
- ["S K", "Batra"],
- ["H R", "Morris"],
- ["M A", "Hollingsworth"],
- ["A", "Dell"],
- ["A", "Harris"]
+ ["Yosuke", "Terui"],
+ ["Shoko", "Ohura"],
+ ["Tetsuji", "Nozaki"],
+ ["Takuya", "Yagi"]
],
- "publisher": "Glycobiology",
- "issn": "0959-6658",
- "date": "2001-06-01",
- "abstract": "The biochemical and biophysical properties of mucins are largely determined by extensive O-glycosylation of serine- and threonine-rich tandem repeat (TR) domains. In a number of human diseases aberrant O-glycosylation is associated with variations in the properties of the cell surface-associated and secreted mucins. To evaluate in vivo the O-glycosylation of mucin TR domains, we generated recombinant chimeric mucins with TR sequences from MUC2, MUC4, MUC5AC, or MUC5B, which were substituted for the native TRs of epitope-tagged MUC1 protein (MUC1F). These hybrid mucins were extensively O-glycosylated and showed the expected association with the cell surface and release into culture media. The presence of different TR domains within the chimeric mucins appears to have limited influence on their posttranslational processing. Alterations in glycosylation were detailed by fast atom bombardment mass spectrometry and reactivity with antibodies against particular blood-group and tumor-associated carbohydrate antigens. Future applications of these chimeras will include investigations of mucin posttranslational modification in the context of disease.",
+ "publisher": "European heart journal. Case reports",
+ "issn": "2514-2119",
+ "date": "2024-02-26",
+ "abstract": "Congenital central hypoventilation syndrome (CCHS) is a life-threatening disorder of autonomic respiratory control. Mutations in the paired-like homeobox 2B (PHOX2B) gene impair respiratory drive, causing hypercarbia and hypoxaemia. Most patients with CCHS are diagnosed in the neonatal period; however, a few are diagnosed in adulthood.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11445551"
-},
-{
- "id": "pmid:11391628",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/11391628",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:11391628']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38454954"
},
{
- "id": "pmid:11169964",
+ "id": "pmid:38431667",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/11169964",
- "title": "Identification of three non-VNTR MUC1-derived HLA-A*0201-restricted T-cell epitopes that induce protective anti-tumor immunity in HLA-A2/K(b)-transgenic mice.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38431667",
+ "title": "Alternative low-populated conformations prompt phase transitions in polyalanine repeat expansions.",
"type": "article-journal",
- "doi": "10.1002/1097-0215(200002)9999:9999<::aid-ijc1051>3.0.co;2-z",
+ "doi": "10.1038/s41467-024-46236-5",
"authors": [
- ["L C", "Heukamp"],
- ["S H", "van der Burg"],
- ["J W", "Drijfhout"],
- ["C J", "Melief"],
- ["J", "Taylor-Papadimitriou"],
- ["R", "Offringa"]
+ ["Rosa", "Ant\u00f3n"],
+ ["Miguel \u00c1", "Trevi\u00f1o"],
+ ["David", "Pantoja-Uceda"],
+ ["Sara", "F\u00e9lix"],
+ ["Mar\u00eda", "Babu"],
+ ["Eurico J", "Cabrita"],
+ ["Markus", "Zweckstetter"],
+ ["Philip", "Tinnefeld"],
+ ["Andr\u00e9s M", "Vera"],
+ ["Javier", "Oroz"]
],
- "publisher": "International journal of cancer",
- "issn": "0020-7136",
- "date": "2001-02-01",
- "abstract": "The human epithelial mucin MUC1 is over-expressed in more than 90% of carcinomas of the breast, ovary, and pancreas as well as in some other tumours, making it a potential target for tumour immunotherapy. We have identified several MUC1-derived peptides mapping outside the variable number tandem repeat region that comply with the peptide-binding motif for HLA-A*0201 and that become processed into stable major histocompatibility complex-peptide complexes as assessed by in vitro assays. In A2/K(b) transgenic mice, 3 peptides, namely MUC(79-87) (TLAPATEPA), MUC(167-175) (ALGSTAPPV) and MUC(264-272) (FLSFHISNL) elicit peptide-specific cytotoxic T lymphocyte (CTL) immunity, which protects these mice against a challenge with MUC1, A2/K(b)-expressing tumour cells. These peptides therefore represent naturally processed MUC1-derived CTL epitopes that could be used as components in peptide-based vaccines and for the analysis of anti-MUC1 CTL responses in A*0201-positive patients with MUC1-expressing tumours.",
+ "publisher": "Nature communications",
+ "issn": "2041-1723",
+ "date": "2024-03-02",
+ "abstract": "Abnormal trinucleotide repeat expansions alter protein conformation causing malfunction and contribute to a significant number of incurable human diseases. Scarce structural insights available on disease-related homorepeat expansions hinder the design of effective therapeutics. Here, we present the dynamic structure of human PHOX2B C-terminal fragment, which contains the longest polyalanine segment known in mammals. The major \u03b1-helical conformation of the polyalanine tract is solely extended by polyalanine expansions in PHOX2B, which are responsible for most congenital central hypoventilation syndrome cases. However, polyalanine expansions in PHOX2B additionally promote nascent homorepeat conformations that trigger length-dependent phase transitions into solid condensates that capture wild-type PHOX2B. Remarkably, HSP70 and HSP90 chaperones specifically seize PHOX2B alternative conformations preventing phase transitions. The precise observation of emerging polymorphs in expanded PHOX2B postulates unbalanced phase transitions as distinct pathophysiological mechanisms in homorepeat expansion diseases, paving the way towards the search of therapeutics modulating biomolecular condensates in central hypoventilation syndrome.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11169964"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38431667"
},
{
- "id": "pmid:10741704",
+ "id": "pmid:38001308",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/10741704",
- "title": "Flow cytometric measurement of intracellular cytokines detects immune responses in MUC1 immunotherapy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38001308",
+ "title": "Characteristics and outcomes in children with congenital central hypoventilation syndrome on long-term mechanical ventilation in the Netherlands.",
"type": "article-journal",
- "doi": "",
+ "doi": "10.1007/s00431-023-05339-9",
"authors": [
- ["V", "Karanikas"],
- ["J", "Lodding"],
- ["V C", "Maino"],
- ["I F", "McKenzie"]
+ ["E E", "Evers-Bikker"],
+ ["W", "de Weerd"],
+ ["P J", "Wijkstra"],
+ ["L", "Corel"],
+ ["L P", "Verweij"],
+ ["B A H", "Vosse"]
],
- "publisher": "Clinical cancer research : an official journal of the American Association for Cancer Research",
- "issn": "1078-0432",
- "date": "2000-03-01",
- "abstract": "The detection of tumor-specific T cells in immunized cancer patients usually relies on lengthy and difficult CTL assays; we now report on flow cytometry to detect the intracellular cytokines interleukin 2 (IL-2), IL-4, IFN-gamma, and tumor necrosis factor alpha (TNF-alpha) produced by CD4+CD69+ and CD8+CD69+ activated T cells after MUC1 antigen stimulation. Peripheral blood mononuclear cells were obtained from 12 patients with adenocarcinoma injected with mannan-MUC1; cells were exposed in vitro for 18 h to MUCI peptide in the presence of CD28 monoclonal antibody and Brefeldin; permeabilized cells were used for the expression of cytokines. After stimulation in vitro with MUC1-variable number of tandem repeats peptides, CD8+CD69+ T cells from all immunized patients generated 3-9 times higher levels of TNF-alpha(P < 0.038) and IFN-gamma (P <0.010) than did cells from 12 normal subjects; minor increases in IL-4 occurred. By contrast, CD4+CD69+ cells showed no overall alteration in TNF-alpha and IFN-gamma cytokine production, although in some patients, their measurement was informative; the measurement of IL-2 was not useful in either CD4+CD69+ or CD8+CD69+ cells. We conclude that in MUC1-immunized patients, the measurement of TNF-alpha and IFN-gamma in activated CD69+CD8+ T cells may be indicative of their immune status.",
+ "publisher": "European journal of pediatrics",
+ "issn": "1432-1076",
+ "date": "2023-11-25",
+ "abstract": "Congenital central hypoventilation syndrome (CCHS) is a rare condition characterized by central hypoventilation, leading to the majority of patients being dependent on ventilatory support during sleep. This condition is often accompanied by various associated symptoms, due to a PHOX2B gene variant involved in neuronal crest cell migration. This study is the first to review the characteristics and outcomes in children with CCHS on long-term mechanical ventilation in the Netherlands. We performed a retrospective study of all CCHS patients treated in the 4 Centers of Home Mechanical Ventilation of the University Medical Centers in the Netherlands from 2000 till 2022 by collecting information from the electronic medical records, documented during follow-up. We included 31 patients, out of which 27 exhibited a known genetic profile associated with CCHS, while no PHOX2B variant was identified in the remaining patients. Among the 27 patients with known genetic profiles, 10 patients had a non-polyalanine repeat expansion mutation (NPARM), followed by 20/27, 20/25, and 20/26 polyalanine repeat expansion mutations (PARMs) in descending order. The most common presentation involved respiratory failure or apneas during the neonatal period with an inability to wean off ventilation. The majority of patients required ventilatory support during sleep, with four patients experiencing life-threatening events related to this dependency. Daily use of ventilatory support varied among different genetic profiles. All genotypes reported comorbidities, with Hirschsprung's disease and cardiac arrhythmias being the most reported comorbidities. Notably, Hirschprung's disease was exclusively observed in patients with a 20/27 PHOX2B variant.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10741704"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38001308"
},
{
- "id": "pmid:10653872",
+ "id": "pmid:33958749",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/10653872",
- "title": "Survival in early breast cancer patients is favorably influenced by a natural humoral immune response to polymorphic epithelial mucin.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/33958749",
+ "title": "Paired-like homeobox gene (PHOX2B) nonpolyalanine repeat expansion mutations (NPARMs): genotype-phenotype correlation in congenital central hypoventilation syndrome (CCHS).",
"type": "article-journal",
- "doi": "10.1200/jco.2000.18.3.574",
+ "doi": "10.1038/s41436-021-01178-x",
"authors": [
- ["S", "von Mensdorff-Pouilly"],
- ["A A", "Verstraeten"],
- ["P", "Kenemans"],
- ["F G", "Snijdewint"],
- ["A", "Kok"],
- ["G J", "Van Kamp"],
- ["M A", "Paul"],
- ["P J", "Van Diest"],
- ["S", "Meijer"],
- ["J", "Hilgers"]
+ ["Amy", "Zhou"],
+ ["Casey M", "Rand"],
+ ["Sara M", "Hockney"],
+ ["Grace", "Niewijk"],
+ ["Patrick", "Reineke"],
+ ["Virginia", "Speare"],
+ ["Elizabeth M", "Berry-Kravis"],
+ ["Lili", "Zhou"],
+ ["Lawrence J", "Jennings"],
+ ["Min", "Yu"],
+ ["Isabella", "Ceccherini"],
+ ["Tiziana", "Bachetti"],
+ ["Melanie", "Pennock"],
+ ["Kai Lee", "Yap"],
+ ["Debra E", "Weese-Mayer"]
],
- "publisher": "Journal of clinical oncology : official journal of the American Society of Clinical Oncology",
- "issn": "0732-183X",
- "date": "2000-02-01",
- "abstract": "Polymorphic epithelial mucin (PEM or MUC1) is being studied as a vaccine substrate for the immunotherapy of patients with adenocarcinoma. The present study analyzes the incidence of naturally occurring MUC1 antibodies in early breast cancer patients and relates the presence of these antibodies in pretreatment serum to outcome of disease.",
+ "publisher": "Genetics in medicine : official journal of the American College of Medical Genetics",
+ "issn": "1530-0366",
+ "date": "2021-05-06",
+ "abstract": "CCHS is an extremely rare congenital disorder requiring artificial ventilation as life support. Typically caused by heterozygous polyalanine repeat expansion mutations (PARMs) in the PHOX2B gene, identification of a relationship between PARM length and phenotype severity has enabled anticipatory management. However, for patients with non-PARMs in PHOX2B (NPARMs, ~10% of CCHS patients), a genotype-phenotype correlation has not been established. This comprehensive report of PHOX2B NPARMs and associated phenotypes, aims at elucidating potential genotype-phenotype correlations that will guide anticipatory management.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10653872"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33958749"
},
{
- "id": "pmid:10430099",
+ "id": "pmid:33855005",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/10430099",
- "title": "Immunization of chimpanzees with tumor antigen MUC1 mucin tandem repeat peptide elicits both helper and cytotoxic T-cell responses.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/33855005",
+ "title": "How the Management of Children With Congenital Central Hypoventilation Syndrome Has Changed Over Time: Two Decades of Experience From an Italian Center.",
"type": "article-journal",
- "doi": "",
+ "doi": "10.3389/fped.2021.648927",
"authors": [
- ["S M", "Barratt-Boyes"],
- ["A", "Vlad"],
- ["O J", "Finn"]
+ ["Federica", "Porcaro"],
+ ["Maria Giovanna", "Paglietti"],
+ ["Claudio", "Cherchi"],
+ ["Alessandra", "Schiavino"],
+ ["Maria Beatrice", "Chiarini Testa"],
+ ["Renato", "Cutrera"]
],
- "publisher": "Clinical cancer research : an official journal of the American Association for Cancer Research",
- "issn": "1078-0432",
- "date": "1999-07-01",
- "abstract": "CTLs and antibody responses to the tumor-associated antigen MUC1 mucin can be detected in patients with adenocarcinomas of the breast, pancreas, colon, and ovary. However, neither response is generally effective at controlling disease. Methods to augment immunity to MUC1 are being designed, with the expectation that this will lead to an antitumor response. The key to eliciting potent immunity to tumor MUC1 may be in generating MUC1-specific T-helper cell responses, which, to date, have not been reported in cancer patients. We have recently demonstrated that a synthetic vaccine representing five copies of the MUC1 tandem repeat peptide can be used to prime MUC1-specific human CD4+ T cells in vitro. Here, we extend these studies to test the immunogenicity and safety of the tandem repeat peptide in the chimpanzee, which has the identical MUC1 tandem repeat sequence to the human. To promote induction of Th1-type responses, we used the novel adjuvant LeIF, a Leishmania-derived protein that is known to stimulate human peripheral blood mononuclear cells (PBMCs) and antigen-presenting cells, to produce a Th1-type cytokine profile. We found that MUC1 tandem repeat peptide administered with LeIF elicited positive, albeit transient, proliferative T-cell responses to MUC1 in the PBMCs from four of four chimpanzees. Immunization induced MUC1-specific IFN-gamma but not interleukin 4 expression in CD4+ T cells from PBMCs and draining lymph nodes. MUC1-specific CTLs were also generated that did not induce detectable autoimmune dysfunction during the 1 year of observation. We conclude that the MUC1 tandem repeat peptide can be used to elicit both T-helper and cytotoxic cell responses to MUC1 in the primate and holds promise as a safe and effective cancer vaccine.",
+ "publisher": "Frontiers in pediatrics",
+ "issn": "2296-2360",
+ "date": "2021-03-29",
+ "abstract": "",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10430099"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33855005"
},
{
- "id": "pmid:10383817",
+ "id": "pmid:30786110",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/10383817",
- "title": "Presentation of MUC1 tumor antigen by class I MHC and CTL function correlate with the glycosylation state of the protein taken Up by dendritic cells.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30786110",
+ "title": "Novel PHOX2B mutations in congenital central hypoventilation syndrome.",
"type": "article-journal",
- "doi": "10.1006/cimm.1999.1512",
+ "doi": "10.1111/ped.13812",
"authors": [
- ["E M", "Hiltbold"],
- ["M D", "Alter"],
- ["P", "Ciborowski"],
- ["O J", "Finn"]
+ ["Ayako", "Sasaki"],
+ ["Yumiko", "Kishikawa"],
+ ["Reisuke", "Imaji"],
+ ["Yu", "Fukushima"],
+ ["Yukiko", "Nakamura"],
+ ["Yutaka", "Nishimura"],
+ ["Megumi", "Yamada"],
+ ["Yoichi", "Mino"],
+ ["Tetsuo", "Mitsui"],
+ ["Kiyoshi", "Hayasaka"]
],
- "publisher": "Cellular immunology",
- "issn": "0008-8749",
- "date": "1999-06-15",
- "abstract": "We previously reported that the glycosylated MUC1 tumor antigen circulating as soluble protein in patients' serum is not processed by dendritic cells and does not elicit MHC-Class II-restricted T helper responses in vitro. In contrast, a long synthetic peptide from the MUC1 tandem repeat region is presented by Class II molecules, resulting in the initiation of T helper cell responses. Here we addressed the ability of dendritic cells to present various glycosylated or not glycosylated forms of MUC1 by MHC Class I. We found that three different forms of MUC1, ranging from glycosylated and underglycosylated protein to unglycosylated synthetic peptide, were able to elicit MUC1-specific, Class-I-restricted CTL responses. The efficiency of processing and the resulting strength of CTL activity were inversely correlated with the degree of glycosylation of the antigen. Furthermore, the more efficiently processed 100mer peptide primed a broader repertoire of CTL than the glycosylated protein.",
+ "publisher": "Pediatrics international : official journal of the Japan Pediatric Society",
+ "issn": "1442-200X",
+ "date": "2019-04-17",
+ "abstract": "Congenital central hypoventilation syndrome (CCHS) is caused by mutation of paird-like homeobox 2B (PHOX2B). Approximately 90% of patients were found to carry polyalanine repeat expansion mutation (PARM), and the remaining 10% had non-PARM (NPARM). In PARM, the length of the polyalanine expansion correlates with clinical disease severity. Most patients with NPARM have hypoventilation symptoms in the neonatal period and complications of Hirschsprung disease, dysregulation of autonomic nervous system, and tumors of neural crest origin. Data on the genotype-phenotype association may contribute to the clinical management of the disease.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10383817"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30786110"
},
{
- "id": "pmid:10235488",
+ "id": "pmid:30672101",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/10235488",
- "title": "Cellular and humoral immune responses to MUC1 mucin and tandem-repeat peptides in ovarian cancer patients and controls.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30672101",
+ "title": "Congenital central hypoventilation syndrome: Severe disease caused by co-occurrence of two PHOX2B variants inherited separately from asymptomatic family members.",
"type": "article-journal",
- "doi": "10.1007/s002620050547",
+ "doi": "10.1002/ajmg.a.61047",
"authors": [
- ["F G", "Snijdewint"],
- ["S", "von Mensdorff-Pouilly"],
- ["A H", "Karuntu-Wanamarta"],
- ["A A", "Verstraeten"],
- ["I", "van Zanten-Przybysz"],
- ["P", "Hummel"],
- ["H W", "Nijman"],
- ["P", "Kenemans"],
- ["J", "Hilgers"]
+ ["Yakov", "Sivan"],
+ ["Amy", "Zhou"],
+ ["Lawrence J", "Jennings"],
+ ["Elizabeth M", "Berry-Kravis"],
+ ["Min", "Yu"],
+ ["Lili", "Zhou"],
+ ["Casey M", "Rand"],
+ ["Debra E", "Weese-Mayer"]
],
- "publisher": "Cancer immunology, immunotherapy : CII",
- "issn": "0340-7004",
- "date": "1999-04-01",
- "abstract": "The objective of this study was to demonstrate the presence of proliferative T cell responses to human polymorphic epithelial mucin (MUC1) and its tandem-repeat peptides in peripheral blood mononuclear cells (PBMC) from ovarian cancer patients and from controls and to correlate these cellular responses to a humoral response to MUC1. PBMC were obtained from 6 healthy women, from 13 women in the third trimester of pregnancy and from 21 ovarian cancer patients. Only 1 of the 6 healthy women showed a weak primary proliferative response (stimulation index, SI <2) to a 20-mer MUC1 tandem-repeat peptide in the presence of interleukin-2 (IL-2). In PBMC from 5/13 pregnant women (38%) a weak response could be induced by the 20-mer and/or 60-mer tandem-repeat peptides (SI < or =3.0) and in PBMC from 8/15 ovarian cancer patients (53%) 20-mer and/or 60-mer MUC1 tandem-repeat peptides induced primary responses (SI < or =5.4). MUC1 mucin purified from a breast tumor cell line and/or from urine of a healthy donor had a relatively strong stimulating effect (SI < or =19) on PBMC from 4 of 16 ovarian cancer patients (25%). In contrast, in PBMC of 9 ovarian cancer patients stimulated by the addition of a Candida albicans extract, MUC1 mucin strongly inhibited proliferation. This inhibition could partially be abrogated by the addition of IL-2. MUC1 (CA 15.3 assay) and free circulating MUC1 IgG and IgM antibodies (PEM.CIg assay) were determined in the plasma of all subjects. The MUC1 and the free circulating MUC1 IgG antibody plasma levels were significantly higher in the ovarian cancer patients than in the healthy women. Although no significant correlations were found between MUC1 mucin, MUC1 Ab plasma levels and the individual proliferative responses to the MUC1 antigens, an association may exist between them, since all three are significantly higher in the ovarian cancer patients than in the healthy women.",
+ "publisher": "American journal of medical genetics. Part A",
+ "issn": "1552-4833",
+ "date": "2019-01-23",
+ "abstract": "Congenital Central Hypoventilation Syndrome (CCHS) is a rare disease characterized by autonomic nervous system dysregulation. Central hypoventilation is the most prominent and clinically important presentation. CCHS is caused by mutations in paired-like homeobox 2b (PHOX2B) and is inherited in an autosomal dominant pattern. A co-occurrence of two asymptomatic PHOX2B variants with a classical CCHS presentation highlights the importance of clinical PHOX2B testing in parents and family members of all CCHS probands. Despite being an autosomal dominant disease, once a polyalanine repeat expansion mutation has been identified, sequencing of the other allele should also be considered.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10235488"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30672101"
},
{
- "id": "pmid:10022471",
+ "id": "pmid:30227298",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/10022471",
- "title": "Isolation of MUC1-primed B lymphocytes from tumour-draining lymph nodes by immunomagnetic beads.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30227298",
+ "title": "A novel PHOX2B gene mutation in an extremely low birth weight infant with congenital central hypoventilation syndrome and variant Hirschsprung's disease.",
"type": "article-journal",
- "doi": "10.1007/s002620050531",
+ "doi": "10.1016/j.ejmg.2018.09.008",
"authors": [
- ["C", "Petrarca"],
- ["B", "Casalino"],
- ["S", "von Mensdorff-Pouilly"],
- ["A", "Rughetti"],
- ["H", "Rahimi"],
- ["G", "Scambia"],
- ["J", "Hilgers"],
- ["L", "Frati"],
- ["M", "Nuti"]
+ ["Yuichiro", "Miura"],
+ ["Tatsuya", "Watanabe"],
+ ["Toshihiko", "Uchida"],
+ ["Tatsuro", "Nawa"],
+ ["Naobumi", "Endo"],
+ ["Taichi", "Fukuzawa"],
+ ["Ryuji", "Ohkubo"],
+ ["Junji", "Takeyama"],
+ ["Ayako", "Sasaki"],
+ ["Kiyoshi", "Hayasaka"]
],
- "publisher": "Cancer immunology, immunotherapy : CII",
- "issn": "0340-7004",
- "date": "1999-01-01",
- "abstract": "The humoral immune response against a tumour-associated antigen, polymorphic epithelial mucin (PEM, MUC1) in cancer patients was studied by isolating specific B cells primed for the antigen. Human B lymphocytes from tumour-draining lymph nodes, obtained from 12 patients with epithelial cancers, were immunoselected with magnetic beads coated with a 60mer synthetic peptide corresponding to three tandem repeats of the protein core of the MUC1 antigen. Short-term cultures of B cells were established utilizing interleukin-10 (IL-10), IL-4 and monoclonal antibody anti-CD40, and were maintained for a maximum of 3 weeks. B cell culture supernatants contained human anti-MUC1 antibodies, as detected by enzyme-linked immunosorbent assay, in 6/12 of the patients tested. Five of these patients, all with early-stage cancer, also had high levels of circulating anti-MUC1 IgM antibodies in the serum. A significant correlation was found (two-tailed P = 0.041) between the presence of circulating anti-MUC1 antibodies and the ability to isolate PEM-specific B cells from tumour-draining lymph nodes. The technique proposed provides a useful method for the analysis of natural immunity against defined tumour antigens.",
+ "publisher": "European journal of medical genetics",
+ "issn": "1878-0849",
+ "date": "2018-09-15",
+ "abstract": "Congenital central hypoventilation syndrome is a disorder of respiratory control caused by mutations in the paired-like homeobox 2B gene. Mutations in the paired-like homeobox 2B gene are also responsible for Hirschsprung's disease. Variant Hirschsprung's disease is a rarer disorder that does not meet the diagnostic criteria of Hirschsprung's disease, although severe functional bowel obstruction persists. We present a case of an extremely low birth weight infant with congenital central hypoventilation syndrome and variant Hirschsprung's disease. A male infant who was diagnosed to have fetal growth restriction and polyhydramnios was delivered by emergency cesarean section at 30 weeks and 3 days of gestational age due to non-reassuring fetal status. The birth weight was 979\u202fg, and intensive care was started immediately following delivery. The patient exhibited refractory apnea and was diagnosed with congenital central hypoventilation syndrome by genetic testing of the paired-like homeobox 2B gene. The patient also exhibited refractory functional bowel obstruction and was diagnosed to have variant Hirschsprung's disease through pathological examination of his intestinal specimens. The patient grew slowly but surely with intensive care including mechanical ventilation and parenteral nutrition. However, the patient repeatedly suffered from sepsis and died of fungemia at 197 days of age. This is the first congenital central hypoventilation syndrome case that was accompanied with variant Hirschsprung's disease, and the paired-like homeobox 2B mutation detected in this case (NM_003924.3: c.441G\u202f>\u202fC; p.(Gln147His)) is novel. This case suggests that the paired-like homeobox 2B mutation causes not only congenital central hypoventilation syndrome and Hirschsprung's disease, but also variant Hirschsprung's disease in humans. It also highlights the extreme difficulty in treating premature infants with severe and prolonged functional bowel obstruction.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10022471"
-},
-{
- "id": "pmid:9823312",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/9823312",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:9823312']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30227298"
},
{
- "id": "pmid:9755875",
+ "id": "pmid:27129232",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/9755875",
- "title": "Induction of HLA-unrestricted and HLA-class-II-restricted cytotoxic T lymphocytes against MUC-1 from patients with colorectal carcinomas using recombinant MUC-1 vaccinia virus.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27129232",
+ "title": "Alanine Expansions Associated with Congenital Central Hypoventilation Syndrome Impair PHOX2B Homeodomain-mediated Dimerization and Nuclear Import.",
"type": "article-journal",
- "doi": "10.1007/s002620050500",
+ "doi": "10.1074/jbc.m115.679027",
"authors": [
- ["J", "Akagi"],
- ["K", "Nakagawa"],
- ["H", "Egami"],
- ["M", "Ogawa"]
+ ["Simona", "Di Lascio"],
+ ["Debora", "Belperio"],
+ ["Roberta", "Benfante"],
+ ["Diego", "Fornasari"]
],
- "publisher": "Cancer immunology, immunotherapy : CII",
- "issn": "0340-7004",
- "date": "1998-09-01",
- "abstract": "We recently reported that immunization with a recombinant MUC-1 vaccinia virus (rVMUC-1) protected C57BL/6 mice from challenge with DF3/MUC-1-positive syngeneic tumors. To elucidate whether anti-MUC-1 tumor immunity, especially MUC-1-specific cytotoxic T lymphocytes (CTI), can be induced in cancer patients by rVMUC-1, we stimulated the peripheral blood lymphocytes from patients with DF3/MUC-1+ or DF3/MUC-1 colon carcinomas using the autologous monocytes infected with rVMUC-1 (rVAMN). The stimulated T lymphocytes from two patients with DF3/MUC-1-positive colorectal carcinomas (rVPY+T and rVPW+T) demonstrated HLA-unrestricted cytotoxicity against MUC-1, whereas those from the patient with DF3/MUC-1-negative colon carcinoma (rVPA-T) did not. The HLA-unrestricted cytotoxicity was demonstrated by the CD8+ T cells possibly recognizing an epitope present on the tandem repeats. Adoptive immunotherapy who performed three times with patient PY, at 4-week intervals. The adoptive transfer of the first stimulated lymphocytes, demonstrating a high level of HLA-unrestricted cytotoxicity against MUC-1, resulted in the significant reduction of the liver metastasis of patient PY. However, HLA-unrestricted cytotoxicity against MUC-1 was extremely reduced at the second transfer and finally eliminated at the third, whereas the CD4+ T cells demonstrating HLA-class-II-restricted cytotoxicity against MUC-1 predominantly proliferated at the third adoptive immunotherapy treatment. The liver metastasis and the serum levels of tumor markers (carcinoembryonic antigen CA19-9) demonstrated a rapid and marked increment after the second transfer and especially after the third. These results suggest that the HLA-unrestricted cytotoxic CD8+ T cells against MUC-1, induced in patients with DF3/MUC-1+ colorectal carcinomas using rVMUC-1, correlate with the antitumor activity in vivo.",
+ "publisher": "The Journal of biological chemistry",
+ "issn": "1083-351X",
+ "date": "2016-04-27",
+ "abstract": "Heterozygous mutations of the human PHOX2B gene, a key regulator of autonomic nervous system development, lead to congenital central hypoventilation syndrome (CCHS), a neurodevelopmental disorder characterized by a failure in the autonomic control of breathing. Polyalanine expansions in the 20-residues region of the C terminus of PHOX2B are the major mutations responsible for CCHS. Elongation of the alanine stretch in PHOX2B leads to a protein with altered DNA binding, transcriptional activity, and nuclear localization and the possible formation of cytoplasmic aggregates; furthermore, the findings of various studies support the idea that CCHS is not due to a pure loss of function mechanism but also involves a dominant negative effect and/or toxic gain of function for PHOX2B mutations. Because PHOX2B forms homodimers and heterodimers with its paralogue PHOX2A in vitro, we tested the hypothesis that the dominant negative effects of the mutated proteins are due to non-functional interactions with the wild-type protein or PHOX2A using a co-immunoprecipitation assay and the mammalian two-hybrid system. Our findings show that PHOX2B forms homodimers and heterodimerizes weakly with mutated proteins, exclude the direct involvement of the polyalanine tract in dimer formation, and indicate that mutated proteins retain partial ability to form heterodimers with PHOX2A. Moreover, in this study, we investigated the effects of the longest polyalanine expansions on the homeodomain-mediated nuclear import, and our data clearly show that the expanded C terminus interferes with this process. These results provide novel insights into the effects of the alanine tract expansion on PHOX2B folding and activity.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9755875"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27129232"
},
{
- "id": "pmid:9591045",
+ "id": "pmid:26063465",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/9591045",
- "title": "An enzyme-linked immunosorbent assay for the measurement of circulating antibodies to polymorphic epithelial mucin (MUC1).",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26063465",
+ "title": "Genotype-phenotype relationship in Japanese patients with congenital central hypoventilation syndrome.",
"type": "article-journal",
- "doi": "10.1159/000030006",
+ "doi": "10.1038/jhg.2015.65",
"authors": [
- ["S", "von Mensdorff-Pouilly"],
- ["M M", "Gourevitch"],
- ["P", "Kenemans"],
- ["A A", "Verstraeten"],
- ["G J", "van Kamp"],
- ["A", "Kok"],
- ["K", "van Uffelen"],
- ["F G", "Snijdewint"],
- ["M A", "Paul"],
- ["S", "Meijer"],
- ["J", "Hilgers"]
+ ["Tomoyuki", "Shimokaze"],
+ ["Ayako", "Sasaki"],
+ ["Toru", "Meguro"],
+ ["Hisaya", "Hasegawa"],
+ ["Yuka", "Hiraku"],
+ ["Tetsushi", "Yoshikawa"],
+ ["Yumiko", "Kishikawa"],
+ ["Kiyoshi", "Hayasaka"]
],
- "publisher": "Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine",
- "issn": "1010-4283",
- "date": "1998-01-01",
- "abstract": "About one-third of breast and ovarian carcinoma patients have circulating antibodies reactive with polymorphic epithelial mucin (MUC1), either free or bound to immune complexes. While the presence of these immune complexes has prognostic significance in breast cancer patients, the significance of free MUC1 antibodies is less clear. The objective of this study was to develop a reliable assay for the accurate determination of circulating free antibodies to MUC1.",
+ "publisher": "Journal of human genetics",
+ "issn": "1435-232X",
+ "date": "2015-06-11",
+ "abstract": "Examine the genotype-phenotype relationship in Japanese congenital central hypoventilation syndrome (CCHS) patients and estimate the incidence of CCHS in Japan. Subjects were 92 Japanese patients with PHOX2B mutations; 19 cases carried 25 polyalanine repeat expansion mutations (PARMs); 67 cases carried 26 or more PARMs; and 6 had non-PARMs (NPARMs). We collected clinical data in all patients and estimated the development or intelligent quotients only in the patients carrying 25 PARM. The estimated incidence of CCHS was greater than one case per 148\u2009000 births. Polyhydramnios was observed in three cases. Twelve infants exhibited depressed respiration at birth. In 19 cases carrying 25 PARM, the male-to-female ratio was ~3, no cases had Hirschsprung disease; 7 cases (37%) developed hypoventilation after the neonatal period, and 8 cases (42%) had mental retardation. In other 73 cases carrying 26 or more PARMs or NPARMs, male-to-female ratio was equal; patients frequently complicated with Hirschsprung disease and constipation, and all patients presented with hypoventilation in the neonatal period. Clinical symptoms were severe in most patients carrying long PARMs and NPARMs. In 25 PARM, additional genetic and/or epigenetic factors were required for CCHS development and male sex is likely a predisposing factor. The patients carrying 25 PARM frequently had mental retardation likely because they were not able to receive appropriate ventilation support following a definitive diagnosis owing to subtle and or irregular hypoventilation. Molecular diagnosis provides a definitive diagnosis and enables to receive appropriate ventilator support.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9591045"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26063465"
},
{
- "id": "pmid:9575675",
+ "id": "pmid:24135798",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/9575675",
- "title": "A large number of tandem repeats in the polymorphic epithelial mucin gene is associated with severe acne.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/24135798",
+ "title": "An unusual cause of fetal hypomobility:congenital central hypoventilation syndrome associated with hirschsprung disease.",
"type": "article-journal",
- "doi": "10.1111/j.1346-8138.1998.tb02370.x",
+ "doi": "10.1007/s00431-013-2171-8",
"authors": [
- ["I", "Ando"],
- ["A", "Kukita"],
- ["G", "Soma"],
- ["H", "Hino"]
+ ["Sybille", "De Montpellier"],
+ ["Yves", "Sznajer"],
+ ["Jeanne", "Amiel"],
+ ["Genevieve", "Francois"],
+ ["Marie-Cecile", "Nassogne"],
+ ["Christian", "Debauche"],
+ ["Isabelle", "Scheers"]
],
- "publisher": "The Journal of dermatology",
- "issn": "0385-2407",
- "date": "1998-03-01",
- "abstract": "Polymorphic epithelial mucin (PEM) or MUC1 is a glycoprotein secreted from various epithelial gland tissues. In skin, PEM is detected in sweat glands and sebaceous glands by the DF3 monoclonal antibody. The gene of PEM includes an allele exhibiting length polymorphism due to a variable number of tandem repeats (VNTR); this is expressed co-dominantly, which may influence the microenvironment of the skin. The allelic size variation of the PEM gene was investigated in Japanese acne patients, atopic dermatitis patients, and healthy controls. The frequency of longer length alleles was significantly higher in severe acne patients.",
+ "publisher": "European journal of pediatrics",
+ "issn": "1432-1076",
+ "date": "2013-10-18",
+ "abstract": "Co-occurrence of congenital central hypoventilation syndrome and Hirschsprung disease is known as Haddad syndrome. Affected patients develop with variable expressivity a dysfunction of the autonomic nervous system. We report the natural history of a full-term newborn infant presenting multiple features of autonomic system dysfunction that were already noted antenatally. The presence of a nonpolyalanine repeat expansion mutation in the PHOX2B gene confirmed postnatally the diagnosis of Haddad syndrome. This case suggests that patients presenting with autonomic system dysfunction may already present signs of the disease during the fetal period. Furthermore, antenatal presentations may correlate with a more severe presentation of the disease. In conclusion, antenatal signs of dysautonomy should stimulate multidisciplinary prenatal approach to orientate proper postnatal intervention and facilitate treatment strategies.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9575675"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24135798"
},
{
- "id": "pmid:9551361",
+ "id": "pmid:23460545",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/9551361",
- "title": "Cyclophosphamide enhances the CTL precursor frequency in mice immunized with MUC1-mannan fusion protein (M-FP).",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23460545",
+ "title": "Recurrence of CCHS associated PHOX2B poly-alanine expansion mutation due to maternal mosaicism.",
"type": "article-journal",
- "doi": "10.1097/00002371-199803000-00003",
+ "doi": "10.1002/ppul.22790",
"authors": [
- ["V", "Apostolopoulos"],
- ["V", "Popovski"],
- ["I F", "McKenzie"]
+ ["Tiziana", "Bachetti"],
+ ["Marco", "Di Duca"],
+ ["Matteo", "Della Monica"],
+ ["Lidia", "Grappone"],
+ ["Gioacchino", "Scarano"],
+ ["Isabella", "Ceccherini"]
],
- "publisher": "Journal of immunotherapy (Hagerstown, Md. : 1997)",
- "issn": "1524-9557",
- "date": "1998-03-01",
- "abstract": "We have previously described the induction of murine CD8+ major histocompatibility complex class I restricted cytotoxic T cells to the 20 amino acid repeat region of human Mucin 1 (MUC1) variable number of tandem repeats region--a mucin greatly increased in expression in breast cancer and proposed as a target for immunotherapy. Mannan-MUC1 immunization protocol induces a high cytotoxic T lymphocyte (CTL) frequency, and some protection of mice against a tumor challenge. The CTL frequency can be substantially increased using cyclophosphamide (Cy), from 1/84,900 without Cy to 1/8,100 with Cy. Furthermore, in the presence of Cy, established tumors are rapidly eradicated, which does not happen in its absence. Cy clearly gives a major increase in the frequency of CTL precursors (CTLp) to MUC1 and could be of therapeutic value in patients.",
+ "publisher": "Pediatric pulmonology",
+ "issn": "1099-0496",
+ "date": "2013-03-04",
+ "abstract": "Heterozygous in frame trinucleotide duplications within the PHOX2B gene, leading to poly-alanine expansions, cause Congenital Central Hypoventilation Syndrome. Here we report about a CCHS patient, carrying a +13Ala PHOX2B expansion, whose asymptomatic mother resulted with a low level of mosaicism for the same mutation in peripheral blood cells. Her second pregnancy ended with the spontaneous miscarriage of a fetus who had inherited the PHOX2B mutation, thus confirming germline mosaicism in the mother and the need of proper genetic counseling to CCHS families.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9551361"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23460545"
},
{
- "id": "pmid:8967520",
+ "id": "pmid:23460419",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/8967520",
- "title": "Regulation of MUC5 and MUC1 gene expression: correlation with airway mucous differentiation.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23460419",
+ "title": "Heterozygous 24-polyalanine repeats in the PHOX2B gene with different manifestations across three generations.",
"type": "article-journal",
- "doi": "10.1152/ajplung.1996.270.5.l846",
+ "doi": "10.1002/ppul.22731",
"authors": [
- ["K", "Guzman"],
- ["T", "Bader"],
- ["P", "Nettesheim"]
+ ["Piyaporn", "Chuen-im"],
+ ["Shinawi", "Marwan"],
+ ["Jodi", "Carter"],
+ ["James", "Kemp"],
+ ["Katherine", "Rivera-Spoljaric"]
],
- "publisher": "The American journal of physiology",
- "issn": "0002-9513",
- "date": "1996-05-01",
- "abstract": "The purpose of this paper was to obtain probes to study the structure and function of mucins in rat models of airway cell differentiation and disease. We report the isolation and characterization of the rat cDNA homologue of the human airway secretory mucin, MUC5. Furthermore, we demonstrate the coordinate regulation of the expression of MUC5 and MUC1 (a membrane-bound mucin) and mucous differentiation. The rat MUC5 was cloned by the RT-PCR using motifs conserved in the secretory mucins, MUC2 and MUC5. The rat cDNA revealed a high degree of sequence similarity to human MUC5 (73% at the amino acid level). Alignments with three other secretory mucins (human MUC5, human MUC2, rat MUC2), indicated a conservation of the cysteines and of the octapeptide motifs, but a lack of conservation of a short tandem repeat sequence that is found only in the human MUC5. Northern analysis of MUC1 and MUC5 indicated a specific tissue-restricted pattern of expression. Surprisingly, rat MUC5 exhibited a monodisperse signal, a characteristic that is unusual for most secretory mucins, including the human MUC5. Expression of MUC1 and MUC5 correlated with mucous differentiation. Both genes were expressed at undetectable or very low levels in undifferentiated cultures, but both mucins became strongly expressed during mucous differentiation. Furthermore, neither mucin gene was expressed in retinoid-deficient cultures that undergo squamous instead of mucous differentiation. These studies demonstrate that expression of MUC1 and MUC5 is coordinately regulated with airway mucous cell differentiation. These cDNAs should provide useful tools to study mucin synthesis during differentiation and disease.",
+ "publisher": "Pediatric pulmonology",
+ "issn": "1099-0496",
+ "date": "2013-03-04",
+ "abstract": "Congenital central hypoventilation syndrome (CCHS) is an uncommon genetic disorder that is characterized by alveolar hypoventilation and autonomic dysregulation. More than 90% of the patients are heterozygous for polyalanine repeat expansion mutations in the paired-like homeobox 2b (PHOX2B) gene. The normal genotype has a 20-polyalanine sequence whereas expanded alleles are usually 25-33. Heterozygous 24-polyalanine repeat expansion mutation in the PHOX2B gene has rarely been reported. We report three consecutive generations harboring heterozygous 24-polyalanine repeats in the PHOX2B gene with manifestations ranging from apparently asymptomatic to alveolar hypoventilation and apnea requiring mechanical ventilation. The 3-year-old proband developed cor pulmonale and central hypoventilation following an upper respiratory tract infection. Our findings add to the accumulating evidence that the 24-polyalanine repeat in the PHOX2B is a disease-causing mutation. In addition, a high index of suspicion and careful monitoring after anesthesia, sedation, or respiratory illnesses should be exercised when evaluating asymptomatic family members with this genotype.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8967520"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23460419"
},
{
- "id": "pmid:7594478",
+ "id": "pmid:22829249",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/7594478",
- "title": "Identification of an HLA-A11-restricted epitope from the tandem repeat domain of the epithelial tumor antigen mucin.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22829249",
+ "title": "Congenital central hypoventilation syndrome with PHOX2B gene mutation: are we missing the diagnosis?",
"type": "article-journal",
- "doi": "",
+ "doi": "10.1007/s12098-012-0837-2",
"authors": [
- ["N", "Dom\u00e9nech"],
- ["R A", "Henderson"],
- ["O J", "Finn"]
+ ["Nilay", "Nirupam"],
+ ["Rajni", "Sharma"],
+ ["Viswas", "Chhapola"],
+ ["Sandeep Kumar", "Kanwal"],
+ ["Elizabeth M", "Berry-Kravis"],
+ ["Virendra", "Kumar"]
],
- "publisher": "Journal of immunology (Baltimore, Md. : 1950)",
- "issn": "0022-1767",
- "date": "1995-11-15",
- "abstract": "Epithelial cell mucin encoded by the MUC-1 gene is overexpressed and aberrantly glycosylated on pancreatic, breast, and ovarian cancers as well as on multiple myelomas. It is recognized by patients' Ab and by T cells derived from tumor-draining lymph nodes. The T cell recognition is not MHC restricted and is specific for an epitope previously localized to the immunodominant tandem repeat region of the native mucin molecule. In search of possible MHC-restricted epitopes in the same immunodominant region, we synthesized a panel of overlapping, nine-amino acid long peptides spanning the MUC-1 tandem repeat and first examined their binding to specific human MHC class I molecules using two independent flow cytometry-based assay systems. This approach identified one peptide, p9-17 (STAPPAHGV), that bound to HLA-A1, -A2.1, -A3, and -A11. Measurements of the affinity of binding to each of these alleles, using a quantitative molecular binding assay, indicated that only the relative binding affinity to HLA-A11 was close to immunogenic values. We tested the immunogenicity of p9-17 in vitro. We detected a secondary T cell response specific for p9-17 in lymph nodes from an HLA-A11 breast cancer patient. Moreover, CTL specific for p9-17 peptide could be generated from PBL in several healthy HLA-A11 donors by primary in vitro stimulation.",
+ "publisher": "Indian journal of pediatrics",
+ "issn": "0973-7693",
+ "date": "2012-07-25",
+ "abstract": "Congenital Central Hypoventilation Syndrome is a rare disorder of autonomic and central nervous system dysfunction with impaired control of breathing. The authors report a 37- d-old girl infant with recurrent apnea requiring repeated mechanical ventilation with no evidence of neuromuscular, cardiac or lung disease. A mutation analysis of PHOX2B gene revealed 25 polyalanine repeat expansion mutation on chromosome 4p12. This article aims at raising awareness among pediatricians about molecular basis and availability of confirmatory genetic testing for diagnosis and to help with prognosis in this disorder.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7594478"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22829249"
},
{
- "id": "pmid:8579785",
+ "id": "pmid:22821709",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/8579785",
- "title": "Structure of a tumor associated antigen containing a tandemly repeated immunodominant epitope.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22821709",
+ "title": "Germline mosaicism of PHOX2B mutation accounts for familial recurrence of congenital central hypoventilation syndrome (CCHS).",
"type": "article-journal",
- "doi": "10.1080/07391102.1995.10508837",
+ "doi": "10.1002/ajmg.a.35499",
"authors": [
- ["J D", "Fontenot"],
- ["S V", "Mariappan"],
- ["P", "Catasti"],
- ["N", "Domenech"],
- ["O J", "Finn"],
- ["G", "Gupta"]
+ ["Casey M", "Rand"],
+ ["Min", "Yu"],
+ ["Lawrence J", "Jennings"],
+ ["Kelvin", "Panesar"],
+ ["Elizabeth M", "Berry-Kravis"],
+ ["Lili", "Zhou"],
+ ["Debra E", "Weese-Mayer"]
],
- "publisher": "Journal of biomolecular structure & dynamics",
- "issn": "0739-1102",
- "date": "1995-10-01",
- "abstract": "Human mucins are T or S glycosylated tandem repeat proteins. In breast cancer, mucins become under or unglycosylated. Two-dimensional nuclear magnetic resonance experiments are performed on chemically synthesized mucin tandem repeat polypeptides, (PDTRPAPGST-APPAHGVTSA)n the unglycosylated form for n=1,3 where (APDTR) constitutes the antigenic sites for the antibodies isolated form the tumors in the breast cancer patients. These studies demonstrate how the tandem repeats assemble in space giving rise to the overall tertiary structure, and the local structure and presentation of the antigenic site(APDTR) at the junction of two neighboring repeats. The NMR data reveal repeating knob-like structures connected by extended spacers. The knobs protrude away from the long-axis of Muc-1 and the predominant antigenic site (APDTR) forms the accessible tip of the knob. Multiple tandem repeats enhance the rigidity and presentation of the knob-like structures.",
+ "publisher": "American journal of medical genetics. Part A",
+ "issn": "1552-4833",
+ "date": "2012-07-20",
+ "abstract": "Congenital central hypoventilation syndrome (CCHS), a rare disorder characterized by alveolar hypoventilation and autonomic dysregulation, is caused by mutations in the PHOX2B gene. Most mutations occur de novo, but recent evidence suggests that up to 25% are inherited from asymptomatic parents with somatic mosaicism for these mutations. However, to date, germline mosaicism has not been reported. This report describes a family with recurrence of PHOX2B mutation-confirmed CCHS due to germline mosaicism. The first occurrence was a baby girl, noted on day 2 of life to have multiple episodes of apnea, bradycardia, and cyanosis while breathing room air. PHOX2B gene testing confirmed the diagnosis of CCHS with a heterozygous polyalanine repeat expansion mutation (PARM); genotype 20/27 (normal 20/20). Both parents tested negative for this mutation using fragment analysis (limit of detection<1%). Upon subsequent pregnancy [paternity confirmed using short tandem repeat (STR) analysis], amniocentesis testing identified the PHOX2B 20/27 genotype, confirmed with repeat testing. Elective abortion was performed at 21.5 weeks gestation. Testing of abortus tissue confirmed amniocentesis testing. The PHOX2B 20/27 expansion was not observed in a paternal sperm sample. This case represents the first reported family with recurrence of PHOX2B mutation-confirmed CCHS without detection of a parental carrier state or mosaicism, confirming the previously hypothesized possibility of germline mosaicism for PHOX2B mutations. This is an important finding for genetic counseling of CCHS families, suggesting that even if somatic mosaicism is not detected in parental samples, there is still reason for careful genetic counseling and consideration of prenatal testing during subsequent pregnancies.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8579785"
-},
-{
- "id": "pmid:7628867",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/7628867",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:7628867']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22821709"
},
{
- "id": "pmid:7946402",
+ "id": "pmid:22437207",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/7946402",
- "title": "Quantitation of mucin mRNA in respiratory and intestinal epithelial cells.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22437207",
+ "title": "Inheritance of polyalanine expansion mutation of PHOX2B in congenital central hypoventilation syndrome.",
"type": "article-journal",
- "doi": "10.1165/ajrcmb.11.6.7946402",
+ "doi": "10.1038/jhg.2012.27",
"authors": [
- ["J A", "Voynow"],
- ["M C", "Rose"]
+ ["Toru", "Meguro"],
+ ["Yuki", "Yoshida"],
+ ["Makiko", "Hayashi"],
+ ["Kentaro", "Toyota"],
+ ["Tesshu", "Otagiri"],
+ ["Narutaka", "Mochizuki"],
+ ["Yumiko", "Kishikawa"],
+ ["Ayako", "Sasaki"],
+ ["Kiyoshi", "Hayasaka"]
],
- "publisher": "American journal of respiratory cell and molecular biology",
- "issn": "1044-1549",
- "date": "1994-12-01",
- "abstract": "Mucin glycoproteins (mucins) are the major macromolecular constituents of mucus gels in mammalian respiratory, gastrointestinal, and reproductive tracts. Disorders of mucin glycosylation, which may result from either abnormal post-translational processing or differences in mucin protein gene expression, have been indicated in several diseases. Quantitation of mucin gene expression has been hindered by two features of human mucin genes: variable numbers of tandemly repeating nucleotides per mRNA molecule and polydisperse mRNA transcripts. We report here a method to quantitate mucin mRNA levels in epithelial cells and have evaluated three mucin genes, MUC1, MUC2, and MUC5, which are expressed in respiratory epithelium. The method uses the 3' non-tandem repeat mucin cDNA sequences, as they were shown to have a single-size transcript when amplified by the polymerase chain reaction, consistent with a one-to-one relationship with the mRNA molecule. The 3' non-tandem repeat cDNA sequences were cloned and transcribed in vitro to prepare complementary RNA (cRNA) standards. By comparison to a cRNA standard curve, mucin gene expression was evaluated in colon adenocarcinoma, pancreatic adenocarcinoma, and transformed respiratory epithelial cells and in nasal polyp tissue by slot blot analysis. CFPAC-1, a pancreatic adenocarcinoma cell line, expressed the highest MUC1 transcript levels. Colon adenocarcinoma cell lines varied in MUC2 expression levels, and one colon adenocarcinoma cell line, HT-29, had higher levels of MUC5 than MUC2. Nasal polyp tissue expressed more MUC5 mRNA than MUC1 or MUC2 mRNA. This mucin mRNA slot blot method provides a quantitative method for investigating the regulation of mucin gene expression in health and disease.",
+ "publisher": "Journal of human genetics",
+ "issn": "1435-232X",
+ "date": "2012-03-22",
+ "abstract": "Congenital central hypoventilation syndrome (CCHS; MIM 209880) is caused mostly by dominant alanine expansion (most prevalent is 7-alanine expansion) mutations in PHOX2B. More than 90% of the alanine expansion mutations had been considered to be de novo due to unequal crossover during gametogenesis. However, a recent report stated that 25% of patients inherited the alanine-expanded allele from their parents with somatic mosaicism or constitutive mutation. We studied inheritance in 45 unrelated families, and found that one patient (2%) inherited 5-alanine expansion mutation from a parent with late-onset central hypoventilation syndrome and nine patients (20%) inherited 5- to 7-alanine expansion mutation from apparently asymptomatic parents with somatic mosaicism. Analysis using a sensitive method would be recommended to all parents of CCHS proband due to high incidence of somatic mosaicism. The absence of an alanine-contracted allele (expected counterpart allele in unequal crossover) and the highest prevalence of 6-alanine expansion mutation in somatic mosaicism suggest that the somatic mosaicism is likely caused by a mechanism other than an unequal crossover, such as a replication mechanism.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7946402"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22437207"
},
{
- "id": "pmid:7514493",
+ "id": "pmid:20236122",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/7514493",
- "title": "Humoral immunity against a tandem repeat epitope of human mucin MUC-1 in sera from breast, pancreatic, and colon cancer patients.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/20236122",
+ "title": "Congenital central hypoventilation syndrome: genotype-phenotype correlation in parents of affected children carrying a PHOX2B expansion mutation.",
"type": "article-journal",
- "doi": "",
+ "doi": "10.1111/j.1399-0004.2010.01383.x",
"authors": [
- ["Y", "Kotera"],
- ["J D", "Fontenot"],
- ["G", "Pecher"],
- ["R S", "Metzgar"],
- ["O J", "Finn"]
+ ["S", "Parodi"],
+ ["C", "Vollono"],
+ ["M P", "Baglietto"],
+ ["M", "Balestri"],
+ ["M", "Di Duca"],
+ ["P A", "Landri"],
+ ["I", "Ceccherini"],
+ ["G", "Ottonello"],
+ ["M R", "Cilio"]
],
- "publisher": "Cancer research",
- "issn": "0008-5472",
- "date": "1994-06-01",
- "abstract": "Using synthetic peptides 60,80, and 105 residues long, corresponding to 3, 4, and 5.25 tandem repeats of human mucin MUC-1 protein core, as antigens in a solid-phase enzyme-linked immunosorbent assay, we screened sera from 24 breast cancer patients, 10 colon cancer patients, and 12 pancreatic cancer patients, at various stages of disease, for the presence of mucin-specific antibodies. The 105-residue peptide was superior in allowing detection of high levels of anti-mucin antibodies in 10.9% of sera in each cancer group. Another 4.3% showed intermediate reactivity. Lower levels of detection were achieved with the 80-residue peptide, and no specific reactivity was detectable with the 60-residue peptide. Anti-mucin antibodies were previously undetectable when this assay was performed with purified whole mucin or short synthetic peptides. The presence or absence of antibody did not correlate with the levels of circulating mucin or stage of disease. One highly reactive serum sample was used to identify more precisely the epitope on the long synthetic peptide to which the reactivity was directed. The reactivity of this serum specific for the 105-residue peptide was blocked by a 9-residue peptide from the NH2-terminal region of the 20-residue tandem repeat containing the previously identified immunogenic epitope APDTRP. Another 9-residue mucin peptide, from the COOH-terminal region of the tandem repeat which does not contain the APDTRP epitope, had no effect. All the mucin-specific reactivity was found to be of the IgM isotype, indicating a helper T-cell-independent response, unusual for an antibody against a peptide epitope, but not unexpected for tandemly repeated epitopes.",
+ "publisher": "Clinical genetics",
+ "issn": "1399-0004",
+ "date": "2010-02-11",
+ "abstract": "Congenital Central Hypoventilation Syndrome (CCHS) is a rare genetic disorder. Although most CCHS associated PHOX2B mutations occur de novo, about 10% of the cases are inherited from apparently asymptomatic parents, thus confirming variable expressivity and incomplete penetrance of PHOX2B mutations. Three asymptomatic parents of children affected with CCHS, and found to carry the same PHOX2B expansion mutations as their siblings, were studied by overnight polysomnography and somatic mosaicism analysis. In one case, significant sleep breathing control anomalies were detected, while the other two resulted in normal. In tissue-specific allele studies, mosaicism with a comparatively low mutant allele proportion was showed in the two unaffected adult carriers. Accurate polysomnography and assessment of the degree of somatic mosaicism should be conducted in asymptomatic carriers of PHOX2B mutations, as they may unmask subclinical but significant anomalies.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7514493"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20236122"
},
{
- "id": "pmid:21419568",
+ "id": "pmid:19608868",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21419568",
- "title": "Expansion of the phenotypic spectrum of SPG6 caused by mutation in NIPA1.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19608868",
+ "title": "MYCN promotes the expansion of Phox2B-positive neuronal progenitors to drive neuroblastoma development.",
"type": "article-journal",
- "doi": "10.1016/j.clineuro.2011.02.011",
+ "doi": "10.2353/ajpath.2009.090019",
"authors": [
- ["Juan", "Du"],
- ["Ya-Cen", "Hu"],
- ["Bei-Sha", "Tang"],
- ["Chong", "Chen"],
- ["Ying-Ying", "Luo"],
- ["Zi-Xiong", "Zhan"],
- ["Guo-Hua", "Zhao"],
- ["Hong", "Jiang"],
- ["Kun", "Xia"],
- ["Lu", "Shen"]
+ ["Goleeta", "Alam"],
+ ["Hongjuan", "Cui"],
+ ["Huilin", "Shi"],
+ ["Liqun", "Yang"],
+ ["Jane", "Ding"],
+ ["Ling", "Mao"],
+ ["William A", "Maltese"],
+ ["Han-Fei", "Ding"]
],
- "publisher": "Clinical neurology and neurosurgery",
- "issn": "1872-6968",
- "date": "2011-03-17",
- "abstract": "Hereditary spastic paraplegia type 6 (SPG6) is caused by mutations in the NIPA1 gene, this is a rare cause of HSP, until now, all the affected individuals reported displayed \"pure\" spastic paraplegia.",
+ "publisher": "The American journal of pathology",
+ "issn": "1525-2191",
+ "date": "2009-07-16",
+ "abstract": "Amplification of the oncogene MYCN is a tumorigenic event in the development of a subset of neuroblastomas that commonly consist of undifferentiated or poorly differentiated neuroblasts with unfavorable clinical outcome. The cellular origin of these neuroblasts is unknown. Additionally, the cellular functions and target cells of MYCN in neuroblastoma development remain undefined. Here we examine the cell types that drive neuroblastoma development in TH-MYCN transgenic mice, an animal model of the human disease. Neuroblastoma development in these mice begins with hyperplastic lesions in early postnatal sympathetic ganglia. We show that both hyperplasia and primary tumors are composed predominantly of highly proliferative Phox2B(+) neuronal progenitors. MYCN induces the expansion of these progenitors by both promoting their proliferation and preventing their differentiation. We further identify a minor population of undifferentiated nestin(+) cells in both hyperplastic lesions and primary tumors that may serve as precursors of Phox2B(+) neuronal progenitors. These findings establish the identity of neuroblasts that characterize the tumor phenotype and suggest a cellular pathway by which MYCN can promote neuroblastoma development.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21419568"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19608868"
},
{
- "id": "pmid:9736780",
+ "id": "pmid:17909190",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/9736780",
- "title": "CAG repeat expansion in autosomal dominant familial spastic paraparesis: novel expansion in a subset of patients.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17909190",
+ "title": "Central hypoventilation with PHOX2B expansion mutation presenting in adulthood.",
"type": "article-journal",
- "doi": "10.1093/hmg/7.11.1779",
+ "doi": "10.1136/thx.2006.068908",
"authors": [
- ["K F", "Benson"],
- ["M", "Horwitz"],
- ["J", "Wolff"],
- ["K", "Friend"],
- ["E", "Thompson"],
- ["S", "White"],
- ["R I", "Richards"],
- ["W H", "Raskind"],
- ["T D", "Bird"]
+ ["S", "Barratt"],
+ ["A H", "Kendrick"],
+ ["F", "Buchanan"],
+ ["A T", "Whittle"]
],
- "publisher": "Human molecular genetics",
- "issn": "0964-6906",
- "date": "1998-10-01",
- "abstract": "Autosomal dominant familial spastic paraplegia (FSP) is a genetically heterogeneous neurodegenerative disorder displaying anticipation for which three loci have been mapped to the chromosomal positions 14q11.2-q24.3 (SPG3), 2p21-p24 (SPG4) and 15q11.1 (SPG6). The repeat expansion detection (RED) method has been used to demonstrate expanded CAG repeats in some FSP families that map to SPG4. We analyzed 20 FSP families, including four for which there is evidence for linkage to SPG4, and found that in most cases the repeat expansion detected by RED is due to non-pathogenic expansions of the chromosome 18q21.1 SEF2-1 or 17q21.3 ERDA1 locus. Polymorphic expansions at SEF2-1 and ERDA1 appear frequent and may confound RED studies in the search for genes causing disorders demonstrating anticipation. In six FSP families, however, CAG repeat expansion was detected in a subset of affected and at-risk individuals that did not result from expansion of the SEF2-1 and ERDA1 loci. Overall, 11 of 37 (30%) of the FSP patients with a CAG/CTG repeat expansion are unaccounted for by the SEF2-1 and ERDA1 loci, compared with two of 23 (9%) of the unaffected at-risk individuals and none of 19 controls. In the majority of cases these novel expansions were shorter than those previously reported.",
+ "publisher": "Thorax",
+ "issn": "0040-6376",
+ "date": "2007-10-01",
+ "abstract": "Congenital central hypoventilation syndrome most commonly presents in neonates with sleep related hypoventilation; late onset cases have occurred up to the age of 10 years. It is associated with mutations in the PHOX2B gene, encoding a transcription factor involved in autonomic nervous system development. The case history is described of an adult who presented with chronic respiratory failure due to PHOX2B mutation-associated central hypoventilation and an impaired response to hypercapnia.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9736780"
-},
-{
- "id": "pmid:25101480",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/25101480",
- "note": "WARNING: Couldn't parse Manubot response: list index out of range"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17909190"
},
{
- "id": "pmid:40015643",
+ "id": "pmid:17045833",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/40015643",
- "title": "Dissecting the mechanism of NOP56 GGCCUG repeat-associated non-AUG translation using cell-free translation systems.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17045833",
+ "title": "Geldanamycin promotes nuclear localisation and clearance of PHOX2B misfolded proteins containing polyalanine expansions.",
"type": "article-journal",
- "doi": "10.1016/j.jbc.2025.108360",
+ "doi": "10.1016/j.biocel.2006.08.014",
"authors": [
- ["Mayuka", "Hasumi"],
- ["Hayato", "Ito"],
- ["Kodai", "Machida"],
- ["Tatsuya", "Niwa"],
- ["Tomoya", "Taminato"],
- ["Yoshitaka", "Nagai"],
- ["Hiroaki", "Imataka"],
- ["Hideki", "Taguchi"]
+ ["Tiziana", "Bachetti"],
+ ["Paola", "Bocca"],
+ ["Silvia", "Borghini"],
+ ["Ivana", "Matera"],
+ ["Ignazia", "Prigione"],
+ ["Roberto", "Ravazzolo"],
+ ["Isabella", "Ceccherini"]
],
- "publisher": "The Journal of biological chemistry",
- "issn": "1083-351X",
- "date": "2025-02-25",
- "abstract": "The repeat expansion in the human genome contributes to neurodegenerative disorders such as spinocerebellar ataxia (SCA) and amyotrophic lateral sclerosis. Transcripts with repeat expansions undergo noncanonical translation called repeat-associated non-AUG (RAN) translation. The NOP56 gene, implicated in SCA36, contains a GGCCTG repeat in its first intron. In tissues of patients with SCA36, poly (Gly-Pro) and poly (Pro-Arg) peptides, likely produced through NOP56 RAN translation in (NOP56-RAN), have been detected. However, the detailed mechanism underlying NOP56-RAN remains unclear. To address this, we used cell-free translation systems to investigate the mechanism of NOP56-RAN and identified the following features. (i) Translation occurs in all reading frames of the sense strand of NOP56 intron 1. (ii) Translation is initiated in a 5' cap-dependent manner from near-cognate start codons upstream of the GGCCUG repeat in each frame. (iii) Longer GGCCUG repeats enhance NOP56-RAN. (iv) A frameshift occurs within the GGCCUG repeat. These findings provide insights into the similarities between NOP56-RAN and other types of RAN translation.",
+ "publisher": "The international journal of biochemistry & cell biology",
+ "issn": "1357-2725",
+ "date": "2006-09-14",
+ "abstract": "Polyalanine expansions in the PHOX2B gene have been detected in the vast majority of patients affected with congenital central hypoventilation syndrome, a neurocristopathy characterized by absence of adequate control of breathing, especially during sleep, with decreased sensitivity to hypoxia and hypercapnia. The correlation between length of the alanine expanded tracts and severity of congenital central hypoventilation syndrome respiratory phenotype has been confirmed by length-dependent cytoplasmic PHOX2B retention with formation of aggregates. To deepen into the molecular mechanisms mediating the effects of PHOX2B polyalanine expansions, we have set up experiments aimed at assessing the fate of cells characterized by PHOX2B polyalanine aggregates. In particular, we have observed that activation of the heat shock response by the drug geldanamycin is efficient both in preventing formation and in inducing clearance of PHOX2B pre-formed polyalanine aggregates in COS-7 cells expressing PHOX2B-GFP fused proteins, and ultimately also in rescuing the PHOX2B ability to transactivate the Dopamine-beta-Hydroxilase promoter. In addition, we have demonstrated elimination of PHOX2B mutant proteins by the proteasome and autophagy, two cellular mechanisms already been involved in the clearance of proteins containing expanded polyglutamine and polyalanine tracts. Moreover, our data suggest that geldanamycin effects on PHOX2B aggregates may be also mediated by the proteasome pathway. Finally, analysis of cellular toxicity due to polyalanine aggregates has confirmed the occurrence of cell apoptosis consequent to expression of PHOX2B carrying the longest expanded alanine tract and shown that geldanamycin can delay cell progression toward the most advanced apoptotic stages.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40015643"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17045833"
},
{
- "id": "pmid:36572080",
+ "id": "pmid:16888290",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/36572080",
- "title": "RNA G-quadruplex in live cells lighted-up by a thiazole orange analogue for SCA36 identification.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/16888290",
+ "title": "Congenital central hypoventilation syndrome: PHOX2B mutations and phenotype.",
"type": "article-journal",
- "doi": "10.1016/j.ijbiomac.2022.12.231",
+ "doi": "10.1164/rccm.200602-305oc",
"authors": [
- ["Ranran", "Sun"],
- ["Xiaomeng", "Guo"],
- ["Dawei", "Yang"],
- ["Xinchen", "Cai"],
- ["Qian", "Li"],
- ["Li", "Yao"],
- ["Hongxia", "Sun"],
- ["Yalin", "Tang"]
+ ["Elizabeth M", "Berry-Kravis"],
+ ["Lili", "Zhou"],
+ ["Casey M", "Rand"],
+ ["Debra E", "Weese-Mayer"]
],
- "publisher": "International journal of biological macromolecules",
- "issn": "1879-0003",
- "date": "2022-12-23",
- "abstract": "SCA36 is a neurodegenerative disease mainly caused by the abnormal expansion of the GGGCCT repeat sequence in intron 1 of NOP56. The RNA sequences of this gene are expected to form large amounts of G-quadruplexes in the cytoplasm, which may be a potential intervention and detection target for SCA36. Here, we have developed a small-molecular compound named TCB-1, which shows good selectivity to the G-quadruplex structure, and its fluorescence can be enhanced by hundreds of folds. Interestingly, TCB-1 can avoid lysosome capture, evenly disperse in the cytoplasm, and selectively light up the cytoplasmic RNA G-quadruplexes. This property allows TCB-1 to sensitively detect the increased formation of cytoplasmic RNA G-quadruplexes in SCA36 model cells. This work not only provides new ideas for the design of small-molecule compounds targeting RNA G-quadruplexes in living cells, but also intuitively demonstrates the increased formation of RNA G-quadruplexes caused by NOP56 gene mutation, providing a possible tool for the detection of SCA36.",
+ "publisher": "American journal of respiratory and critical care medicine",
+ "issn": "1073-449X",
+ "date": "2006-08-03",
+ "abstract": "Congenital central hypoventilation syndrome (CCHS), a unique disorder of respiratory control associated with Hirschsprung disease (HSCR) and tumors of neural crest origin, results from polyalanine repeat expansion mutations in the paired-like homeobox (PHOX)2B gene in more than 90% of cases, and alternative PHOX2B mutations in remaining cases.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36572080"
-},
-{
- "id": "pmid:32407596",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/32407596",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:32407596']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16888290"
},
{
- "id": "pmid:32270466",
+ "id": "pmid:40488265",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/32270466",
- "title": "Cerebellar Cognitive Affective Syndrome in Costa da Morte Ataxia (SCA36).",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/40488265",
+ "title": "Current understanding of skeletal muscle repeat expansion disorders.",
"type": "article-journal",
- "doi": "10.1007/s12311-020-01110-0",
+ "doi": "10.1097/wco.0000000000001394",
"authors": [
- ["R", "Mart\u00ednez-Regueiro"],
- ["M", "Arias"],
- ["R", "Cruz"],
- ["B", "Quint\u00e1ns"],
- ["T", "Labella-Caballero"],
- ["M", "Pardo"],
- ["J", "Pardo"],
- ["M", "Garc\u00eda-Murias"],
- ["A", "Carracedo"],
- ["M-J", "Sobrido"],
- ["M", "Fern\u00e1ndez-Prieto"]
- ],
- "publisher": "Cerebellum (London, England)",
- "issn": "1473-4230",
- "date": "2020-08-01",
- "abstract": "SCA36 is an autosomal dominant spinocerebellar ataxia (SCA) affecting many families from Costa da Morte, a northwestern region of Spain. It is caused by an intronic GGCCTG repeat expansion in NOP56. In order to characterize the cognitive and affective manifestations of this cerebellar disease, a group of 30 SCA36 mutation carriers (11 preataxic and 19 ataxic patients) were assessed with a comprehensive battery of standardized tests. Phonological verbal fluency - but not semantic fluency - was already mildly impaired in preataxic subjects. In ataxic patients, both phonological and semantic fluencies were significantly below normal. Depression, while more frequent and prominent in ataxic patients, was also often present in the preataxic stage. This is the first systematic study supporting the presence of a mild cerebellar cognitive and affective syndrome in SCA36. Routine evaluation of cognitive and emotional spheres in SCA36 patients as well as asymptomatic mutation carriers should allow early detection and timely therapeutic intervention.",
+ ["Manon", "Boivin"],
+ ["Gianina", "Ravenscroft"]
+ ],
+ "publisher": "Current opinion in neurology",
+ "issn": "1473-6551",
+ "date": "2025-06-10",
+ "abstract": "Here, we summarize the current knowledge about the genetics and proposed mechanisms of disease underlying skeletal muscle short tandem repeat (STR) expansion disorders.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32270466"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40488265"
},
{
- "id": "pmid:26661328",
+ "id": "pmid:29029963",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26661328",
- "title": "Genetic and clinical analysis of spinocerebellar ataxia type 36 in Mainland China.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/29029963",
+ "title": "Genetic risk factors in Finnish patients with Parkinson's disease.",
"type": "article-journal",
- "doi": "10.1111/cge.12706",
+ "doi": "10.1016/j.parkreldis.2017.09.021",
"authors": [
- ["S", "Zeng"],
- ["J", "Zeng"],
- ["M", "He"],
- ["X", "Zeng"],
- ["Y", "Zhou"],
- ["Z", "Liu"],
- ["K", "Xia"],
- ["Q", "Pan"],
- ["H", "Jiang"],
- ["L", "Shen"],
- ["X", "Yan"],
- ["B", "Tang"],
- ["J", "Wang"]
+ ["Susanna", "Yl\u00f6nen"],
+ ["Ari", "Siitonen"],
+ ["Michael A", "Nalls"],
+ ["Pauli", "Ylikotila"],
+ ["Jaana", "Autere"],
+ ["Johanna", "Eerola-Rautio"],
+ ["Raphael", "Gibbs"],
+ ["Mikko", "Hiltunen"],
+ ["Pentti J", "Tienari"],
+ ["Hilkka", "Soininen"],
+ ["Andrew B", "Singleton"],
+ ["Kari", "Majamaa"]
],
- "publisher": "Clinical genetics",
- "issn": "1399-0004",
- "date": "2016-01-20",
- "abstract": "Spinocerebellar ataxia type 36 (SCA36) is a new SCA subtype recently reported in Japanese and Spanish pedigrees. To assess the frequency and clinical characteristics of SCA36 in patients from Mainland China, we combined the repeat-primed polymerase chain reaction method and Southern blot analysis to detect the GGCCTG hexanucleotide repeats of NOP56 in 364 probands with SCA, 126 probands with hereditary spastic paraplegia and 99 probands with amyotrophic lateral sclerosis (ALS). Systematic and targeted clinical evaluations and investigations were conducted in the SCA36 patients. As a result, eight autosomal dominant spinocerebellar ataxia (ADCA) pedigrees (a total of 13 patients) and one sporadic SCA (S-SCA) patient were identified as SCA36 in the SCA cohort, accounting for approximately 1.60% of the cases in the ADCA group and 0.32% of those in the S-SCA group in Mainland China. The characteristics include late onset and slow progression accompanied by acoustic impairments and 'possible' ALS phenotype in patients from Mainland China.",
+ "publisher": "Parkinsonism & related disorders",
+ "issn": "1873-5126",
+ "date": "2017-09-29",
+ "abstract": "Variation contributing to the risk of Parkinson's disease (PD) has been identified in several genes and at several loci including GBA, SMPD1, LRRK2, POLG1, CHCHD10 and MAPT, but the frequencies of risk variants seem to vary according to ethnic background. Our aim was to analyze how variation in these genes contributes to PD in the Finnish population.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26661328"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29029963"
},
{
- "id": "pmid:24985895",
+ "id": "pmid:25767537",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/24985895",
- "title": "Characteristic RNA foci of the abnormal hexanucleotide GGCCUG repeat expansion in spinocerebellar ataxia type 36 (Asidan).",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25767537",
+ "title": "The POLG Polyglutamine Tract Variants in Iranian Patients with Multiple Sclerosis.",
"type": "article-journal",
- "doi": "10.1111/ene.12491",
+ "doi": "",
"authors": [
- ["W", "Liu"],
- ["Y", "Ikeda"],
- ["N", "Hishikawa"],
- ["T", "Yamashita"],
- ["K", "Deguchi"],
- ["K", "Abe"]
+ ["Mehri", "Khatami"],
+ ["Mohammad Mehdi", "Heidari"],
+ ["Reza", "Mansouri"],
+ ["Fatemeh", "Mousavi"]
],
- "publisher": "European journal of neurology",
- "issn": "1468-1331",
- "date": "2014-07-02",
- "abstract": "Spinocerebellar ataxia type 36 (SCA36), also called Asidan, is an autosomal-dominant neurodegenerative disorder identified as a hexanucleotide GGCCTG repeat expansion in the first intron 1 of the NOP56 gene. In the present study, for the first time an autopsy sample from an Asidan patient was examined and cytoplasmic inclusions and (GGCCUG)n repeat RNA foci were detected.",
+ "publisher": "Iranian journal of child neurology",
+ "issn": "1735-4668",
+ "date": "2015-01-01",
+ "abstract": "Multiple Sclerosis (MS) is a common disease of the central nervous system. The interaction between inflammatory and neurodegenerative processes typically results in irregular neurological disturbances followed by progressive disability. Mitochondrial dysfunction has been implicated in neurodegenerative disorders. The DNA polymerase-gamma (POLG) gene, which encodes the catalytic subunit of enzyme responsible for directing mtDNA replication, contains a poly glutamine tract (poly-Q) in the N-terminal, encoded by a CAG sequence in exon 2.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24985895"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25767537"
},
{
- "id": "pmid:22744658",
+ "id": "pmid:20803511",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/22744658",
- "title": "Clinical features of SCA36: a novel spinocerebellar ataxia with motor neuron involvement (Asidan).",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/20803511",
+ "title": "POLG, but not PEO1, is a frequent cause of cerebellar ataxia in Central Europe.",
"type": "article-journal",
- "doi": "10.1212/wnl.0b013e318260436f",
+ "doi": "10.1002/mds.23286",
"authors": [
- ["Yoshio", "Ikeda"],
- ["Yasuyuki", "Ohta"],
- ["Hatasu", "Kobayashi"],
- ["Miyuki", "Okamoto"],
- ["Kazuhiro", "Takamatsu"],
- ["Taisei", "Ota"],
- ["Yasuhiro", "Manabe"],
- ["Koichi", "Okamoto"],
- ["Akio", "Koizumi"],
- ["Koji", "Abe"]
+ ["Julia", "Schicks"],
+ ["Matthis", "Synofzik"],
+ ["Claudia", "Schulte"],
+ ["Ludger", "Sch\u00f6ls"]
],
- "publisher": "Neurology",
- "issn": "1526-632X",
- "date": "2012-06-27",
- "abstract": "To characterize the phenotype of spinocerebellar ataxia type 36 (SCA36), a novel dominant disorder (nicknamed \"Asidan\") caused by a hexanucleotide GGCCTG repeat expansion in intron 1 of the NOP56 gene.",
+ "publisher": "Movement disorders : official journal of the Movement Disorder Society",
+ "issn": "1531-8257",
+ "date": "2010-11-15",
+ "abstract": "Nuclear genes, in particular mitochondrial polymerase gamma (POLG) and PEO1, have been increasingly recognized to cause mitochondrial diseases. Both genes assume a complementary role as part of the mitochondrial DNA (mtDNA) replication fork and, accordingly, seem to present with largely overlapping phenotypical spectra. We assessed the frequency and phenotypic spectrum of PEO1 compared to POLG mutations in a cohort of 80 patients with cerebellar ataxia for which common repeat expansion diseases had been excluded. Patients were selected to present additional features previously described for PEO1 mutations, namely early age of onset, progressive external ophthalmoplegia (PEO), or epilepsy. Whereas PEO1 mutations were not found in our cohort, POLG frequently caused ataxia with PEO (47%), psychiatric comorbidities (20%) and, more rarely, with epilepsy (14%). Thus, PEO1 is rare in Central Europe even in those patients displaying characteristic phenotypic features. In contrast, POLG is rather common in Central European ataxia patients. It should be particularly considered in ataxia patients with PEO, psychiatric comorbidities, and/or sensory neuropathy, even if characteristic mitochondrial extra-CNS features are absent.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22744658"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20803511"
},
{
- "id": "pmid:40635536",
+ "id": "pmid:12036482",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/40635536",
- "title": "Diverse Clinical Phenotypes of Neuronal Intranuclear Inclusion Disease in South Korea.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/12036482",
+ "title": "Lack of correlation between length variation in the DNA polymerase gamma gene CAG repeat and lactic acidosis or neuropathy during antiretroviral treatment.",
"type": "article-journal",
- "doi": "10.3988/jcn.2024.0526",
+ "doi": "10.1089/088922202753747879",
"authors": [
- ["Min Young", "Chun"],
- ["Sang Won", "Seo"],
- ["Hyemin", "Jang"],
- ["Duk L", "Na"],
- ["Seongmi", "Kim"],
- ["Na Kyung", "Lee"],
- ["Seung-Yeon", "Lee"],
- ["Kyung Bok", "Lee"],
- ["Jinyoung", "Youn"],
- ["Ja-Hyun", "Jang"],
- ["Na-Yeon", "Jung"],
- ["Eun Hye", "Lee"],
- ["Jee Hyang", "Jeong"],
- ["Soo Jin", "Yoon"],
- ["Hyung Chan", "Kim"],
- ["Joonwon", "Lee"],
- ["Seongho", "Park"],
- ["Jinse", "Park"],
- ["Heejeong", "Jeong"],
- ["Tae-Won", "Yang"],
- ["Eungseok", "Oh"],
- ["Eun-Joo", "Kim"],
- ["Jiyoung", "Kim"],
- ["Ji Eun", "Lee"],
- ["Ji-Yun", "Park"],
- ["Takeshi", "Mizuguchi"],
- ["Shinichi", "Kameyama"],
- ["Naomichi", "Matsumoto"],
- ["Yeon-Lim", "Suh"],
- ["Hee Jin", "Kim"]
+ ["Xianghong", "Chen"],
+ ["Jaap", "Goudsmit"],
+ ["Antoinette C", "van der Kuyl"]
],
- "publisher": "Journal of clinical neurology (Seoul, Korea)",
- "issn": "1738-6586",
- "date": "2025-07-01",
- "abstract": "Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disease characterized by a wide range of clinical manifestations. GGC-repeat expansion in",
+ "publisher": "AIDS research and human retroviruses",
+ "issn": "0889-2229",
+ "date": "2002-05-20",
+ "abstract": "Antiretroviral therapy, although successful in reducing HIV load and accordingly decreasing the incidence of HIV infection-related symptoms, has its drawbacks in the form of severe side effects. Recognized drug-related side effects are, for example, nausea, fatigue, lactic acidosis, neuropathy, lipodystrophy, and myopathy. Because not all patients experience these side effects, genetic factors could be involved. It is believed that the main toxicity of nucleoside analog drugs is due to a decrease in mitochondrial function, possibly by inhibition of mitochondrial DNA (mtDNA) replication. mtDNA is replicated by a multienzyme complex, the main component of which is the nuclear-encoded DNA polymerase gamma. Presently, the only known variation in the DNA polymerase gamma gene is variation in the number of CAG repeats in the second exon. To investigate whether CAG repeat expansion or mutations in the DNA polymerase gamma (POLG) gene could predispose to peripheral neuropathy or lactic acidosis, we have sequenced part of the second exon of the DNA polymerase gamma gene, containing the CAG repeat, of 59 drug-treated HIV-infected patients, 11 of whom experienced drug-induced neuropathy, and 3 of whom died from lactic acidosis. No correlation was found between numbers of CAG repeats and any of the symptoms. The coding regions of the POLG gene from the three lactic acidosis patients were then completely sequenced, but no mutations were found. In addition, no variation was detected in exons 3, 8, and 19 of seven neuropathy patients and three control subjects without symptoms. These exons were the only sites of amino acid changes between human and chimpanzee POLG genes, and were chosen as targets of tolerated variation.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40635536"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12036482"
},
{
- "id": "pmid:40517194",
+ "id": "pmid:38798069",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/40517194",
- "title": "Retinal degeneration as an initial manifestation in a patient with neuronal intranuclear inclusion disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38798069",
+ "title": "Role of B\u03b21 overexpression in the pathogenesis of SCA12.",
"type": "article-journal",
- "doi": "10.1007/s10633-025-10035-0",
+ "doi": "10.1002/mds.29839",
"authors": [
- ["Shijing", "Wu"],
- ["Ailing", "Sui"],
- ["Qianyi", "Zhan"],
- ["Qiuli", "Fu"],
- ["Li", "Zhang"]
+ ["Chengqian", "Zhou"],
+ ["Fan", "Tang"],
+ ["Tao", "Dong"],
+ ["Hans B", "Liu"],
+ ["Leon", "Deng"],
+ ["Russell L", "Margolis"],
+ ["Pan P", "Li"]
],
- "publisher": "Documenta ophthalmologica. Advances in ophthalmology",
- "issn": "1573-2622",
- "date": "2025-06-14",
- "abstract": "Neuronal intranuclear inclusion disease (NIID) is a rare autosomal dominant, progressive neurodegenerative disorder characterized by a broad spectrum of clinical conditions, including pyramidal and extrapyramidal symptoms, cerebellar ataxia, cognitive decline and dementia, peripheral neuropathy, and autonomic dysfunction.",
+ "publisher": "Movement disorders : official journal of the Movement Disorder Society",
+ "issn": "1531-8257",
+ "date": "2024-05-26",
+ "abstract": "Spinocerebellar ataxia type 12 (SCA12) is a neurodegenerative disease caused by a CAG/CTG repeat expansion at the PPP2R2B locus.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40517194"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38798069"
},
{
- "id": "pmid:40515658",
+ "id": "pmid:38711441",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/40515658",
- "title": "Psychiatric-onset neuronal intranuclear inclusion disease in a psychiatry-based dementia-enriched cohort in Japan.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38711441",
+ "title": "Molecular clues unveiling spinocerebellar ataxia type-12 pathogenesis.",
"type": "article-journal",
- "doi": "10.1111/pcn.13854",
+ "doi": "10.1016/j.isci.2024.109768",
"authors": [
- ["Tesshin", "Miyamoto"],
- ["Kohji", "Mori"],
- ["Shoshin", "Akamine"],
- ["Shizuko", "Kondo"],
- ["Shiho", "Gotoh"],
- ["Ryota", "Uozumi"],
- ["Sumiyo", "Umeda"],
- ["Hanako", "Koguchi-Yoshioka"],
- ["Satoshi", "Nojima"],
- ["Daiki", "Taomoto"],
- ["Yuto", "Satake"],
- ["Takashi", "Suehiro"],
- ["Hideki", "Kanemoto"],
- ["Kenji", "Yoshiyama"],
- ["Takashi", "Morihara"],
- ["Manabu", "Ikeda"]
+ ["Manish", "Kumar"],
+ ["Shweta", "Sahni"],
+ ["Vivekanand", "A"],
+ ["Deepak", "Kumar"],
+ ["Neetu", "Kushwah"],
+ ["Divya", "Goel"],
+ ["Himanshi", "Kapoor"],
+ ["Achal K", "Srivastava"],
+ ["Mohammed", "Faruq"]
],
- "publisher": "Psychiatry and clinical neurosciences",
- "issn": "1440-1819",
- "date": "2025-06-14",
- "abstract": "A GGC repeat expansion in the 5' untranslated region of NOTCH2NLC is a genetic cause of Neuronal Intranuclear Inclusion Disease (NIID) that exhibits cognitive, motor, and autonomic dysfunction. Our objective is to determine whether there are undiagnosed NIID cases in a psychiatry-based dementia-enriched cohort and to identify their clinical characteristics.",
+ "publisher": "iScience",
+ "issn": "2589-0042",
+ "date": "2024-04-18",
+ "abstract": "Spinocerebellar Ataxia type-12 (SCA12) is a neurodegenerative disease caused by tandem CAG repeat expansion in the 5'-UTR/non-coding region of",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40515658"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38711441"
},
{
- "id": "pmid:39920690",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/39920690",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:39920690']' timed out after 3 seconds"
+ "id": "pmid:30130680",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30130680",
+ "title": "Generation of three spinocerebellar ataxia type-12 patients derived induced pluripotent stem cell lines (IGIBi002-A, IGIBi003-A and IGIBi004-A).",
+ "type": "article-journal",
+ "doi": "10.1016/j.scr.2018.08.008",
+ "authors": [
+ ["Deepak", "Kumar"],
+ ["Ashaq", "Hussain"],
+ ["Achal K", "Srivastava"],
+ ["Mitali", "Mukerji"],
+ ["Odity", "Mukherjee"],
+ ["Mohammed", "Faruq"]
+ ],
+ "publisher": "Stem cell research",
+ "issn": "1876-7753",
+ "date": "2018-08-14",
+ "abstract": "Spinocerebellar ataxia type-12 (SCA12) is a neurological disorder caused due to triplet (CAG) repeat expansion in 5' UTR of PPP2R2B. It is one of the most prominent SCA-subtype in Indian population and till date no patient specific models have been described. Human-induced-pluripotent-stem cell (HiPSC) based disease modelling has become the next generation tool for studying various human pathologies. In the present study we established three SCA12 patient specific iPSC lines. All the generated lines have shown pluripotency markers, normal karyotype, in-vitro three germ layers differentiation potential, vector clearance, SCA12 mutation, parental genomic identity and contamination free culture.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30130680"
},
{
- "id": "pmid:39529621",
+ "id": "pmid:25586539",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/39529621",
- "title": "Neuronal Intranuclear Inclusion Disease Presenting with Acute-Onset Dementia and Cortical Edema: A Case Report.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25586539",
+ "title": "Unusual cerebral white matter change in a Chinese family with Spinocerebellar ataxia type 12.",
"type": "article-journal",
- "doi": "10.3389/fneur.2024.1464991",
+ "doi": "10.1016/j.jns.2014.12.045",
"authors": [
- ["Xiao", "Feng"],
- ["Yue", "Li"],
- ["Qin", "Zhao"],
- ["Shabei", "Xu"]
+ ["Tao", "Hu"],
+ ["Bi", "Zhao"],
+ ["Qian-qian", "Wei"],
+ ["Huifang", "Shang"]
],
- "publisher": "Frontiers in neurology",
- "issn": "1664-2295",
- "date": "2024-10-28",
- "abstract": "Neuronal Intranuclear Inclusion Disease (NIID) is a neurodegenerative disorder characterized by the formation of eosinophilic inclusions in the neurons, visceral and skin cells. The cause is associated with the GGC nucleotide repeat expansion in the NOTCH2NLC gene. The imaging hallmark of NIID is hyperintensities on diffusion-weighted imaging (DWI) at the corticomedullary junction. Clinical manifestations of NIID are highly heterogeneous. Here, we report a case of NIID presenting with acute-onset dementia and cortical edema.",
+ "publisher": "Journal of the neurological sciences",
+ "issn": "1878-5883",
+ "date": "2015-01-05",
+ "abstract": "In a Chinese family with Spinocerebellar ataxia type 12 (SCA12), presenting with action tremor, mild cerebellar dysfunction, and hyperreflexia, genetic testing revealed abnormal CAG repeat length in the brain-specific protein phosphatase 2, regulatory subunit B, beta isoform (PPP2R2B) gene. To our knowledge, this is the first report on patients with SCA12 presenting with prominent cerebral white matter change besides cerebral and/or cerebellar atrophy.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39529621"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25586539"
},
{
- "id": "pmid:39505310",
+ "id": "pmid:25274186",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/39505310",
- "title": "CGG Repeat Expansion in",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25274186",
+ "title": "Diffusion tensor imaging of spinocerebellar ataxia type 12.",
"type": "article-journal",
- "doi": "10.3988/jcn.2023.0486",
+ "doi": "10.12659/msm.891104",
"authors": [
- ["Jing", "Ma"],
- ["Huiqiu", "Zhang"],
- ["Bing", "Meng"],
- ["Jiangbo", "Qin"],
- ["Hongye", "Liu"],
- ["Xiaomin", "Pang"],
- ["Rongjuan", "Zhao"],
- ["Juan", "Wang"],
- ["Xueli", "Chang"],
- ["Junhong", "Guo"],
- ["Wei", "Zhang"]
+ ["Haitao", "Li"],
+ ["Jingjing", "Ma"],
+ ["Xiaoning", "Zhang"]
],
- "publisher": "Journal of clinical neurology (Seoul, Korea)",
- "issn": "1738-6586",
- "date": "2024-11-01",
- "abstract": "CGG repeat expansion in the 5' untranslated region (5'UTR) of the Notch 2 N-terminal-like C gene (",
+ "publisher": "Medical science monitor : international medical journal of experimental and clinical research",
+ "issn": "1643-3750",
+ "date": "2014-10-02",
+ "abstract": "Spinocerebellar ataxias (SCAs) are autosomal-dominant neurodegenerative diseases that are clinically and genetically heterogeneous. SCAs are characterized by a range of neurological symptoms. SCA12 is an autosomal-dominant (AD) ataxia caused by a CAG repeat expansion mutation in a presumed promoter region of the gene PPP2R2B in a non-coding region on chromosome 5q32. This study sought to determine changes in different positions in a single Uyghur SCA12 pedigree by measuring the apparent diffusion coefficient (ADC) and fractional anisotropy (FA).",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39505310"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25274186"
},
{
- "id": "pmid:38779172",
+ "id": "pmid:18484086",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/38779172",
- "title": "Prevalence and Characterization of",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18484086",
+ "title": "PPP2R2B CAG repeat length in the Han Chinese in Taiwan: Association analyses in neurological and psychiatric disorders and potential functional implications.",
"type": "article-journal",
- "doi": "10.1212/nxg.0000000000200147",
+ "doi": "10.1002/ajmg.b.30785",
"authors": [
- ["Seungbok", "Lee"],
- ["Jihoon G", "Yoon"],
- ["Juhyeon", "Hong"],
- ["Taekeun", "Kim"],
- ["Narae", "Kim"],
- ["Jana", "Vandrovcova"],
- ["Wai Yan", "Yau"],
- ["Jaeso", "Cho"],
- ["Sheehyun", "Kim"],
- ["Man Jin", "Kim"],
- ["Soo Yeon", "Kim"],
- ["Soon-Tae", "Lee"],
- ["Kon", "Chu"],
- ["Sang Kun", "Lee"],
- ["Han-Joon", "Kim"],
- ["Jungmin", "Choi"],
- ["Jangsup", "Moon"],
- ["Jong-Hee", "Chae"]
+ ["Chiung-Mei", "Chen"],
+ ["Yi-Ting", "Hou"],
+ ["Ju-Yun", "Liu"],
+ ["Yih-Ru", "Wu"],
+ ["Chih-Hsin", "Lin"],
+ ["Hon-Chung", "Fung"],
+ ["Wen-Chuin", "Hsu"],
+ ["Yuying", "Hsu"],
+ ["Shen-Hung", "Lee"],
+ ["Hsiu-Mei", "Hsieh-Li"],
+ ["Ming-Tsan", "Su"],
+ ["Shui-Tein", "Chen"],
+ ["Hsien-Yuan", "Lane"],
+ ["Guey-Jen", "Lee-Chen"]
],
- "publisher": "Neurology. Genetics",
- "issn": "2376-7839",
- "date": "2024-05-20",
- "abstract": "GGC repeat expansions in the",
+ "publisher": "American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics",
+ "issn": "1552-485X",
+ "date": "2009-01-05",
+ "abstract": "PPP2R2B, a protein widely expressed in neurons throughout the brain, regulates the protein phosphatase 2A (PP2A) activity for the microtubule-associated protein tau and other substrates. Altered PP2A activity has been implicated in spinocerebellar ataxia 12, Alzheimer's disease (AD), and other tauopathies. Through a case-control study and a reporter assay, we investigated the association of PPP2R2B CAG repeat polymorphism with Taiwanese AD, essential tremor (ET), Parkinson's disease (PD), and schizophrenia and clarified the functional implication of this polymorphism. The distribution of the alleles was not significantly different between patients and controls, with 68.6-76.1% alleles at lengths of 10, 13, and 16 triplets. No expanded alleles were detected in either group. However, the frequency of the individuals carrying the short 5-, 6-, and 7-triplet alleles was notably higher in patients with AD (5/180 [2.8%], Fisher's exact test, P = 0.003; including 2 homozygotes) and ET (4/132 [3.0%], Fisher's exact test, P < 0.001) than in the controls (1/625 [0.2%]). The PPP2R2B transcriptional activity was significantly lower in the luciferase reporter constructs containing the (CAG)(5-7) allele than in those containing the common 10-, 13-, and 16-triplet alleles in both neuroblastoma and embryonic kidney cells. Therefore, our preliminary results suggest that the PPP2R2B gene CAG repeat polymorphism may be functional and may, in part, play a role in conferring susceptibility to AD and ET in Taiwan.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38779172"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18484086"
},
{
- "id": "pmid:38579412",
+ "id": "pmid:11171892",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/38579412",
- "title": "Neuronal intranuclear inclusion disease in New Zealand: A novel discovery.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11171892",
+ "title": "SCA-12: Tremor with cerebellar and cortical atrophy is associated with a CAG repeat expansion.",
"type": "article-journal",
- "doi": "10.1016/j.jns.2024.122987",
+ "doi": "10.1212/wnl.56.3.299",
"authors": [
- ["Tony", "Zhang"],
- ["Andrew", "Chancellor"],
- ["Bernard", "Liem"],
- ["Clinton", "Turner"],
- ["David", "Hutchinson"],
- ["Edward", "Wong"],
- ["Emma", "Glamuzina"],
- ["Jae Beom", "Hong"],
- ["James", "Cleland"],
- ["Nicholas", "Child"],
- ["Richard H", "Roxburgh"],
- ["Shilpan", "Patel"],
- ["Yi-Chung", "Lee"],
- ["Yi-Chu", "Liao"],
- ["Neil E", "Anderson"]
+ ["E", "O'Hearn"],
+ ["S E", "Holmes"],
+ ["P C", "Calvert"],
+ ["C A", "Ross"],
+ ["R L", "Margolis"]
],
- "publisher": "Journal of the neurological sciences",
- "issn": "1878-5883",
- "date": "2024-04-03",
- "abstract": "Neuronal intranuclear inclusion disease, caused by a GGC repeat expansion in the 5'-untranslated region of NOTCH2NLC, is a rare neurodegenerative condition with highly variable clinical manifestations. In recent years, the number of reported cases have increased dramatically in East Asia. We report the first four genetically confirmed cases of neuronal intranuclear inclusion disease in New Zealand, all having Polynesian ancestry (three New Zealand M\u0101ori and one Cook Island M\u0101ori). Phenotypically, they resemble cases reported from recent large East Asian cohorts.",
+ "publisher": "Neurology",
+ "issn": "0028-3878",
+ "date": "2001-02-13",
+ "abstract": "To characterize the clinical and neuroradiologic features of a new spinocerebellar ataxia, SCA-12, in the index family.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38579412"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11171892"
},
{
- "id": "pmid:38477063",
+ "id": "pmid:35585119",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/38477063",
- "title": "The predominance of \"astrocytic\" intranuclear inclusions in neuronal intranuclear inclusion disease manifesting encephalopathy-like symptoms: A case series with brain biopsy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/35585119",
+ "title": "Prion protein gene mutation detection using long-read Nanopore sequencing.",
"type": "article-journal",
- "doi": "10.1111/neup.12971",
+ "doi": "10.1038/s41598-022-12130-7",
"authors": [
- ["Keisuke", "Ishizawa"],
- ["Takashi", "Komori"],
- ["Taku", "Homma"],
- ["Jun", "Sone"],
- ["Yasuhiro", "Nakata"],
- ["Yoshihiko", "Nakazato"],
- ["Kazushi", "Takahashi"],
- ["Toshimasa", "Yamamoto"],
- ["Atsushi", "Sasaki"]
+ ["Fran\u00e7ois", "Kroll"],
+ ["Athanasios", "Dimitriadis"],
+ ["Tracy", "Campbell"],
+ ["Lee", "Darwent"],
+ ["John", "Collinge"],
+ ["Simon", "Mead"],
+ ["Emmanuelle", "Vire"]
],
- "publisher": "Neuropathology : official journal of the Japanese Society of Neuropathology",
- "issn": "1440-1789",
- "date": "2024-03-13",
- "abstract": "Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder represented by eosinophilic intranuclear inclusions (EIIs) and GGC/CGG repeat expansion in the NOTCH2NLC gene. We report here two adult cases of NIID, genetically confirmed, with manifestation of encephalopathy-like symptoms and address the histopathologic findings obtained by brain biopsies, with a focus on \"astrocytic\" intranuclear inclusions (AIIs). Case 1 presented with paroxysmal restlessness, vertigo, or fever and was later involved in severe dementia and tetraparesis. Case 2 presented with forgetfulness and then with paroxysmal fever and headache. In both cases, delimited areas with gadolinium enhancement on magnetic resonance imaging and corresponding hyperperfusion were detected, leading to brain biopsies of the cortex. On histology, Case 1 showed an abnormal lamination, where the thickness of layers was different from usual. Both neurons and astrocytes showed some dysmorphologic features. Notably, astrocytes rather than neurons harbored EIIs. Case 2 showed a cortex, where neurons tended to be arrayed in a columnar fashion. Astrocytes showed some dysmorphologic features. Notably, much more astrocytes than neurons harbored EIIs. By a double-labeling immunofluorescence study for p62/NeuN and p62/glial fibrillary acidic protein, the predominance of AIIs was confirmed in both cases. Considering the physiological functions of astrocytes for the development and maintenance of the cortex, the encephalopathy-like symptoms, dynamic change of cerebral blood flow, and cortical dysmorphology can reasonably be explained by the dysfunction of EII-bearing astrocytes rather than EII-bearing neurons. This study suggests the presence of a subtype of NIID where AIIs rather than \"neuronal\" intranuclear inclusions are likely a key player in the pathogenesis of NIID, particularly in cases with encephalopathy-like symptoms. The importance of AIIs (\"gliopathy\") should be more appreciated in future studies of NIID.",
+ "publisher": "Scientific reports",
+ "issn": "2045-2322",
+ "date": "2022-05-18",
+ "abstract": "Prion diseases are fatal neurodegenerative conditions that affect humans and animals. Rapid and accurate sequencing of the prion gene PRNP is paramount to human prion disease diagnosis and for animal surveillance programmes. Current methods for PRNP genotyping involve sequencing of small fragments within the protein-coding region. The contribution of variants in the non-coding regions of PRNP including large structural changes is poorly understood. Here, we used long-range PCR and Nanopore sequencing to sequence the full length of PRNP, including its regulatory region, in 25 samples from blood and brain of individuals with inherited or sporadic prion diseases. Nanopore sequencing detected the same variants as identified by Sanger sequencing, including repeat expansions/deletions. Nanopore identified additional single-nucleotide variants in the non-coding regions of PRNP, but no novel structural variants were discovered. Finally, we explored somatic mosaicism of PRNP's octapeptide repeat region, which is a hypothetical cause of sporadic prion disease. While we found changes consistent with somatic mutations, we demonstrate that they may have been generated by the PCR. Our study illustrates the accuracy of Nanopore sequencing for rapid and field prion disease diagnosis and highlights the need for single-molecule sequencing methods for the detection of somatic mutations.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38477063"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35585119"
},
{
- "id": "pmid:37975799",
+ "id": "pmid:21686668",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/37975799",
- "title": "GGC expansions in NOTCH2NLC contribute to Parkinson disease and dopaminergic neuron degeneration.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21686668",
+ "title": "De novo seven extra repeat expanded mutation in the PRNP gene in an Italian patient with early onset dementia.",
"type": "article-journal",
- "doi": "10.1111/ene.16145",
+ "doi": "10.1136/bcr.08.2008.0711",
"authors": [
- ["Qiong", "Liu"],
- ["Juan", "Chen"],
- ["Jin", "Xue"],
- ["Xun", "Zhou"],
- ["Yun", "Tian"],
- ["Qiao", "Xiao"],
- ["Wen", "Huang"],
- ["Yongcheng", "Pan"],
- ["Xiaoxia", "Zhou"],
- ["Jian", "Li"],
- ["Yuwen", "Zhao"],
- ["Hongxu", "Pan"],
- ["Yige", "Wang"],
- ["Runcheng", "He"],
- ["Yaqin", "Xiang"],
- ["Tian", "Tu"],
- ["Qian", "Xu"],
- ["Qiying", "Sun"],
- ["Jieqiong", "Tan"],
- ["Xinxiang", "Yan"],
- ["Jinchen", "Li"],
- ["Jifeng", "Guo"],
- ["Lu", "Shen"],
- ["Ranhui", "Duan"],
- ["Beisha", "Tang"],
- ["Zhenhua", "Liu"]
+ ["M", "Cannella"],
+ ["Tiziana", "Martino"],
+ ["Maria", "Simonelli"],
+ ["Andrea", "Ciammola"],
+ ["Roberto", "Gradini"],
+ ["Andrea", "Ciarmiello"],
+ ["Fernando", "Gianfrancesco"],
+ ["Ferdinando", "Squitieri"]
],
- "publisher": "European journal of neurology",
- "issn": "1468-1331",
- "date": "2023-11-17",
- "abstract": "The role of GGC repeat expansions within NOTCH2NLC in Parkinson's disease (PD) and the substantia nigra (SN) dopaminergic neuron remains unclear. Here, we profile the NOTCH2NLC GGC repeat expansions in a large cohort of patients with PD. We also investigate the role of GGC repeat expansions within NOTCH2NLC in the dopaminergic neurodegeneration of SN.",
+ "publisher": "BMJ case reports",
+ "issn": "1757-790X",
+ "date": "2009-02-02",
+ "abstract": "Point and octapeptide repeat (24 bp) insertional mutations in the prion protein gene (PRNP) cause a dominantly transmitted dementia, associated with spongiform degeneration of the brain, astrocytic gliosis and neuronal loss due to cell accumulation of mutated protease resistant prion protein. The octapeptide repeat region lies between codon 51 and 91, and comprises a nonapeptide followed by a tandem repeat containing four copies of an octapeptide. The normal tandem length in healthy individuals is five repeats R1-R2-R2-R3-R4, but mutations can contain up to nine additional extra repeats. Some insight into this genetic mechanism comes from the de novo meiotic insertional extra repeat mutation in PRNP we detected in a patient whose parents had a normal phenotype and a wild-type sequence in the same gene. To our knowledge, this is the first time this condition has been described.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37975799"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21686668"
},
{
- "id": "pmid:37644522",
+ "id": "pmid:19092329",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/37644522",
- "title": "Expression of expanded GGC repeats within NOTCH2NLC causes cardiac dysfunction in mouse models.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19092329",
+ "title": "A patient with Creutzfeldt-Jakob disease with an insertion of 7 octa-repeats in the PRNP gene: molecular characteristics and clinical features.",
"type": "article-journal",
- "doi": "10.1186/s13578-023-01111-6",
+ "doi": "10.1097/maj.0b013e3181643e50",
"authors": [
- ["Yongcheng", "Pan"],
- ["Ying", "Jiang"],
- ["Juan", "Wan"],
- ["Zhengmao", "Hu"],
- ["Hong", "Jiang"],
- ["Lu", "Shen"],
- ["Beisha", "Tang"],
- ["Yun", "Tian"],
- ["Qiong", "Liu"]
+ ["Yan-Jun", "Guo"],
+ ["Xiao-Fan", "Wang"],
+ ["Jun", "Han"],
+ ["Bao-Yun", "Zhang"],
+ ["Wei-Qin", "Zhao"],
+ ["Qi", "Shi"],
+ ["Yan-Zhen", "Wan"],
+ ["Chen", "Gao"],
+ ["Ji-Mei", "Li"],
+ ["De-Xin", "Wang"],
+ ["Xiao-Ping", "Dong"]
],
- "publisher": "Cell & bioscience",
- "issn": "2045-3701",
- "date": "2023-08-29",
- "abstract": "Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder characterized by widespread intranuclear inclusions in the nervous system as well as multiple visceral organs. In 2019, expanded GGC repeats within the 5' untranslated region of the NOTCH2NLC gene was identified as the causative factor. NIID is a heterogeneous disorder with variable clinical manifestations including cognitive impairment, cerebellar ataxia, parkinsonism, paroxysmal symptoms, autonomic dysfunction, and muscle weakness. Although NIID primarily affects the central and peripheral nervous systems, growing evidence suggests potential cardiac abnormalities in NIID. However, the link between expanded GGC repeats within NOTCH2NLC and cardiac dysfunction remains uncertain.",
+ "publisher": "The American journal of the medical sciences",
+ "issn": "0002-9629",
+ "date": "2008-12-01",
+ "abstract": "We evaluated the features of neuropathology, abnormal prion protein (PrP) molecules, and clinical data of a Chinese woman diagnosed with familiar Creutzfeldt-Jakob disease (CJD), having 7 octa-repeats inserted with codon 129 methionine homozygote in the PRNP gene.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37644522"
-},
-{
- "id": "pmid:37365282",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/37365282",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:37365282']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19092329"
},
{
- "id": "pmid:37184590",
+ "id": "pmid:18366654",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/37184590",
- "title": "A comprehensive study of clinicopathological and genetic features of neuronal intranuclear inclusion disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18366654",
+ "title": "Prion protein insertional mutations increase aggregation propensity but not fiber stability.",
"type": "article-journal",
- "doi": "10.1007/s10072-023-06845-2",
+ "doi": "10.1186/1471-2091-9-7",
"authors": [
- ["Minglei", "Liu"],
- ["Yuan", "Gao"],
- ["Yanpeng", "Yuan"],
- ["Xiaojing", "Liu"],
- ["Yangyang", "Wang"],
- ["Lanjun", "Li"],
- ["Xiaoyun", "Zhang"],
- ["Chenyang", "Jiang"],
- ["Qingzhi", "Wang"],
- ["Yanlin", "Wang"],
- ["Changhe", "Shi"],
- ["Yuming", "Xu"],
- ["Jing", "Yang"]
+ ["Tejas", "Kalastavadi"],
+ ["Heather L", "True"]
],
- "publisher": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology",
- "issn": "1590-3478",
- "date": "2023-05-15",
- "abstract": "The discovery of skin intranuclear inclusions and GGC repeat expansion of NOTCH2NLC has greatly promoted the diagnosis of neuronal intranuclear inclusion disease (NIID). With highly heterogeneous clinical manifestations, NIID patients tend to be underdiagnosed at early stages.",
+ "publisher": "BMC biochemistry",
+ "issn": "1471-2091",
+ "date": "2008-03-17",
+ "abstract": "Mutations in the PRNP gene account for ~15% of all prion disease cases. Little is understood about the mechanism of how some of these mutations in PRNP cause the protein to aggregate into amyloid fibers or cause disease. We have taken advantage of a chimeric protein system to study the oligopeptide repeat domain (ORD) expansions of the prion protein, PrP, and their effect on protein aggregation and amyloid fiber formation. We replaced the ORD of the yeast prion protein Sup35p with that from wild type and expanded ORDs of PrP and compared their biochemical properties in vitro. We previously determined that these chimeric proteins maintain the [PSI+] yeast prion phenotype in vivo. Interestingly, we noted that the repeat expanded chimeric prions seemed to be able to maintain a stronger strain of [PSI+] and convert from [psi-] to [PSI+] with a much higher frequency. In this study we have attempted to understand the biochemical properties of these chimeric proteins and to establish a system to study the properties of the ORD of PrP both in vivo and in vitro.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37184590"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18366654"
},
{
- "id": "pmid:37131242",
+ "id": "pmid:14729275",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/37131242",
- "title": "NOTCH2NLC GGC repeat expansion causes retinal pathology with intranuclear inclusions throughout the retina and causes visual impairment.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/14729275",
+ "title": "A processed pseudogene contributes to apparent mule deer prion gene heterogeneity.",
"type": "article-journal",
- "doi": "10.1186/s40478-023-01564-3",
+ "doi": "10.1016/j.gene.2003.10.022",
"authors": [
- ["Jun", "Sone"],
- ["Shinji", "Ueno"],
- ["Akio", "Akagi"],
- ["Hiroaki", "Miyahara"],
- ["Chisato", "Tamai"],
- ["Yuichi", "Riku"],
- ["Hiroyuki", "Yabata"],
- ["Ryuichi", "Koizumi"],
- ["Tomohiro", "Hattori"],
- ["Hiroshi", "Hirose"],
- ["Yoshito", "Koyanagi"],
- ["Rei", "Kobayashi"],
- ["Hisashi", "Okada"],
- ["Yoshiyuki", "Kishimoto"],
- ["Yoshio", "Hashizume"],
- ["Gen", "Sobue"],
- ["Mari", "Yoshida"],
- ["Yasushi", "Iwasaki"]
+ ["Kelly A", "Brayton"],
+ ["Katherine I", "O'Rourke"],
+ ["Amy K", "Lyda"],
+ ["Michael W", "Miller"],
+ ["Donald P", "Knowles"]
],
- "publisher": "Acta neuropathologica communications",
- "issn": "2051-5960",
- "date": "2023-05-02",
- "abstract": "The retinal pathology of genetically confirmed neuronal intranuclear inclusion disease (NIID) is yet unknown. We report the ocular findings in four NIID patients with NOTCH2NLC GGC repeat expansion to investigate the pathology of retinopathy. All four NIID patients were diagnosed by skin biopsy and NOTCH2NLC GGC repeat analysis. Ocular findings in patients with NIID were studied using fundus photographs, optical coherence tomographic images (OCT), and full-field electroretinograms (ERGs). The histopathology of the retina was studied on autopsy samples from two cases with immunohistochemistry. All patients had an expansion of the GGC repeat (87-134 repeats) in the NOTCH2NLC. Two patients were legally blind and had been diagnosed with retinitis pigmentosa prior to the diagnosis of NIID and assessed with whole exome sequencing to rule out comorbidity with other retinal diseases. Fundus photographs around the posterior pole showed chorioretinal atrophy in the peripapillary regions. OCT showed thinning of the retina. ERGs showed various abnormalities in cases. The histopathology of autopsy samples showed diffusely scattered intranuclear inclusions throughout the retina from the retinal pigment epithelium to the ganglion cell layer, and optic nerve glial cells. And severe gliosis was observed in retina and optic nerve. The NOTCH2NLC GGC repeat expansion causes numerous intranuclear inclusions in the retina and optic nerve cells and gliosis. Visual dysfunction could be the first sign of NIID. We should consider NIID as one of the causes of retinal dystrophy and investigate the GGC repeat expansion in NOTCH2NLC.",
+ "publisher": "Gene",
+ "issn": "0378-1119",
+ "date": "2004-02-04",
+ "abstract": "Pathogenesis and transmission of the prion disorders (transmissible spongiform encephalopathies, TSEs) are mediated by a modified isoform of the prion protein (PrP). Prion protein gene (PRNP) alleles associated with relative susceptibility to TSE have been identified in sheep, humans and possibly elk. Comparable data have not been derived for mule deer, a species susceptible to the TSE chronic wasting disease (CWD). Initial analysis of the open reading frame (ORF) in exon 3 of the mule deer PRNP gene revealed polymorphisms in all 145 samples analyzed, with 10 potential polymorphic sites. Because 144/145 (99.3%) of the samples were heterozygous for a coding change (N/S) at codon 138 (bp 412) and a non-coding polymorphism at bp 418, and individual deer with three or four different alleles were identified a possible gene duplication was indicated. Analysis of BAC clones containing mule deer PRNP genes revealed a full length functional gene and a processed pseudogene. The pseudogene was characteristic of previously described retroelements, in that it lacks introns and is flanked by repeat sequences. Three alleles of the functional gene were identified, with coding changes only at codons 20 (D/G) and 225 (S/F). Determination of PRNP functional gene alleles from 47 CWD-positive mule deer showed the predominant allele encoded 20D225S (frequency 0.85). When alleles were grouped by coding changes in the functional gene, four of the six possible peptide combinations were identified in infected deer. Three pseudogene alleles with coding changes in exon 3 were identified in the mule deer samples examined. Because the TSEs appear to be \"protein only\" disorders, the presence of an untranslated pseudogene is not expected to affect disease resistance. Therefore, selection of a genotyping method specific for the functional gene is critical for large-scale studies to identify the role of the PRNP gene in susceptibility to CWD in mule deer.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37131242"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:14729275"
},
{
- "id": "pmid:37001413",
+ "id": "pmid:9710033",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/37001413",
- "title": "Clinical, radiological, and molecular analyses of neuronal intranuclear inclusion disease with polyglycine inclusions.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9710033",
+ "title": "APOE in non-Alzheimer amyloidoses: transmissible spongiform encephalopathies.",
"type": "article-journal",
- "doi": "10.1016/j.jns.2023.120618",
+ "doi": "10.1212/wnl.51.2.548",
"authors": [
- ["Minori", "Furuta"],
- ["Masayuki", "Sato"],
- ["Hiroo", "Kasahara"],
- ["Setsuki", "Tsukagoshi"],
- ["Kimitoshi", "Hirayanagi"],
- ["Yukio", "Fujita"],
- ["Eriko", "Takai"],
- ["Yuko", "Aihara"],
- ["Koichi", "Okamoto"],
- ["Yoshio", "Ikeda"]
+ ["J", "Chapman"],
+ ["L", "Cerven\u00e1kov\u00e1"],
+ ["R B", "Petersen"],
+ ["H S", "Lee"],
+ ["J", "Estupinan"],
+ ["S", "Richardson"],
+ ["C L", "Vnencak-Jones"],
+ ["D C", "Gajdusek"],
+ ["A D", "Korczyn"],
+ ["P", "Brown"],
+ ["L G", "Goldfarb"]
],
- "publisher": "Journal of the neurological sciences",
- "issn": "1878-5883",
- "date": "2023-03-22",
- "abstract": "Neuronal intranuclear inclusion disease (NIID) is a clinically complex neurological disorder that appears sporadically or autosomally. Expansions of intronic GGC trinucleotide repeats in the NOTCH2 N-terminal-like C (NOTCH2NLC) gene cause NIID. In this study, to clarify the clinical characteristics useful for the differential diagnosis of NIID, clinical data of neurological examination, neuroimaging, and nerve conduction studies of six NIID patients diagnosed by pathological or genetic investigations were analyzed. Clinically useful characteristics for diagnosing NIID include general hyporeflexia, episodic disturbance of consciousness, sensory disturbance, miosis, and dementia. Furthermore, neuroimaging findings, such as leukoencephalopathy in T2-weighted magnetic resonance imaging and a linear high intensity of subcortical U-fibers in diffusion-weighted imaging (DWI), as well as decreased motor nerve conduction velocity, are especially important biomarkers for NIID. However, it is necessary to remember that these features may not always be present, as shown in one of the cases who did not have a DWI abnormality in this study. This study also investigated whether expanded GGC repeats were translated into polyglycine. Immunohistochemical analysis using a custom antibody raised against putative C-terminal polypeptides followed by polyglycine of uN2CpolyG revealed that polyglycines were localized in the intranuclear inclusions in skin biopsy specimens from all six patients, suggesting its involvement in the pathogenesis of NIID.",
+ "publisher": "Neurology",
+ "issn": "0028-3878",
+ "date": "1998-08-01",
+ "abstract": "The APOE genotype has been shown to influence the risk of developing sporadic and familial AD. This effect is isoform-dependent, the APOE epsilon4 allele increasing susceptibility and the APOE epsilon2 allele providing protection. Amyloid formation is an important part of the pathogenesis in AD as well as in spongiform encephalopathies; apoE deposition in amyloid plaques has been documented in both conditions.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37001413"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9710033"
},
{
- "id": "pmid:36809423",
+ "id": "pmid:9565627",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/36809423",
- "title": "Autonomic dysfunction-dominant phenotype in a Chinese family with biallelic GGC repeat expansions in NOTCH2NLC.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9565627",
+ "title": "Abnormal properties of prion protein with insertional mutations in different cell types.",
"type": "article-journal",
- "doi": "10.1007/s10072-023-06688-x",
+ "doi": "10.1074/jbc.273.19.11980",
"authors": [
- ["Bin", "Chen"],
- ["Jing", "Jing"],
- ["Gehong", "Dong"],
- ["Yuzhi", "Shi"],
- ["Cuiping", "Zhang"],
- ["Yumei", "Zhang"],
- ["An", "Wang"],
- ["Hongfei", "Tai"],
- ["Songtao", "Niu"],
- ["Xingao", "Wang"],
- ["Hua", "Pan"],
- ["Zaiqiang", "Zhang"]
+ ["S A", "Priola"],
+ ["B", "Chesebro"]
],
- "publisher": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology",
- "issn": "1590-3478",
- "date": "2023-02-21",
- "abstract": "The GGC repeat expansions in the NOTCH2NLC gene are associated with multiple neurodegenerative disorders. Herein, we report the clinical phenotype in a family with biallelic GGC expansions in NOTCH2NLC. Autonomic dysfunction was a prominent clinical manifestation in three genetically confirmed patients without dementia, parkinsonism, and cerebellar ataxia for\u2009>\u200912\u00a0years. A 7-T brain magnetic resonance imaging in two patients revealed a change in the small cerebral veins. The biallelic GGC repeat expansions may not modify the disease progression in neuronal intranuclear inclusion disease. Autonomic dysfunction-dominant may expand the clinical phenotype of NOTCH2NLC.",
+ "publisher": "The Journal of biological chemistry",
+ "issn": "0021-9258",
+ "date": "1998-05-08",
+ "abstract": "Inherited forms of the human transmissible spongiform encephalopathy Creutzfeldt-Jakob disease (CJD) have been associated with mutations in the normal soluble, protease-sensitive form of the host prion protein (PrP-sen). Normal PrP protein contains five copies of a repeating eight-amino acid region, and PrP molecules with six or more copies of this region are associated with disease in familial CJD. It has been hypothesized that these mutations might facilitate spontaneous formation of the abnormal, aggregated protease-resistant PrP isoform, PrP-res, associated with clinical CJD and other transmissible spongiform encephalopathies (TSE). In the present experiments, hamster PrP molecules with 5 (wild-type), 7, 9, or 11 copies of this repeat region were generated and expressed in mouse fibroblast cells or mouse neuroblastoma cells. In mouse fibroblast cells, mutant hamster PrP molecules expressing 7, 9, and 11 copies of the octapeptide repeat sequence showed altered cell surface expression, but both mutant and wild-type hamster PrP-sen molecules demonstrated abnormal properties of aggregation and increased protease resistance. By contrast in mouse neuroblastoma cells, hamster PrP-sen with 5, 9, and 11 octapeptide repeats were expressed normally on the cell surface, but only PrP-sen molecules with 9 or 11 copies of the repeat motif had abnormal properties of aggregation and increased protease resistance. Overall, regardless of cell type, hamster PrP molecules with greater than 7 octapeptide repeats were more aggregated and more protease-resistant than molecules with 7 repeats or less. However, these abnormal molecules were at least 1000-fold less protease-resistant than bona fide PrP-res derived from TSE-infected brain tissue, and they showed no increased ability to form PrP-res in a cell-free system.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36809423"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9565627"
},
{
- "id": "pmid:36715780",
+ "id": "pmid:33186760",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/36715780",
- "title": "Neuronal intranuclear inclusion disease mimicking progressive supranuclear palsy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/33186760",
+ "title": "Digestive involvement in a severe form of Snyder-Robinson syndrome: Possible expansion of the phenotype.",
"type": "article-journal",
- "doi": "10.1007/s10072-023-06644-9",
+ "doi": "10.1016/j.ejmg.2020.104097",
"authors": [
- ["Min", "Tian"],
- ["Yinlian", "Han"],
- ["Yiqing", "Bi"],
- ["Bohan", "Zhang"],
- ["Ruonan", "Duan"],
- ["Chengyuan", "Song"],
- ["Yiming", "Liu"]
+ ["Pauline", "Dontaine"],
+ ["Elisa", "Kottos"],
+ ["Martine", "Dassonville"],
+ ["Ovidiu", "Balasel"],
+ ["V\u00e9ronique", "Catros"],
+ ["Julie", "Soblet"],
+ ["Pascale", "Perlot"],
+ ["Catheline", "Vilain"]
],
- "publisher": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology",
- "issn": "1590-3478",
- "date": "2023-01-30",
- "abstract": "Given the variable nature of clinical manifestations, neuronal intranuclear inclusion disease (NIID) is regarded as a heterogeneous disease which is challenging to diagnose early. To the present, progressive supranuclear palsy (PSP)-like symptoms have never been listed in the performance of NIID.",
+ "publisher": "European journal of medical genetics",
+ "issn": "1878-0849",
+ "date": "2020-11-10",
+ "abstract": "Snyder-Robinson syndrome (OMIM #309583) is a rare X-linked condition, caused by mutation in the SMS gene (MIM *300105), characterized by a wide spectrum of clinical signs including developmental delay, epilepsy, asthenic habitus, dysmorphism, osteopenia, and renal or genital anomalies. Here we describe two maternal half-brothers who both presented with severe neurodevelopmental delay, seizures, hearing loss, facial dysmorphism, renal and ophthalmologic anomalies, failure to thrive and premature death. A novel p.(Gly203Asp) variant was found at the hemizygous state in the two boys, and an elevated Spermidine/Spermine ratio confirmed the diagnosis of Snyder-Robinson syndrome. One of the brothers presented with gastrointestinal symptoms, with jejunal stenosis, enteral feeding intolerance, failure to thrive due to a dysfunctional gastrointestinal system, cholestasis and exocrine pancreatic insufficiency. Although more studies will be needed to understand its mechanisms, this observation lends further support to the possibility of severe digestive involvement in Snyder Robinson syndrome.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36715780"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33186760"
},
{
- "id": "pmid:36672065",
+ "id": "pmid:32283749",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/36672065",
- "title": "Intermediate-Length GGC Repeat Expansion in NOTCH2NLC Was Identified in Chinese Patients with Amyotrophic Lateral Sclerosis.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/32283749",
+ "title": "Expansion and Conservation of Biosynthetic Gene Clusters in Pathogenic",
"type": "article-journal",
- "doi": "10.3390/brainsci13010085",
+ "doi": "10.3390/toxins12040242",
"authors": [
- ["Mengxia", "Wan"],
- ["Ji", "He"],
- ["Junyan", "Huo"],
- ["Can", "Sun"],
- ["Yu", "Fu"],
- ["Dongsheng", "Fan"]
+ ["Paula M", "Moolhuijzen"],
+ ["Mariano Jordi", "Muria-Gonzalez"],
+ ["Robert", "Syme"],
+ ["Catherine", "Rawlinson"],
+ ["Pao Theen", "See"],
+ ["Caroline S", "Moffat"],
+ ["Simon R", "Ellwood"]
],
- "publisher": "Brain sciences",
- "issn": "2076-3425",
- "date": "2023-01-01",
- "abstract": "GGC repeat expansions in the 5' untranslated region (5'UTR) of the Notch Homolog 2 N-terminal-like C gene (",
+ "publisher": "Toxins",
+ "issn": "2072-6651",
+ "date": "2020-04-09",
+ "abstract": "",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36672065"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32283749"
},
{
- "id": "pmid:36545534",
+ "id": "pmid:30622881",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/36545534",
- "title": "Clinical characteristics of two patients with neuronal intranuclear inclusion disease and literature review.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30622881",
+ "title": "Comparative genomics of",
"type": "article-journal",
- "doi": "10.3389/fnins.2022.1056261",
+ "doi": "10.5598/imafungus.2018.09.02.02",
"authors": [
- ["Bo", "Zhao"],
- ["Miao", "Yang"],
- ["Zhiwei", "Wang"],
- ["Qiqiong", "Yang"],
- ["Yimo", "Zhang"],
- ["Xiaokun", "Qi"],
- ["Shuyi", "Pan"],
- ["Yingxin", "Yu"]
+ ["Bo", "Wang"],
+ ["Xiaofei", "Liang"],
+ ["Mark L", "Gleason"],
+ ["Rong", "Zhang"],
+ ["Guangyu", "Sun"]
],
- "publisher": "Frontiers in neuroscience",
- "issn": "1662-4548",
- "date": "2022-12-05",
- "abstract": "Neuronal intranuclear inclusion disease (NIID) is a rare chronic progressive neurodegenerative disease, with complex and diverse clinical manifestations and pathological eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous systems and visceral organs. Improvements in diagnostic methods such as skin biopsy and gene testing are helpful in revealing the clinical and genetic characters of NIID.",
+ "publisher": "IMA fungus",
+ "issn": "2210-6340",
+ "date": "2018-08-20",
+ "abstract": "Ring rot, one of the most destructive diseases of apple worldwide, is caused primarily by",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36545534"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30622881"
},
{
- "id": "pmid:36483830",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/36483830",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:36483830']' timed out after 3 seconds"
+ "id": "pmid:25663198",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25663198",
+ "title": "Derivation, Expansion, and Motor Neuron Differentiation of Human-Induced Pluripotent Stem Cells with Non-Integrating Episomal Vectors and a Defined Xenogeneic-free Culture System.",
+ "type": "article-journal",
+ "doi": "10.1007/s12035-014-9084-z",
+ "authors": [
+ ["Wentao", "Hu"],
+ ["Yongpei", "He"],
+ ["Yongjie", "Xiong"],
+ ["Hong", "Lu"],
+ ["Hong", "Chen"],
+ ["Limin", "Hou"],
+ ["Zhandong", "Qiu"],
+ ["Yu", "Fang"],
+ ["Suming", "Zhang"]
+ ],
+ "publisher": "Molecular neurobiology",
+ "issn": "1559-1182",
+ "date": "2015-02-10",
+ "abstract": "Induced pluripotent stem cells (iPSCs) generated from patient-derived somatic cells provides the opportunity for model development in order to study patient-specific disease states with the potential for drug discovery. However, use of lentivirus and exposure of iPSCs to animal-derived products limit their therapeutic utility and affect lineage differentiation and subsequent downstream functionality of iPSC derivatives. Within the context of this study, we describe a simple and practical protocol enabling the efficient reprogramming of terminally differentiated adult fibroblasts into integration-free human iPSCs (hiPSCs) using a combination of episomal plasmids with small molecules (SMs). Using this approach, there was a 10-fold increase in reprogramming efficiency over single plasmid vector-based methods. We obtained approximately 100 iPSCs colonies from 1\u2009\u00d7\u200910(5) human adult dermal fibroblasts (HADFs) and achieved approximately 0.1% reprogramming efficiencies. Concurrently, we developed a highly conducive culture system using xeno-free media and human vitronectin. The resulting hiPSCs were free of DNA integration and had completely lost episomal vectors, maintained long-term self-renewal, featured a normal karyotype, expressed pluripotent stem cell markers, and possessed the capability of differentiating into components of all three germ layers in vivo. Finally, we demonstrate that the integration-free hiPSCs could be differentiated into motor neurons under xeno-free culture conditions. This induction method will promote the derivation of patient-specific integration-free and xeno-free iPSCs and improve the strategy for motor neuron derivation. Our approach provides a useful tool for human disease models, drug screen, and clinical applications.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25663198"
},
{
- "id": "pmid:36458450",
+ "id": "pmid:15148657",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/36458450",
- "title": "Neuropathological features of adult-onset neuronal intranuclear inclusion disease with fluid-attenuated inversion recovery high-intensity signals in the cerebellar paravermal area from an early stage: A case report.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15148657",
+ "title": "Uncommon deletions of the Smith-Magenis syndrome region can be recurrent when alternate low-copy repeats act as homologous recombination substrates.",
"type": "article-journal",
- "doi": "10.5414/np301499",
+ "doi": "10.1086/422016",
"authors": [
- ["Taku", "Homma"],
- ["Utako", "Nagaoka"],
- ["Yasuhiro", "Nakata"],
- ["Jun", "Sone"],
- ["Asuka", "Funai"],
- ["Aki", "Murayama"],
- ["Cisato", "Tamai"],
- ["Takashi", "Komori"],
- ["Kazushi", "Takahashi"]
+ ["Christine J", "Shaw"],
+ ["Marjorie A", "Withers"],
+ ["James R", "Lupski"]
],
- "publisher": "Clinical neuropathology",
- "issn": "0722-5091",
- "date": "2023-01-01",
- "abstract": "Neuronal intranuclear inclusion disease (NIID) is a neurological disorder characterized by eosinophilic intranuclear inclusions (INI) in systemic organs and various cell types. High-intensity signals along the corticomedullary junction on diffusion-weighted imaging and presence of cellular p62-INI in skin biopsy are known indicators for NIID. Furthermore, GGC repeat expansion in",
+ "publisher": "American journal of human genetics",
+ "issn": "0002-9297",
+ "date": "2004-05-13",
+ "abstract": "Several homologous recombination \"hotspots,\" or sites of positional preference for strand exchanges, associated with recurrent deletions and duplications have been reported within large low-copy repeats (LCRs). Recently, such a hotspot was identified in patients with the Smith-Magenis syndrome (SMS) common deletion of approximately 4 Mb or a reciprocal duplication within the KER gene cluster of the SMS-REP LCRs, in which 50% of analyzed strand exchanges resulting in deletion and 23% of those resulting in duplication occurred. Here, we report an additional recombination hotspot within LCR17pA and LCR17pD, which serve as alternative substrates for nonallelic homologous recombination that results in large (approximately 5 Mb) deletions of 17p11.2, which include the SMS region. Using polymerase-chain-reaction mapping of somatic cell hybrid lines, we refined the breakpoints of six deletions within these LCRs. Sequence analysis of the recombinant junctions revealed that all six strand exchanges occurred within a 524-bp interval, and four of them occurred within an AluSq/x element. This interval represents only 0.5% of the 124-kb stretch of 98.6% sequence identity between LCR17pA and LCR17pD. A search for potentially stimulating sequence motifs revealed short AT-rich segments flanking the recombination hotspot. Our findings indicate that alternative LCRs can mediate rearrangements, resulting in haploinsufficiency of the SMS critical region, and reimplicate homologous recombination as a major mechanism for genomic disorders.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36458450"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15148657"
},
{
- "id": "pmid:36207023",
+ "id": "pmid:8817239",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/36207023",
- "title": "",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/8817239",
+ "title": "Nuclear protein binding and functional activity of a variant insulin gene found in non-insulin-dependent diabetes mellitus.",
"type": "article-journal",
- "doi": "10.1136/svn-2022-001631",
+ "doi": "10.1055/s-0029-1211446",
"authors": [
- ["Yun-Chao", "Wang"],
- ["Yu", "Fan"],
- ["Wen-Kai", "Yu"],
- ["Si", "Shen"],
- ["Jia-Di", "Li"],
- ["Yuan", "Gao"],
- ["Yan", "Ji"],
- ["Yu-Sheng", "Li"],
- ["Lu-Lu", "Yu"],
- ["Zi-Chen", "Zhao"],
- ["Shan-Shan", "Li"],
- ["Yao", "Ding"],
- ["Chang-He", "Shi"],
- ["Yu-Ming", "Xu"]
+ ["N", "Yildiz"],
+ ["T", "Diedrich"],
+ ["W", "Knepel"]
],
- "publisher": "Stroke and vascular neurology",
- "issn": "2059-8696",
- "date": "2022-10-07",
- "abstract": "GGC repeat expansions in the human-specific",
+ "publisher": "Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association",
+ "issn": "0947-7349",
+ "date": "1996-01-01",
+ "abstract": "In a subset of patients with non-insulin-dependent diabetes mellitus an 8-base pair (bp) repeat was found from -322 to -315 in the 5'-flanking region of the insulin gene. This 8-bp repeat is inserted into a sequence that is highly homologous to a sequence motif, called PISCES (pancreatic islet cell-specific enhancer sequences), found within cell-specific enhancer elements of the rat insulin I (Ins-E1, from -332 to -285), rat glucagon (Glu-G3) and rat somatostatin (SMS-UE) genes. The PISCES motif confers pancreatic islet-specific activity and is recognized by an islet-specific transcription factor (PISCES-BP). The consequences on functional activity and on protein binding of the 8-bp repeat sequence in the human insulin promoter was investigated. When fused to a reporter gene and transiently transfected into an insulin-producing islet cell line, the 8-bp repeat decreased basal transcriptional activity of the human insulin promoter (from -366 to +42) whereas the induction of promoter activity by cAMP was unaffected. The isolated rat Ins-E1 element was sufficient to confer basal transcriptional activity to a minimal promoter; the corresponding fragments of the normal and variant human insulin genes (from -329 to -288), however, were not. Using nuclear extracts in an electrophoretic mobility shift assay, it was found that PISCES-BP recognizes rat Ins-E1, but PISCES-BP binding to the corresponding normal and variant human insulin promoter fragments was not detectable and weak, respectively. However, a nuclear protein was found that binds to the variant but not normal human sequence. These data suggest that the 8-bp repeat in the variant human insulin promoter found in patients with non-insulin-dependent diabetes mellitus allows the binding of a nuclear protein that interferes with promoter function.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36207023"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8817239"
},
{
- "id": "pmid:36191230",
+ "id": "pmid:31483537",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/36191230",
- "title": "CGG repeat expansion in",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/31483537",
+ "title": "Intronic (TTTGA)",
"type": "article-journal",
- "doi": "10.1073/pnas.2208649119",
+ "doi": "10.1002/mds.27832",
"authors": [
- ["Jiaxi", "Yu"],
- ["Tongling", "Liufu"],
- ["Yilei", "Zheng"],
- ["Jin", "Xu"],
- ["Lingchao", "Meng"],
- ["Wei", "Zhang"],
- ["Yun", "Yuan"],
- ["Daojun", "Hong"],
- ["Nicolas", "Charlet-Berguerand"],
- ["Zhaoxia", "Wang"],
- ["Jianwen", "Deng"]
+ ["Zhidong", "Cen"],
+ ["You", "Chen"],
+ ["Dehao", "Yang"],
+ ["Qingchen", "Zhu"],
+ ["Si", "Chen"],
+ ["Xinhui", "Chen"],
+ ["Bo", "Wang"],
+ ["Fei", "Xie"],
+ ["Zhiyuan", "Ouyang"],
+ ["Zhengwen", "Jiang"],
+ ["Aisi", "Fu"],
+ ["Ben", "Hu"],
+ ["Houmin", "Yin"],
+ ["Xia", "Qiu"],
+ ["Feng", "Yu"],
+ ["Xiaoping", "Du"],
+ ["Weicheng", "Hao"],
+ ["Yuxi", "Liu"],
+ ["Haotian", "Wang"],
+ ["Lebo", "Wang"],
+ ["Xiafei", "Yu"],
+ ["Yichuan", "Xiao"],
+ ["Chunyu", "Liu"],
+ ["Jianfeng", "Xiao"],
+ ["Yongxing", "Zhou"],
+ ["Wei", "Yang"],
+ ["Baorong", "Zhang"],
+ ["Wei", "Luo"]
],
- "publisher": "Proceedings of the National Academy of Sciences of the United States of America",
- "issn": "1091-6490",
- "date": "2022-10-03",
- "abstract": "Neuronal intranuclear inclusion disease (NIID) is a neuromuscular/neurodegenerative disease caused by the expansion of CGG repeats in the 5' untranslated region (UTR) of the",
+ "publisher": "Movement disorders : official journal of the Movement Disorder Society",
+ "issn": "1531-8257",
+ "date": "2019-09-04",
+ "abstract": "Intronic (TTTCA)",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36191230"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31483537"
},
{
- "id": "pmid:36172483",
+ "id": "pmid:40481300",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/36172483",
- "title": "Urine cytological study in patients with clinicopathologically confirmed neuronal intranuclear inclusion disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/40481300",
+ "title": "Comprehensive Characterisation of the RFC1 Repeat in an Australian Cohort.",
"type": "article-journal",
- "doi": "10.3389/fnagi.2022.977604",
+ "doi": "10.1007/s12311-025-01867-2",
"authors": [
- ["Yiyi", "Zhou"],
- ["Pengcheng", "Huang"],
- ["Zhaojun", "Huang"],
- ["Yun", "Peng"],
- ["Yilei", "Zheng"],
- ["Yaqing", "Yu"],
- ["Min", "Zhu"],
- ["Jianwen", "Deng"],
- ["Zhaoxia", "Wang"],
- ["Daojun", "Hong"]
+ ["Kayli C", "Davies"],
+ ["Haloom", "Rafehi"],
+ ["Liam G", "Fearnley"],
+ ["Penny", "Snell"],
+ ["Greta", "Gillies"],
+ ["Tess A", "Field"],
+ ["G\u00e1bor M", "Halm\u00e1gyi"],
+ ["Kishore R", "Kumar"],
+ ["Kate", "Pope"],
+ ["Renee", "Smyth"],
+ ["Susan E", "Tomlinson"],
+ ["Stephen", "Tisch"],
+ ["Chi-Chang", "Tang"],
+ ["Shaun R D", "Watson"],
+ ["Thomas", "Wellings"],
+ ["Kathy H C", "Wu"],
+ ["David J", "Szmulewicz"],
+ ["Martin B", "Delatycki"],
+ ["Melanie", "Bahlo"],
+ ["Paul J", "Lockhart"]
],
- "publisher": "Frontiers in aging neuroscience",
- "issn": "1663-4365",
- "date": "2022-09-12",
- "abstract": "The diagnosis of neuronal intranuclear inclusion disease (NIID) is currently based on CGG repeat expansion in the 5'UTR of the",
+ "publisher": "Cerebellum (London, England)",
+ "issn": "1473-4230",
+ "date": "2025-06-07",
+ "abstract": "RFC1-related disease, which includes cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), is a late-onset neurodegenerative disorder primarily caused by biallelic AAGGG",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36172483"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40481300"
},
{
- "id": "pmid:36041634",
+ "id": "pmid:40471691",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/36041634",
- "title": "Patients with biallelic GGC repeat expansions in NOTCH2NLC exhibiting a typical neuronal intranuclear inclusion disease phenotype.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/40471691",
+ "title": "Chronic idiopathic axonal neuropathy: antibodies, genetics, and beyond.",
"type": "article-journal",
- "doi": "10.1016/j.ygeno.2022.110469",
+ "doi": "10.1097/wco.0000000000001387",
"authors": [
- ["Shinichi", "Kameyama"],
- ["Takeshi", "Mizuguchi"],
- ["Hiroshi", "Doi"],
- ["Shigeru", "Koyano"],
- ["Masaki", "Okubo"],
- ["Mikiko", "Tada"],
- ["Hiroshi", "Shimizu"],
- ["Hiromi", "Fukuda"],
- ["Naomi", "Tsuchida"],
- ["Yuri", "Uchiyama"],
- ["Eriko", "Koshimizu"],
- ["Kohei", "Hamanaka"],
- ["Atsushi", "Fujita"],
- ["Kazuharu", "Misawa"],
- ["Satoko", "Miyatake"],
- ["Kazuaki", "Kanai"],
- ["Fumiaki", "Tanaka"],
- ["Naomichi", "Matsumoto"]
+ ["Mehmet Can", "Sari"],
+ ["Ahmet", "Hoke"]
],
- "publisher": "Genomics",
- "issn": "1089-8646",
- "date": "2022-08-27",
- "abstract": "We report two patients with autosomal dominant neuronal intranuclear inclusion disease (NIID) harboring the biallelic GGC repeat expansion in NOTCH2NLC to uncover the impact of repeat expansion zygosity on the clinical phenotype. The zygosity of the entire NOTCH2NLC GGC repeat expansion and DNA methylation were comprehensively evaluated using fluorescent amplicon length PCR (AL-PCR), Southern blotting and targeted long-read sequencing, and detailed genetic/epigenetic and clinical features were described. In AL-PCR, we could not recognize the wild-type allele in both patients. Targeted long-read sequencing revealed that one patient harbored a homozygous repeat expansion. The other patient harbored compound heterozygous repeat expansions. The GGC repeats and the nearest CpG island were hypomethylated in all expanded alleles in both patients. Both patients harboring the biallelic GGC repeat expansion showed a typical dementia-dominant NIID phenotype. In conclusion, the biallelic GGC repeat expansion in two typical NIID patients indicated that NOTCH2NLC-related diseases could be completely dominant.",
+ "publisher": "Current opinion in neurology",
+ "issn": "1473-6551",
+ "date": "2025-06-06",
+ "abstract": "Chronic idiopathic axonal neuropathy (CIAP) remains a diagnostic challenge, with many cases historically classified as idiopathic due to the absence of identifiable genetic, metabolic, or immune-mediated causes. This review examines recent advancements in understanding CIAP, focusing on novel genetic mutations, autoantibodies, and metabolic pathways that challenge the \"idiopathic\" designation. Specifically, we highlight sorbitol dehydrogenase (SORD) deficiency and replication factor C subunit 1 (RFC1) repeat expansions, and comment on the controversy surrounding autoantibody-associated small fiber neuropathy (SFN).",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36041634"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40471691"
},
{
- "id": "pmid:36033605",
+ "id": "pmid:40461673",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/36033605",
- "title": "Case report: Adult-onset neuronal intranuclear inclusion disease with an amyotrophic lateral sclerosis phenotype.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/40461673",
+ "title": "Impact of the intronic RFC1 expansion size in CANVAS phenotype: an oculomotor study.",
"type": "article-journal",
- "doi": "10.3389/fnins.2022.960680",
+ "doi": "10.1007/s00415-025-13150-9",
"authors": [
- ["Masako", "Fujita"],
- ["Tatsuya", "Ueno"],
- ["Yasuo", "Miki"],
- ["Akira", "Arai"],
- ["Hidekachi", "Kurotaki"],
- ["Koichi", "Wakabayashi"],
- ["Masahiko", "Tomiyama"]
+ ["Mathieu", "Dupr\u00e9"],
+ ["Ruben", "Hermann"],
+ ["L\u00e9o", "Vidoni"],
+ ["Isabelle", "Quadrio"],
+ ["Philippe", "Latour"],
+ ["Fabien", "Subtil"],
+ ["Caroline", "Froment Tilikete"]
],
- "publisher": "Frontiers in neuroscience",
- "issn": "1662-4548",
- "date": "2022-08-10",
- "abstract": "Amyotrophic lateral sclerosis (ALS) is one of the differential diagnoses of diseases that occur in adulthood and lead to progressive generalized muscle weakness. Neuronal intranuclear inclusion disease (NIID) is a disease in which histopathologically eosinophilic nuclear inclusion bodies are found in various systems. Both familial and sporadic forms of the disease have been reported. Most cases of sporadic NIID are of the dementia type, in which the main symptom is dementia at the first onset. Familial NIID is more diverse, with the main dominant symptoms being muscle weakness (NIID-M), dementia (NIID-D), and parkinsonism (NIID-P). Furthermore, recently, a GGC-repeat expansion in the Notch 2 N-terminal like C (",
+ "publisher": "Journal of neurology",
+ "issn": "1432-1459",
+ "date": "2025-06-03",
+ "abstract": "The identification of the RFC1 homozygous intronic expansion in cerebellar ataxia neuropathy and vestibular areflexia syndrome (CANVAS) highlighted that genetically determined CANVAS patients exhibit a wide range of clinical presentations and natural course. Previous studies suggested a link between disease severity and the size of the intronic expansion. The aim of our study was to obtain quantitative data related to vestibular and cerebellar impairments using oculomotor recordings to provide further evidence of a link between RFC1 intronic expansion size and the phenotype. This study recruited 26 genetically determined CANVAS patients in whom the size of the pathological intronic expansion was measured on both alleles. In addition to clinical data, we also recorded the Overall Neuropathy Limitation Scale (ONLS) and conducted objective oculomotor testing. According to the median expansion length on one allele, the patients were divided in a longer intronic repeat subgroup and a shorter intronic repeat subgroup. Given the homozygous nature of this disease, this analysis was carried out for the smallest and for the longest allele. We found for the smallest allele that vestibular deficit and cerebellar impairment were significantly more frequent and mean ONLS, smooth pursuit, pendular visually enhanced vestibulo-ocular reflex, and head impulse vestibulo-ocular reflex gains were significantly more impaired in the subgroup of patients with the long intronic repeat. This work provides objective evidence for a functional impact of the pathological intronic expansion size in CANVAS and highlights the interest of oculomotor assessment in research and clinical practice both for diagnostic and potentially prognostic purposes.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36033605"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40461673"
},
{
- "id": "pmid:35866887",
+ "id": "pmid:40313272",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/35866887",
- "title": "Profiling the NOTCH2NLC GGC Repeat Expansion in Parkinson's Disease in the European Population.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/40313272",
+ "title": "Heterozygous and Homozygous",
"type": "article-journal",
- "doi": "10.1002/mds.29155",
+ "doi": "10.1101/2025.04.18.25325809",
"authors": [
- ["Kimberley J", "Billingsley"],
- ["Pilar", "Alvarez Jerez"],
- ["Francis P", "Grenn"],
- ["Sara", "Bandres-Ciga"],
- ["Laksh", "Malik"],
- ["Dena", "Hernandez"],
- ["Ali", "Torkamani"],
- ["Mina", "Ryten"],
- ["John", "Hardy"],
- ["Sonja W", "Scholz"],
- ["Bryan J", "Traynor"],
- ["Clifton L", "Dalgard"],
- ["Debra J", "Ehrlich"],
- ["Toshiko", "Tanaka"],
- ["Luigi", "Ferrucci"],
- ["Thomas G", "Beach"],
- ["Geidy E", "Serrano"],
- ["Jinhui", "Ding"],
- ["J Raphael", "Gibbs"],
- ["Cornelis", "Blauwendraat"],
- ["Andrew B", "Singleton"]
+ ["Zitian", "Tang"],
+ ["Sinem S", "Ovunc"],
+ ["Elle", "Mehinovic"],
+ ["Simone", "Thomas"],
+ ["Jenna", "Ulibarri"],
+ ["Zefan", "Li"],
+ ["Dustin", "Baldridge"],
+ ["Carlos", "Cruchaga"],
+ ["Matt", "Johnson"],
+ ["Jeffrey", "Milbrandt"],
+ ["Brian", "Callaghan"],
+ ["Ahmet", "H\u00f6ke"],
+ ["Peter K", "Todd"],
+ ["Sheng Chih", "Jin"]
],
- "publisher": "Movement disorders : official journal of the Movement Disorder Society",
- "issn": "1531-8257",
- "date": "2022-07-22",
- "abstract": "",
+ "publisher": "medRxiv : the preprint server for health sciences",
+ "issn": "",
+ "date": "2025-04-23",
+ "abstract": "Biallelic intronic AAGGG repeat expansions in",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35866887"
-},
-{
- "id": "pmid:35772299",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/35772299",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:35772299']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40313272"
},
{
- "id": "pmid:35419641",
+ "id": "pmid:40211677",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/35419641",
- "title": "Adult-onset autosomal dominant leukodystrophy and neuronal intranuclear inclusion disease: lessons from two new Chinese families.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/40211677",
+ "title": "Genetic and Clinical Features of 10 Families With Hereditary Sensory Neuropathies.",
"type": "article-journal",
- "doi": "10.1007/s10072-022-06057-0",
+ "doi": "10.1111/jns.70020",
"authors": [
- ["Shuai", "Chen"],
- ["Jin-Long", "Zou"],
- ["Shuang", "He"],
- ["Wei", "Li"],
- ["Jie-Wen", "Zhang"],
- ["Shu-Jian", "Li"]
+ ["Ke", "Xu"],
+ ["Zhongzheng", "Li"],
+ ["Mengli", "Wang"],
+ ["Lei", "Liu"],
+ ["Sen", "Zeng"],
+ ["Xiaobo", "Li"],
+ ["Wanqian", "Cao"],
+ ["Shunxiang", "Huang"],
+ ["Huadong", "Zhao"],
+ ["Yan", "Yang"],
+ ["Yongzhi", "Xie"],
+ ["Zhengmao", "Hu"],
+ ["Beisha", "Tang"],
+ ["Ruxu", "Zhang"]
],
- "publisher": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology",
- "issn": "1590-3478",
- "date": "2022-04-14",
- "abstract": "Adult-onset autosomal dominant leukodystrophy (ADLD) is a rare genetic leukoencephalopathy caused by duplication of the lamin B1 gene (LMNB1) or LMNB1 upstream deletions. Neuronal intranuclear inclusion disease (NIID) is another leukoencephalopathy due to GGC repeat expansion in the 5'-untranslated region of the NOTCH2NLC gene. Here, we report two Chinese ADLD families with neuroimaging and clinical features mimicking NIID.",
+ "publisher": "Journal of the peripheral nervous system : JPNS",
+ "issn": "1529-8027",
+ "date": "2025-06-01",
+ "abstract": "Hereditary sensory neuropathies (HSNs) are a group of genetically and clinically heterogeneous diseases. Our study aims to summarize the genetic and clinical features of HSNs in 10 Chinese families.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35419641"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40211677"
},
{
- "id": "pmid:35411397",
+ "id": "pmid:40204545",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/35411397",
- "title": "Neuronal intranuclear inclusion disease in patients with adult-onset non-vascular leukoencephalopathy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/40204545",
+ "title": "Comment on \"Spectrum disorder of RFC1 expansions/CANVAS: Clinical and electrophysiological characterization of a group of 31 patients\".",
"type": "article-journal",
- "doi": "10.1093/brain/awac135",
+ "doi": "10.1016/j.clinph.2025.03.037",
"authors": [
- ["Yi Hong", "Liu"],
- ["Ying Tsen", "Chou"],
- ["Fu Pang", "Chang"],
- ["Wei Ju", "Lee"],
- ["Yuh Cherng", "Guo"],
- ["Cheng Ta", "Chou"],
- ["Hui Chun", "Huang"],
- ["Takeshi", "Mizuguchi"],
- ["Chien Chen", "Chou"],
- ["Hsiang Yu", "Yu"],
- ["Kai Wei", "Yu"],
- ["Hsiu Mei", "Wu"],
- ["Pei Chien", "Tsai"],
- ["Naomichi", "Matsumoto"],
- ["Yi Chung", "Lee"],
- ["Yi Chu", "Liao"]
+ ["Jos\u00e9", "Berciano"],
+ ["Antonio", "Garc\u00eda"],
+ ["Jon", "Infante"]
],
- "publisher": "Brain : a journal of neurology",
- "issn": "1460-2156",
- "date": "2022-09-14",
- "abstract": "Neuronal intranuclear inclusion disease (NIID), caused by an expansion of GGC repeats in the 5'-untranslated region of NOTCH2NLC, is an important but underdiagnosed cause of adult-onset leukoencephalopathies. The present study aimed to investigate the prevalence, clinical spectrum and brain MRI characteristics of NIID in adult-onset nonvascular leukoencephalopathies and assess the diagnostic performance of neuroimaging features. One hundred and sixty-one unrelated Taiwanese patients with genetically undetermined nonvascular leukoencephalopathies were screened for the NOTCH2NLC GGC repeat expansions using fragment analysis, repeat-primed PCR, Southern blot analysis and/or nanopore sequencing with Cas9-mediated enrichment. Among them, 32 (19.9%) patients had an expanded NOTCH2NLC allele and were diagnosed with NIID. We enrolled another two affected family members from one patient for further analysis. The size of the expanded NOTCH2NLC GGC repeats in the 34 patients ranged from 73 to 323 repeats. Skin biopsies from five patients all showed eosinophilic, p62-positive intranuclear inclusions in the sweat gland cells and dermal adipocytes. Among the 34 NIID patients presenting with nonvascular leukoencephalopathies, the median age at symptom onset was 61 years (range, 41-78 years) and the initial presentations included cognitive decline (44.1%; 15/34), acute encephalitis-like episodes (32.4%; 11/34), limb weakness (11.8%; 4/34) and parkinsonism (11.8%; 4/34). Cognitive decline (64.7%; 22/34) and acute encephalitis-like episodes (55.9%; 19/34) were also the most common overall manifestations. Two-thirds of the patients had either bladder dysfunction or visual disturbance. Comparing the brain MRI features between the NIID patients and individuals with other undetermined leukoencephalopathies, corticomedullary junction curvilinear lesions on diffusion weighted images were the best biomarkers for diagnosing NIID with high specificity (98.4%) and sensitivity (88.2%). However, this diffusion weighted imaging abnormality was absent in 11.8% of the NIID patients. When only fluid-attenuated inversion recovery images were available, the presence of white matter hyperintensity lesions either in the paravermis or middle cerebellar peduncles also favoured the diagnosis of NIID with a specificity of 85.3% and sensitivity of 76.5%. Among the MRI scans of 10 patients, performed within 5 days of the onset of acute encephalitis-like episodes, five showed cortical hyperintense lesions on diffusion weighted images and two revealed focal brain oedema. In conclusion, NIID accounts for 19.9% (32/161) of patients with adult-onset genetically undiagnosed nonvascular leukoencephalopathies in Taiwan. Half of the NIID patients developed encephalitis-like episodes with restricted diffusion in the cortical regions on diffusion weighted images at the acute stage. Corticomedullary junction hyperintense lesions, white matter hyperintensities in the paravermis or middle cerebellar peduncles, bladder dysfunction and visual disturbance are useful hints to diagnosing NIID.",
+ "publisher": "Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology",
+ "issn": "1872-8952",
+ "date": "2025-04-05",
+ "abstract": "",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35411397"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40204545"
},
{
- "id": "pmid:35147270",
+ "id": "pmid:39721397",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/35147270",
- "title": "The role of NOTCH2NLC in Parkinson's disease: A clinical, neuroimaging, and pathological study.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/39721397",
+ "title": "Spectrum disorder of RFC1 expansions/CANVAS: Clinical and electrophysiological characterization of a group of 31 patients.",
"type": "article-journal",
- "doi": "10.1111/ene.15283",
+ "doi": "10.1016/j.clinph.2024.12.007",
"authors": [
- ["Peng", "Liu"],
- ["Dehao", "Yang"],
- ["Fan", "Zhang"],
- ["Shuqi", "Chen"],
- ["Fei", "Xie"],
- ["Yong", "Luo"],
- ["Haotian", "Wang"],
- ["Yueting", "Chen"],
- ["Zhiru", "Lin"],
- ["Lebo", "Wang"],
- ["Xinhui", "Chen"],
- ["Bo", "Wang"],
- ["Sheng", "Wu"],
- ["Zhiyuan", "Ouyang"],
- ["Zhidong", "Cen"],
- ["Wei", "Luo"]
+ ["Elena", "Lainez"],
+ ["Daniel", "S\u00e1nchez-Tejerina"],
+ ["Paula", "Fern\u00e1ndez Alvarez"],
+ ["Margarida", "Gratac\u00f2s-Vi\u00f1ola"],
+ ["Jos\u00e9 Luis", "Seoane"],
+ ["Daniela Isabel", "Santa-Cruz"],
+ ["Lena", "Verdaguer"],
+ ["Ra\u00fal", "Juntas"],
+ ["Arnau", "Llaurad\u00f3"],
+ ["Javier", "Sotoca"],
+ ["Maria", "Salvado"],
+ ["Elena", "Garc\u00eda Arumi"],
+ ["N\u00faria", "Raguer"]
],
- "publisher": "European journal of neurology",
- "issn": "1468-1331",
- "date": "2022-03-03",
- "abstract": "Recently, the pathogenic and intermediate GGC repeat expansion in NOTCH2NLC was detected in Parkinson's disease (PD). However, detailed clinical, neuroimaging, and pathological information of clinically diagnosed PD patients with pathogenic GGC repeat expansion in NOTCH2NLC remains scarce. Thus, we aimed to elucidate the clinical, neuroimaging, and pathological characteristics of PD patients carrying the pathogenic GGC repeat expansion in NOTCH2NLC.",
+ "publisher": "Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology",
+ "issn": "1872-8952",
+ "date": "2024-12-19",
+ "abstract": "Biallelic expansion of the pentanucleotide AAGGG in the RFC1- gene is associated with cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). This study aimed to comprehensively characterise this condition by conducting an in-depth neurophysiological examination of afflicted patients.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35147270"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39721397"
},
{
- "id": "pmid:34797461",
+ "id": "pmid:39543176",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/34797461",
- "title": "Characteristics of ocular findings of patients with neuronal intranuclear inclusion disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/39543176",
+ "title": "Elucidating the pathobiology of Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome (CANVAS) with its expanded RNA structure formation and proteinopathy.",
"type": "article-journal",
- "doi": "10.1007/s10072-021-05748-4",
+ "doi": "10.1038/s41598-024-78947-6",
"authors": [
- ["Chang", "Liu"],
- ["Xinghua", "Luan"],
- ["Xiaohong", "Liu"],
- ["Xiangning", "Wang"],
- ["Xuan", "Cai"],
- ["Tingting", "Li"],
- ["Li", "Cao"],
- ["Da", "Long"]
+ ["Krishna", "Singh"],
+ ["Sakshi", "Shukla"],
+ ["Uma", "Shankar"],
+ ["Neha", "Jain"],
+ ["Rishav", "Nag"],
+ ["Kumari Aditi", "Pramod"],
+ ["Amit", "Kumar"]
],
- "publisher": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology",
- "issn": "1590-3478",
- "date": "2021-11-19",
- "abstract": "This study aimed to explore the ocular characteristics of neuronal intranuclear inclusion disease (NIID), caused by GGC repeat expansion in the NOTCH2NLC gene, combined with the systemic clinical manifestations, and propose early diagnostic features of NIID.",
+ "publisher": "Scientific reports",
+ "issn": "2045-2322",
+ "date": "2024-11-14",
+ "abstract": "Numerous neurological disorders are linked to sequences rich in guanine repeats found in introns, exons, and regulatory regions of genes. These sequences have been observed to form stable G-quadruplex (GQ) structures both\u00a0in vitro\u00a0and in vitro.\u00a0Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome (CANVAS), a slowly progressive neurodegenerative disorder, is associated with the biallelic expansion of (AAGGG)",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34797461"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39543176"
},
{
- "id": "pmid:34774111",
+ "id": "pmid:39507594",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/34774111",
- "title": "Father-to-offspring transmission of extremely long NOTCH2NLC repeat expansions with contractions: genetic and epigenetic profiling with long-read sequencing.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/39507594",
+ "title": "Early Peripheral Nerve Involvement at the Time of Coughing in Patients With",
"type": "article-journal",
- "doi": "10.1186/s13148-021-01192-5",
+ "doi": "10.1212/nxg.0000000000200166",
"authors": [
- ["Hiromi", "Fukuda"],
- ["Daisuke", "Yamaguchi"],
- ["Kristofor", "Nyquist"],
- ["Yasushi", "Yabuki"],
- ["Satoko", "Miyatake"],
- ["Yuri", "Uchiyama"],
- ["Kohei", "Hamanaka"],
- ["Ken", "Saida"],
- ["Eriko", "Koshimizu"],
- ["Naomi", "Tsuchida"],
- ["Atsushi", "Fujita"],
- ["Satomi", "Mitsuhashi"],
- ["Kazuyuki", "Ohbo"],
- ["Yuki", "Satake"],
- ["Jun", "Sone"],
- ["Hiroshi", "Doi"],
- ["Keisuke", "Morihara"],
- ["Tomoko", "Okamoto"],
- ["Yuji", "Takahashi"],
- ["Aaron M", "Wenger"],
- ["Norifumi", "Shioda"],
- ["Fumiaki", "Tanaka"],
- ["Naomichi", "Matsumoto"],
- ["Takeshi", "Mizuguchi"]
+ ["Simon", "Frachet"],
+ ["Pauline", "Chazelas"],
+ ["Laurent", "Magy"],
+ ["Pascal", "Cintas"],
+ ["Danielle", "Brouqui\u00e8res"],
+ ["Pierre", "Girardie"],
+ ["Louise", "Espagno"],
+ ["Boris", "Melloni"],
+ ["Laurent", "Guilleminault"],
+ ["Anne-Sophie", "Lia"]
],
- "publisher": "Clinical epigenetics",
- "issn": "1868-7083",
- "date": "2021-11-13",
- "abstract": "GGC repeat expansions in NOTCH2NLC are associated with neuronal intranuclear inclusion disease. Very recently, asymptomatic carriers with NOTCH2NLC repeat expansions were reported. In these asymptomatic individuals, the CpG island in NOTCH2NLC is hypermethylated, suggesting that two factors repeat length and DNA methylation status should be considered to evaluate pathogenicity. Long-read sequencing can be used to simultaneously profile genomic and epigenomic alterations. We analyzed four sporadic cases with NOTCH2NLC repeat expansion and their phenotypically normal parents. The native genomic DNA that retains base modification was sequenced on a per-trio basis using both PacBio and Oxford Nanopore long-read sequencing technologies. A custom workflow was developed to evaluate DNA modifications. With these two technologies combined, long-range DNA methylation information was integrated with complete repeat DNA sequences to investigate the genetic origins of expanded GGC repeats in these sporadic cases.",
+ "publisher": "Neurology. Genetics",
+ "issn": "2376-7839",
+ "date": "2024-07-19",
+ "abstract": "Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome results from variations in",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34774111"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39507594"
},
{
- "id": "pmid:34392981",
+ "id": "pmid:39416949",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/34392981",
- "title": "Analysis of NOTCH2NLC GGC repeat expansion in Taiwanese patients with amyotrophic lateral sclerosis.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/39416949",
+ "title": "Case report: Neuroacanthocytosis associated with novel variants in the",
"type": "article-journal",
- "doi": "10.1016/j.neurobiolaging.2021.07.011",
+ "doi": "10.3389/fnins.2024.1409366",
"authors": [
- ["Kang-Yang", "Jih"],
- ["Ying-Tsen", "Chou"],
- ["Pei-Chien", "Tsai"],
- ["Yi-Chu", "Liao"],
- ["Yi-Chung", "Lee"]
+ ["Martin", "Paucar"],
+ ["Josephine", "Wincent"],
+ ["Charlotta", "Rubin"],
+ ["Kevin", "Peikert"],
+ ["Josefin", "Kyhle"],
+ ["Stellan", "Herteg\u00e5rd"],
+ ["Riita", "M\u00f6ller"],
+ ["Soheir", "Beshara"],
+ ["Per", "Svenningsson"]
],
- "publisher": "Neurobiology of aging",
- "issn": "1558-1497",
- "date": "2021-07-23",
- "abstract": "The GGC repeat expansion in the 5'-untranslated region of NOTCH2NLC was recently identified as the cause of neuronal intranuclear inclusion disease (NIID). To determine if the NIID repeat expansion contributes to amyotrophic lateral sclerosis (ALS), we screened 304 unrelated ALS patients and 637 healthy controls for the GGC repeat expansion in NOTCH2NLC using repeat-primed PCR and fragment analysis. None of the ALS patients carried the GGC repeat expansion. The sizes of the GGC repeats ranged from 7 to 36 in the ALS patients and 4 to 46 in the controls. The distribution of the GGC repeat sizes did not differ between the two groups. Our findings indicate that the NOTCH2NLC GGC repeat expansion is absent or extremely rare in Taiwanese patients with ALS.",
+ "publisher": "Frontiers in neuroscience",
+ "issn": "1662-4548",
+ "date": "2024-10-02",
+ "abstract": "The diseases historically known as neuroacanthocytosis (NA) conditions include",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34392981"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39416949"
},
{
- "id": "pmid:34306035",
+ "id": "pmid:39286915",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/34306035",
- "title": "GGC Repeat Expansion in the",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/39286915",
+ "title": "Electrophysiological features of the peripheral neuropathy in patients with pathologic biallelic RFC1 repeat expansions.",
"type": "article-journal",
- "doi": "10.3389/fgene.2021.694790",
+ "doi": "10.1002/mus.28257",
"authors": [
- ["Hui", "Wang"],
- ["Jiaxi", "Yu"],
- ["Meng", "Yu"],
- ["Jianwen", "Deng"],
- ["Wei", "Zhang"],
- ["He", "Lv"],
- ["Jing", "Liu"],
- ["Xin", "Shi"],
- ["Wei", "Liang"],
- ["Zhirong", "Jia"],
- ["Daojun", "Hong"],
- ["Lingchao", "Meng"],
- ["Zhaoxia", "Wang"],
- ["Yun", "Yuan"]
+ ["Claudia", "Calezis"],
+ ["Nathalie", "Bonello-Palot"],
+ ["Annie", "Verschueren"],
+ ["Jean-Philippe", "Azulay"],
+ ["Etienne", "Fortanier"],
+ ["Aude-Marie", "Grapperon"],
+ ["Ludivine", "Kouton"],
+ ["Julien", "Gallard"],
+ ["Emmanuelle", "Salort-Campana"],
+ ["Shahram", "Attarian"],
+ ["Emilien", "Delmont"]
],
- "publisher": "Frontiers in genetics",
- "issn": "1664-8021",
- "date": "2021-07-07",
- "abstract": "There is still a considerable proportion of patients with inherited peripheral neuropathy (IPN) whose pathogenic genes are unknown. This study was intended to investigate whether the GGC repeat expansion in the",
+ "publisher": "Muscle & nerve",
+ "issn": "1097-4598",
+ "date": "2024-09-17",
+ "abstract": "Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is caused by RFC1 expansions. Sensory neuronopathy, polyneuropathy, and involvement of motor, autonomic, and cranial nerves have all been described with RFC1 expansions. We aimed to describe the electrodiagnostic features of patients with RFC1 expansions through multimodal electrophysiological investigations.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34306035"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39286915"
},
{
- "id": "pmid:34243731",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/34243731",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:34243731']' timed out after 3 seconds"
+ "id": "pmid:39076534",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/39076534",
+ "title": "Cerebellar ataxia, neuropathy and vestibular areflexia syndrome: a neurogenic cough prototype.",
+ "type": "article-journal",
+ "doi": "10.1183/23120541.00024-2024",
+ "authors": [
+ ["Laurent", "Guilleminault"],
+ ["Stuart B", "Mazzone"],
+ ["Pauline", "Chazelas"],
+ ["Simon", "Frachet"],
+ ["Anne-Sophie", "Lia"],
+ ["Laurent", "Magy"]
+ ],
+ "publisher": "ERJ open research",
+ "issn": "2312-0541",
+ "date": "2024-07-29",
+ "abstract": "Chronic cough is a frequent disorder that is defined by cough of more than 8\u2005weeks duration. Despite extensive investigation, some patients exhibit no aetiology and others do not respond to specific treatments directed against apparent causes of cough. Such patients are identified as having unexplained or refractory chronic cough. Recently, a high proportion of patients with chronic cough in the context of cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) was highlighted. CANVAS is a rare neurological disorder with a biallelic variation in the replication factor C subunit 1 (",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39076534"
},
{
- "id": "pmid:33871559",
+ "id": "pmid:38978724",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/33871559",
- "title": "Questions on NOTCH2NLC Repeat Expansions in Parkinson Disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38978724",
+ "title": "Pathologic",
"type": "article-journal",
- "doi": "10.1001/jamaneurol.2021.0747",
+ "doi": "10.1093/braincomms/fcae163",
"authors": [
- ["Wai Yan", "Yau"],
- ["Henry", "Houlden"],
- ["Jana", "Vandrovcova"]
+ ["Sara", "Nagy"],
+ ["Aisling", "Carr"],
+ ["Magdalena", "Mroczek"],
+ ["Simon", "Rinaldi"],
+ ["Riccardo", "Curro"],
+ ["Natalia", "Dominik"],
+ ["Nicole", "Japzon"],
+ ["Francesca", "Magrinelli"],
+ ["Michael P", "Lunn"],
+ ["Hadi", "Manji"],
+ ["Mary M", "Reilly"],
+ ["Andrea", "Cortese"],
+ ["Henry", "Houlden"]
],
- "publisher": "JAMA neurology",
- "issn": "2168-6157",
- "date": "2021-06-01",
- "abstract": "",
+ "publisher": "Brain communications",
+ "issn": "2632-1297",
+ "date": "2024-06-03",
+ "abstract": "Biallelic expansions of the AAGGG repeat in the replication factor C subunit 1 (",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33871559"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38978724"
},
{
- "id": "pmid:33871549",
+ "id": "pmid:38916676",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/33871549",
- "title": "Questions on NOTCH2NLC Repeat Expansions in Parkinson Disease-Reply.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38916676",
+ "title": "Analysis and occurrence of biallelic pathogenic repeat expansions in RFC1 in a German cohort of patients with a main clinical phenotype of motor neuron disease.",
"type": "article-journal",
- "doi": "10.1001/jamaneurol.2021.0768",
+ "doi": "10.1007/s00415-024-12519-6",
"authors": [
- ["Dongrui", "Ma"],
- ["Yi Jayne", "Tan"],
- ["Eng-King", "Tan"]
+ ["Annalisa", "Schaub"],
+ ["Hannes", "Erdmann"],
+ ["Veronika", "Scholz"],
+ ["Manuela", "Timmer"],
+ ["Isabell", "Cordts"],
+ ["Rene", "G\u00fcnther"],
+ ["Peter", "Reilich"],
+ ["Angela", "Abicht"],
+ ["Florian", "Sch\u00f6berl"]
],
- "publisher": "JAMA neurology",
- "issn": "2168-6157",
- "date": "2021-06-01",
- "abstract": "",
+ "publisher": "Journal of neurology",
+ "issn": "1432-1459",
+ "date": "2024-06-25",
+ "abstract": "Biallelic pathogenic repeat expansions in RFC1 were recently identified as molecular origin of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) as well as of one of the most common causes of adult-onset ataxia. In the meantime, the phenotypic spectrum has expanded massively and now includes mimics of multiple system atrophy or parkinsonism. After identifying a patient with a clinical diagnosis of amyotrophic lateral sclerosis (ALS) as a carrier of biallelic pathogenic repeat expansions in RFC1, we studied a cohort of 106 additional patients with a clinical main phenotype of motor neuron disease (MND) to analyze whether such repeat expansions are more common in MND patients. Indeed, two additional MND patients (one also with ALS and one with primary lateral sclerosis/PLS) have been identified as carrier of biallelic pathogenic repeat expansions in RFC1 in the absence of another genetic alteration explaining the phenotype, suggesting motor neuron disease as another extreme phenotype of RFC1 spectrum disorder. Therefore, MND might belong to the expanding phenotypic spectrum of pathogenic RFC1 repeat expansions, particularly in those MND patients with additional features such as sensory and/or autonomic neuropathy, vestibular deficits, or cerebellar signs. By systematically analyzing the RFC1 repeat array using Oxford nanopore technology long-read sequencing, our study highlights the high intra- and interallelic heterogeneity of this locus and allows the identification of the novel repeat motif 'ACAAG'.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33871549"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38916676"
},
{
- "id": "pmid:33766934",
+ "id": "pmid:38789445",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/33766934",
- "title": "Genetic origin of sporadic cases and RNA toxicity in neuronal intranuclear inclusion disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38789445",
+ "title": "Profiling complex repeat expansions in RFC1 in Parkinson's disease.",
"type": "article-journal",
- "doi": "10.1136/jmedgenet-2020-107649",
+ "doi": "10.1038/s41531-024-00723-0",
"authors": [
- ["Jianwen", "Deng"],
- ["Binbin", "Zhou"],
- ["Jiaxi", "Yu"],
- ["Xiaochen", "Han"],
- ["Jianhui", "Fu"],
- ["Xiaobin", "Li"],
- ["Xufang", "Xie"],
- ["Min", "Zhu"],
- ["Yilei", "Zheng"],
- ["Xueyu", "Guo"],
- ["Pidong", "Li"],
- ["Qingqing", "Wang"],
- ["Jing", "Liu"],
- ["Wei", "Zhang"],
- ["Yun", "Yuan"],
- ["Sheng", "Yao"],
- ["Zhaoxia", "Wang"],
- ["Daojun", "Hong"]
+ ["Pilar", "Alvarez Jerez"],
+ ["Kensuke", "Daida"],
+ ["Abigail", "Miano-Burkhardt"],
+ ["Hirotaka", "Iwaki"],
+ ["Laksh", "Malik"],
+ ["Guillaume", "Cogan"],
+ ["Mary B", "Makarious"],
+ ["Roisin", "Sullivan"],
+ ["Jana", "Vandrovcova"],
+ ["Jinhui", "Ding"],
+ ["J Raphael", "Gibbs"],
+ ["Androo", "Markham"],
+ ["Mike A", "Nalls"],
+ ["Rupesh K", "Kesharwani"],
+ ["Fritz J", "Sedlazeck"],
+ ["Bradford", "Casey"],
+ ["John", "Hardy"],
+ ["Henry", "Houlden"],
+ ["Cornelis", "Blauwendraat"],
+ ["Andrew B", "Singleton"],
+ ["Kimberley J", "Billingsley"]
],
- "publisher": "Journal of medical genetics",
- "issn": "1468-6244",
- "date": "2021-03-25",
- "abstract": "GGC repeat expansion in",
+ "publisher": "NPJ Parkinson's disease",
+ "issn": "2373-8057",
+ "date": "2024-05-24",
+ "abstract": "A biallelic (AAGGG) expansion in the poly(A) tail of an AluSx3 transposable element within the gene RFC1 is a frequent cause of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS), and more recently, has been reported as a rare cause of Parkinson's disease (PD) in the Finnish population. Here, we investigate the prevalence of RFC1 (AAGGG) expansions in PD patients of non-Finnish European ancestry in 1609 individuals from the Parkinson's Progression Markers Initiative study. We identified four PD patients carrying the biallelic RFC1 (AAGGG) expansion and did not identify any carriers in controls.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33766934"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38789445"
},
{
- "id": "pmid:33388663",
+ "id": "pmid:38579416",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/33388663",
- "title": "Long-term MRI findings of adult-onset neuronal intranuclear inclusion disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38579416",
+ "title": "Bilateral vestibulopathy as the initial presentation of CANVAS.",
"type": "article-journal",
- "doi": "10.1016/j.clineuro.2020.106456",
+ "doi": "10.1016/j.jns.2024.122990",
"authors": [
- ["Kisaki", "Tachi"],
- ["Tadayuki", "Takata"],
- ["Kodai", "Kume"],
- ["Jun", "Sone"],
- ["Hideki", "Kobara"],
- ["Kazushi", "Deguchi"],
- ["Hideshi", "Kawakami"],
- ["Tsutomu", "Masaki"]
+ ["Carlos R", "Gordon"],
+ ["Roy", "Zaltzman"],
+ ["Dario", "Geisinger"],
+ ["Zohar", "Elyoseph"],
+ ["Yoav", "Gimmon"]
],
- "publisher": "Clinical neurology and neurosurgery",
- "issn": "1872-6968",
- "date": "2020-12-29",
- "abstract": "",
+ "publisher": "Journal of the neurological sciences",
+ "issn": "1878-5883",
+ "date": "2024-04-02",
+ "abstract": "Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a slowly progressing autosomal recessive ataxic disorder linked to an abnormal biallelic intronic (most commonly) AAGGG repeat expansion in the replication factor complex subunit 1 (RFC1). While the clinical diagnosis is relatively straightforward when the three components of the disorder are present, it becomes challenging when only one of the triad (cerebellar ataxia, neuropathy or vestibular areflexia) manifests. Isolated cases of Bilateral Vestibulopathy (BVP) or vestibular areflexia that later developed the other components of CANVAS have not been documented. We report four cases of patients with chronic imbalance and BVP that, after several years, developed cerebellar and neuropathic deficits with positive genetic testing for RFC1. Our report supports the concept that CANVAS should be considered in every patient with BVP of unknown etiology, even without the presence of the other triad components. This is especially important given that about 50% of cases in many BVP series are diagnosed as idiopathic, some of which may be undiagnosed CANVAS.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33388663"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38579416"
},
{
- "id": "pmid:33377220",
+ "id": "pmid:38311638",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/33377220",
- "title": "NOTCH2NLC Intermediate-Length Repeat Expansion and Parkinson's Disease in Patients of European Descent.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38311638",
+ "title": "The impact of folate pathway variants on the outcome of methotrexate therapy in rheumatoid arthritis patients.",
"type": "article-journal",
- "doi": "10.1002/ana.26003",
+ "doi": "10.1007/s10067-024-06892-w",
"authors": [
- ["Wai Yan", "Yau"],
- ["Roisin", "Sullivan"],
- ["Clarissa", "Rocca"],
- ["Elisa", "Cali"],
- ["Jana", "Vandrovcova"],
- ["Nicholas W", "Wood"],
- ["Henry", "Houlden"]
+ ["Azhar M", "Nomair"],
+ ["Abeer", "Abdelati"],
+ ["Fatma I", "Dwedar"],
+ ["Rehab", "Elnemr"],
+ ["Yasmine N", "Kamel"],
+ ["Hanan M", "Nomeir"]
],
- "publisher": "Annals of neurology",
- "issn": "1531-8249",
- "date": "2021-01-11",
- "abstract": "",
+ "publisher": "Clinical rheumatology",
+ "issn": "1434-9949",
+ "date": "2024-02-05",
+ "abstract": "There are currently no validated criteria that entirely explain or predict response to methotrexate (MTX) treatment in rheumatoid arthritis (RA). We tried to identify the connection between three variants (RFC1 G80A (rs1051266), TYMS 2R/3R (rs34743033), and ATIC C347G (rs2372536)) in the folate pathway of MTX metabolism and the response to MTX monotherapy in a cohort of RA cases.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33377220"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38311638"
},
{
- "id": "pmid:33377207",
+ "id": "pmid:38306376",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/33377207",
- "title": "Reply to \"NOTCH2NLC Intermediate-Length Repeat Expansions Are Associated with Parkinson Disease\".",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38306376",
+ "title": "Cerebellar Ataxia With Neuropathy and Vestibular Areflexia Syndrome Due to Replication Factor C Subunit 1 Gene Repeat Expansion.",
"type": "article-journal",
- "doi": "10.1002/ana.26005",
+ "doi": "10.1097/rlu.0000000000005047",
"authors": [
- ["Chang-He", "Shi"],
- ["Yu", "Fan"],
- ["Yu-Ming", "Xu"]
+ ["Mitsuteru", "Tsuchiya"],
+ ["Tomoyasu", "Bunai"],
+ ["Kazuki", "Watanabe"],
+ ["Hirotomo", "Saitsu"],
+ ["Satoshi", "Goshima"]
],
- "publisher": "Annals of neurology",
- "issn": "1531-8249",
- "date": "2021-01-11",
- "abstract": "",
+ "publisher": "Clinical nuclear medicine",
+ "issn": "1536-0229",
+ "date": "2024-01-15",
+ "abstract": "A 56-year-old man was born to consanguineous parents. He experienced slow-progressing sensory disturbances in the upper extremities. T1-weighted images showed cerebellar atrophy. 123I-IMP SPECT revealed reduced cerebral blood flow in the cerebellum. 123I-FP-CIT SPECT showed low uptake of dopamine transporter in the bilateral tail of the striatum. 123I-MIBG scintigraphy shows a decreased heart-to-mediastinum ratio. Flanking polymerase chain reaction suggested biallelic repeat expansion in intron 2 of RFC1, and subsequent repeat-primed polymerase chain reaction revealed ACAGG repeat expansion. Thus, he was diagnosed as cerebellar ataxia with neuropathy and vestibular areflexia syndrome.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33377207"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38306376"
},
{
- "id": "pmid:33146671",
+ "id": "pmid:38193360",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/33146671",
- "title": "Assessing the NOTCH2NLC GGC expansion in European patients with essential tremor.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38193360",
+ "title": "Role of the repeat expansion size in predicting age of onset and severity in RFC1 disease.",
"type": "article-journal",
- "doi": "10.1093/brain/awaa291",
+ "doi": "10.1093/brain/awad436",
"authors": [
- ["Calwing", "Liao"],
- ["Fulya", "Ak\u00e7imen"],
- ["Monica", "Diez-Fairen"],
- ["Gabrielle", "Houle"],
- ["Jay P", "Ross"],
- ["Zoe", "Schmilovich"],
- ["Dan", "Spiegelman"],
- ["Veikko", "Vuokila"],
- ["H\u00e9l\u00e8ne", "Catoire"],
- ["Inge A", "Meijer"],
- ["Pau", "Pastor"],
- ["Alex", "Rajput"],
- ["Patrick A", "Dion"],
- ["Guy A", "Rouleau"]
+ ["Riccardo", "Curr\u00f2"],
+ ["Natalia", "Dominik"],
+ ["Stefano", "Facchini"],
+ ["Elisa", "Vegezzi"],
+ ["Roisin", "Sullivan"],
+ ["Valentina", "Galassi Deforie"],
+ ["Gorka", "Fern\u00e1ndez-Eulate"],
+ ["Andreas", "Trasch\u00fctz"],
+ ["Salvatore", "Rossi"],
+ ["Matteo", "Garibaldi"],
+ ["Mariusz", "Kwarciany"],
+ ["Franco", "Taroni"],
+ ["Alfredo", "Brusco"],
+ ["Jean-Marc", "Good"],
+ ["Francesca", "Cavalcanti"],
+ ["Simon", "Hammans"],
+ ["Gianina", "Ravenscroft"],
+ ["Richard H", "Roxburgh"],
+ ["Ricardo", "Parolin Schnekenberg"],
+ ["Bianca", "Rugginini"],
+ ["Elena", "Abati"],
+ ["Arianna", "Manini"],
+ ["Ilaria", "Quartesan"],
+ ["Arianna", "Ghia"],
+ ["Adolfo", "L\u00f2pez de Muna\u00ecn"],
+ ["Fiore", "Manganelli"],
+ ["Marina", "Kennerson"],
+ ["Filippo Maria", "Santorelli"],
+ ["Jon", "Infante"],
+ ["Wilson", "Marques"],
+ ["Manu", "Jokela"],
+ ["Sin\u00e9ad M", "Murphy"],
+ ["Paola", "Mandich"],
+ ["Gian Maria", "Fabrizi"],
+ ["Chiara", "Briani"],
+ ["David", "Gosal"],
+ ["Davide", "Pareyson"],
+ ["Alberto", "Ferrari"],
+ ["Ferran", "Prados"],
+ ["Tarek", "Yousry"],
+ ["Vikram", "Khurana"],
+ ["Sheng-Han", "Kuo"],
+ ["James", "Miller"],
+ ["Claire", "Troakes"],
+ ["Zane", "Jaunmuktane"],
+ ["Paola", "Giunti"],
+ ["Annette", "Hartmann"],
+ ["Nazli", "Basak"],
+ ["Matthis", "Synofzik"],
+ ["Tanya", "Stojkovic"],
+ ["Marios", "Hadjivassiliou"],
+ ["Mary M", "Reilly"],
+ ["Henry", "Houlden"],
+ ["Andrea", "Cortese"]
],
"publisher": "Brain : a journal of neurology",
"issn": "1460-2156",
- "date": "2020-12-05",
- "abstract": "",
+ "date": "2024-05-03",
+ "abstract": "RFC1 disease, caused by biallelic repeat expansion in RFC1, is clinically heterogeneous in terms of age of onset, disease progression and phenotype. We investigated the role of the repeat size in influencing clinical variables in RFC1 disease. We also assessed the presence and role of meiotic and somatic instability of the repeat. In this study, we identified 553 patients carrying biallelic RFC1 expansions and measured the repeat expansion size in 392 cases. Pearson's coefficient was calculated to assess the correlation between the repeat size and age at disease onset. A Cox model with robust cluster standard errors was adopted to describe the effect of repeat size on age at disease onset, on age at onset of each individual symptoms, and on disease progression. A quasi-Poisson regression model was used to analyse the relationship between phenotype and repeat size. We performed multivariate linear regression to assess the association of the repeat size with the degree of cerebellar atrophy. Meiotic stability was assessed by Southern blotting on first-degree relatives of 27 probands. Finally, somatic instability was investigated by optical genome mapping on cerebellar and frontal cortex and unaffected peripheral tissue from four post-mortem cases. A larger repeat size of both smaller and larger allele was associated with an earlier age at neurological onset [smaller allele hazard ratio (HR) = 2.06, P < 0.001; larger allele HR = 1.53, P < 0.001] and with a higher hazard of developing disabling symptoms, such as dysarthria or dysphagia (smaller allele HR = 3.40, P < 0.001; larger allele HR = 1.71, P = 0.002) or loss of independent walking (smaller allele HR = 2.78, P < 0.001; larger allele HR = 1.60; P < 0.001) earlier in disease course. Patients with more complex phenotypes carried larger expansions [smaller allele: complex neuropathy rate ratio (RR) = 1.30, P = 0.003; cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) RR = 1.34, P < 0.001; larger allele: complex neuropathy RR = 1.33, P = 0.008; CANVAS RR = 1.31, P = 0.009]. Furthermore, larger repeat expansions in the smaller allele were associated with more pronounced cerebellar vermis atrophy (lobules I-V \u03b2 = -1.06, P < 0.001; lobules VI-VII \u03b2 = -0.34, P = 0.005). The repeat did not show significant instability during vertical transmission and across different tissues and brain regions. RFC1 repeat size, particularly of the smaller allele, is one of the determinants of variability in RFC1 disease and represents a key prognostic factor to predict disease onset, phenotype and severity. Assessing the repeat size is warranted as part of the diagnostic test for RFC1 expansion.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33146671"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38193360"
},
{
- "id": "pmid:33026126",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/33026126",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:33026126']' timed out after 3 seconds"
+ "id": "pmid:38145611",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38145611",
+ "title": "Unraveling the genetic landscape of undiagnosed cerebellar ataxia in Brazilian patients.",
+ "type": "article-journal",
+ "doi": "10.1016/j.parkreldis.2023.105961",
+ "authors": [
+ ["Luiz Eduardo", "Novis"],
+ ["Shahryar", "Alavi"],
+ ["David", "Pellerin"],
+ ["Marcus Vinicius", "Della Coleta"],
+ ["Salmo", "Raskin"],
+ ["Mariana", "Spitz"],
+ ["Andrea", "Cortese"],
+ ["Henry", "Houlden"],
+ ["Helio Afonso", "Teive"]
+ ],
+ "publisher": "Parkinsonism & related disorders",
+ "issn": "1873-5126",
+ "date": "2023-12-20",
+ "abstract": "Hereditary ataxias (HAs) encompass a diverse and genetically intricate group of rare neurodegenerative disorders, presenting diagnostic challenges. Whole-exome sequencing (WES) has significantly improved diagnostic success. This study aimed to elucidate genetic causes of cerebellar ataxia within a diverse Brazilian cohort.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38145611"
},
{
- "id": "pmid:33016348",
+ "id": "pmid:38062616",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/33016348",
- "title": "NOTCH2NLC Intermediate-Length Repeat Expansions Are Associated with Parkinson Disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38062616",
+ "title": "RNA Foci in Two bi-Allelic RFC1 Expansion Carriers.",
"type": "article-journal",
- "doi": "10.1002/ana.25925",
+ "doi": "10.1002/ana.26848",
"authors": [
- ["Chang-He", "Shi"],
- ["Yu", "Fan"],
- ["Jing", "Yang"],
- ["Yan-Peng", "Yuan"],
- ["Si", "Shen"],
- ["Fen", "Liu"],
- ["Cheng-Yuan", "Mao"],
- ["Han", "Liu"],
- ["Shuo", "Zhang"],
- ["Zheng-Wei", "Hu"],
- ["Li-Yuan", "Fan"],
- ["Meng-Jie", "Li"],
- ["Shi-Heng", "Fan"],
- ["Xiao-Jing", "Liu"],
- ["Yu-Ming", "Xu"]
+ ["Taishi", "Wada"],
+ ["Hiroshi", "Doi"],
+ ["Masaki", "Okubo"],
+ ["Mikiko", "Tada"],
+ ["Naohisa", "Ueda"],
+ ["Hidefumi", "Suzuki"],
+ ["Wakana", "Tominaga"],
+ ["Haruki", "Koike"],
+ ["Hiroyasu", "Komiya"],
+ ["Shun", "Kubota"],
+ ["Shunta", "Hashiguchi"],
+ ["Haruko", "Nakamura"],
+ ["Keita", "Takahashi"],
+ ["Misako", "Kunii"],
+ ["Kenichi", "Tanaka"],
+ ["Yosuke", "Miyaji"],
+ ["Yuichi", "Higashiyama"],
+ ["Eriko", "Koshimizu"],
+ ["Satoko", "Miyatake"],
+ ["Masahisa", "Katsuno"],
+ ["Satoshi", "Fujii"],
+ ["Hidehisa", "Takahashi"],
+ ["Naomichi", "Matsumoto"],
+ ["Hideyuki", "Takeuchi"],
+ ["Fumiaki", "Tanaka"]
],
"publisher": "Annals of neurology",
"issn": "1531-8249",
- "date": "2020-10-19",
- "abstract": "NOTCH2NLC GGC repeat expansions were recently identified in neuronal intranuclear inclusion disease (NIID); however, it remains unclear whether they occur in other neurodegenerative disorders. This study aimed to investigate the role of intermediate-length NOTCH2NLC GGC repeat expansions in Parkinson disease (PD). We screened for GGC repeat expansions in a cohort of 1,011 PD patients and identified 11 patients with intermediate-length repeat expansions ranging from 41 to 52 repeats, with no repeat expansions in 1,134 controls. Skin biopsy revealed phospho-alpha-synuclein deposition, confirming the PD diagnosis in 2 patients harboring intermediate-length repeat expansions instead of NIID or essential tremor. Fibroblasts from PD patients harboring intermediate-length repeat expansions revealed NOTCH2NLC upregulation and autophagic dysfunction. Our results suggest that intermediate-length repeat expansions in NOTCH2NLC are potentially associated with PD. ANN NEUROL 2021;89:182-187.",
+ "date": "2023-12-27",
+ "abstract": "Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is a late-onset, autosomal recessive neurodegenerative disorder caused by biallelic AAGGG/ACAGG repeat expansion (AAGGG-exp/ACAGG-exp) in RFC1. The recent identification of patients with CANVAS exhibiting compound heterozygosity for AAGGG-exp and truncating variants supports the loss-of-function of RFC1 in CANVAS patients. We investigated the pathological changes in 2 autopsied patients with CANVAS harboring biallelic ACAGG-exp and AAGGG-exp. RNA fluorescence in situ hybridization of the 2 patients revealed CCTGT- and CCCTT-containing RNA foci, respectively, in neuronal nuclei of tissues with neuronal loss. Our findings suggest that RNA toxicity may be involved in the pathogenesis of CANVAS. ANN NEUROL 2024;95:607-613.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33016348"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38062616"
},
{
- "id": "pmid:32817896",
+ "id": "pmid:38054570",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/32817896",
- "title": "A case of neuronal intranuclear inclusion disease with recurrent vomiting and without apparent DWI abnormality for the first seven years.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38054570",
+ "title": "Serum Neurofilament Light Chain in Replication Factor Complex Subunit 1 CANVAS and Disease Spectrum.",
"type": "article-journal",
- "doi": "10.1016/j.heliyon.2020.e04675",
+ "doi": "10.1002/mds.29680",
"authors": [
- ["Shun", "Okamura"],
- ["Makoto", "Takahashi"],
- ["Keisuke", "Abe"],
- ["Akira", "Inaba"],
- ["Jun", "Sone"],
- ["Satoshi", "Orimo"]
+ ["Ilaria", "Quartesan"],
+ ["Elisa", "Vegezzi"],
+ ["Riccardo", "Curr\u00f2"],
+ ["Amanda", "Heslegrave"],
+ ["Chiara", "Pisciotta"],
+ ["Pablo", "Iruzubieta"],
+ ["Alessandro", "Salvalaggio"],
+ ["Gorka", "Fern\u00e1ndez-Eulate"],
+ ["Natalia", "Dominik"],
+ ["Bianca", "Rugginini"],
+ ["Arianna", "Manini"],
+ ["Elena", "Abati"],
+ ["Stefano", "Facchini"],
+ ["Katarina", "Manso"],
+ ["Ines", "Albajar"],
+ ["Rhiannon", "Laban"],
+ ["Alexander M", "Rossor"],
+ ["Anna", "Pichiecchio"],
+ ["Giuseppe", "Cosentino"],
+ ["Paola", "Saveri"],
+ ["Ettore", "Salsano"],
+ ["Francesca", "Andreetta"],
+ ["Enza M", "Valente"],
+ ["Henrik", "Zetterberg"],
+ ["Paola", "Giunti"],
+ ["Tanya", "Stojkovic"],
+ ["Chiara", "Briani"],
+ ["Adolfo", "L\u00f3pez de Munain"],
+ ["Davide", "Pareyson"],
+ ["Mary M", "Reilly"],
+ ["Henry", "Houlden"],
+ ["Cristina", "Tassorelli"],
+ ["Andrea", "Cortese"]
],
- "publisher": "Heliyon",
- "issn": "2405-8440",
- "date": "2020-08-11",
- "abstract": "Neuronal intranuclear inclusion disease (NIID) is a rare, neurodegenerative disorder characterized by the presence of eosinophilic hyaline intranuclear inclusions, which are ubiquitin-positive and p62-positive, in neuronal and somatic cells; this can be observed on skin biopsy. Although patients with NIID present with a variety of symptoms that often make the diagnosis difficult, characteristic high-signal intensity of the corticomedullary junction on diffusion-weighted imaging (DWI) often provides a clue to the diagnosis of NIID. We present a case of NIID in a 57-year-old woman who only had recurrent vomiting for four years, which is uncommon as the presenting symptom; moreover, DWI showed no apparent abnormality until a slightly abnormal intensity lesion appeared at the right frontal corticomedullary junction seven years after the first episode of recurrent vomiting. Skin biopsies revealed multiple p62-positive nuclear inclusions, and genetic test showed GGC repeat expansion in",
+ "publisher": "Movement disorders : official journal of the Movement Disorder Society",
+ "issn": "1531-8257",
+ "date": "2023-12-06",
+ "abstract": "Biallelic intronic AAGGG repeat expansions in the replication factor complex subunit 1 (RFC1) gene were identified as the leading cause of cerebellar ataxia, neuropathy, vestibular areflexia syndrome. Patients exhibit significant clinical heterogeneity and variable disease course, but no potential biomarker has been identified to date.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32817896"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38054570"
},
{
- "id": "pmid:32777174",
+ "id": "pmid:37892228",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/32777174",
- "title": "Neuronal intranuclear inclusion disease is genetically heterogeneous.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/37892228",
+ "title": "Optical Genome Mapping Enables Detection and Accurate Sizing of",
"type": "article-journal",
- "doi": "10.1002/acn3.51151",
+ "doi": "10.3390/biom13101546",
"authors": [
- ["Zhongbo", "Chen"],
- ["Wai", "Yan Yau"],
- ["Zane", "Jaunmuktane"],
- ["Arianna", "Tucci"],
- ["Prasanth", "Sivakumar"],
- ["Sarah A", "Gagliano Taliun"],
- ["Chris", "Turner"],
+ ["Stefano", "Facchini"],
+ ["Natalia", "Dominik"],
+ ["Arianna", "Manini"],
["Stephanie", "Efthymiou"],
- ["Kristina", "Ib\u00e1\u00f1ez"],
- ["Roisin", "Sullivan"],
- ["Farah", "Bibi"],
- ["Alkyoni", "Athanasiou-Fragkouli"],
- ["Thomas", "Bourinaris"],
- ["David", "Zhang"],
- ["Tamas", "Revesz"],
- ["Tammaryn", "Lashley"],
- ["Michael", "DeTure"],
- ["Dennis W", "Dickson"],
- ["Keith A", "Josephs"],
- ["Ellen", "Gelpi"],
- ["Gabor G", "Kovacs"],
- ["Glenda", "Halliday"],
- ["Dominic B", "Rowe"],
- ["Ian", "Blair"],
- ["Pentti J", "Tienari"],
- ["Anu", "Suomalainen"],
- ["Nick C", "Fox"],
- ["Nicholas W", "Wood"],
- ["Andrew J", "Lees"],
- ["Matti J", "Haltia"],
- ["John", "Hardy"],
- ["Mina", "Ryten"],
- ["Jana", "Vandrovcova"],
- ["Henry", "Houlden"]
+ ["Riccardo", "Curr\u00f2"],
+ ["Bianca", "Rugginini"],
+ ["Elisa", "Vegezzi"],
+ ["Ilaria", "Quartesan"],
+ ["Benedetta", "Perrone"],
+ ["Shahedah Koya", "Kutty"],
+ ["Valentina", "Galassi Deforie"],
+ ["Ricardo P", "Schnekenberg"],
+ ["Elena", "Abati"],
+ ["Anna", "Pichiecchio"],
+ ["Enza Maria", "Valente"],
+ ["Cristina", "Tassorelli"],
+ ["Mary M", "Reilly"],
+ ["Henry", "Houlden"],
+ ["Enrico", "Bugiardini"],
+ ["Andrea", "Cortese"]
],
- "publisher": "Annals of clinical and translational neurology",
- "issn": "2328-9503",
- "date": "2020-08-10",
- "abstract": "Neuronal intranuclear inclusion disease (NIID) is a clinically heterogeneous neurodegenerative condition characterized by pathological intranuclear eosinophilic inclusions. A CGG repeat expansion in NOTCH2NLC was recently identified to be associated with NIID in patients of Japanese descent. We screened pathologically confirmed European NIID, cases of neurodegenerative disease with intranuclear inclusions and applied in silico-based screening using whole-genome sequencing data from 20\u00a0536 participants in the 100\u00a0000 Genomes Project. We identified a single European case harbouring the pathogenic repeat expansion with a distinct haplotype structure. Thus, we propose new diagnostic criteria as European NIID represents a distinct disease entity from East Asian cases.",
+ "publisher": "Biomolecules",
+ "issn": "2218-273X",
+ "date": "2023-10-19",
+ "abstract": "A recessive Short Tandem Repeat expansion in",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32777174"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37892228"
},
{
- "id": "pmid:32768149",
+ "id": "pmid:37853169",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/32768149",
- "title": "No genetic evidence for the involvement of GGC repeat expansions of the NOTCH2NLC gene in Chinese patients with multiple system atrophy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/37853169",
+ "title": "CANVAS-related RFC1 mutations in patients with immune-mediated neuropathy.",
"type": "article-journal",
- "doi": "10.1016/j.neurobiolaging.2020.07.008",
+ "doi": "10.1038/s41598-023-45011-8",
"authors": [
- ["Keqin", "Xu"],
- ["Linlin", "Wan"],
- ["Zhao", "Chen"],
- ["Chunrong", "Wang"],
- ["Huirong", "Peng"],
- ["Xuan", "Hou"],
- ["Yuting", "Shi"],
- ["Rong", "Qiu"],
- ["Beisha", "Tang"],
- ["Hong", "Jiang"]
+ ["Makito", "Hirano"],
+ ["Motoi", "Kuwahara"],
+ ["Yuko", "Yamagishi"],
+ ["Makoto", "Samukawa"],
+ ["Kanako", "Fujii"],
+ ["Shoko", "Yamashita"],
+ ["Masahiro", "Ando"],
+ ["Nobuyuki", "Oka"],
+ ["Mamoru", "Nagano"],
+ ["Taro", "Matsui"],
+ ["Toshihide", "Takeuchi"],
+ ["Kazumasa", "Saigoh"],
+ ["Susumu", "Kusunoki"],
+ ["Hiroshi", "Takashima"],
+ ["Yoshitaka", "Nagai"]
],
- "publisher": "Neurobiology of aging",
- "issn": "1558-1497",
- "date": "2020-07-15",
- "abstract": "Recent studies have identified an expanded GGC repeat in the 5' untranslated region of the NOTCH2NLC gene as a possible pathogenic genetic cause of neuronal intranuclear inclusion disease. Converging evidence verifying the presence of the same GGC repeat expansion in patients with Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases has also received increased attention. Inspired by some of the clinical similarities between neuronal intranuclear inclusion disease and multiple system atrophy (MSA), we used repeat-primed PCR to explore the occurrence of GGC repeats in 328 patients with MSA in mainland China. Our result failed to detect any GGC repeat expansion in these patients with MSA, indicating that the NOTCH2NLC gene may not be involved in the pathogenesis of MSA.",
+ "publisher": "Scientific reports",
+ "issn": "2045-2322",
+ "date": "2023-10-18",
+ "abstract": "Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) has recently been attributed to biallelic repeat expansions in RFC1. More recently, the disease entity has expanded to atypical phenotypes, including chronic neuropathy without cerebellar ataxia or vestibular areflexia. Very recently, RFC1 expansions were found in patients with Sj\u00f6gren syndrome who had neuropathy that did not respond to immunotherapy. In this study RFC1 was examined in 240 patients with acute or chronic neuropathies, including 105 with Guillain-Barr\u00e9 syndrome or Miller Fisher syndrome, 76 with chronic inflammatory demyelinating polyneuropathy, and 59 with other types of chronic neuropathy. Biallelic RFC1 mutations were found in three patients with immune-mediated neuropathies, including Guillain-Barr\u00e9 syndrome, idiopathic sensory ataxic neuropathy, or anti-myelin-associated glycoprotein (MAG) neuropathy, who responded to immunotherapies. In addition, a patient with chronic sensory autonomic neuropathy had biallelic mutations, and subclinical changes in Schwann cells on nerve biopsy. In summary,\u00a0we found CANVAS-related RFC1 mutations in patients with treatable immune-mediated neuropathy or demyelinating neuropathy.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32768149"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37853169"
},
{
- "id": "pmid:32495371",
+ "id": "pmid:37660923",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/32495371",
- "title": "NOTCH2NLC GGC Repeat Expansions Are Associated with Sporadic Essential Tremor: Variable Disease Expressivity on Long-Term Follow-up.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/37660923",
+ "title": "Pathogenic CANVAS-causing but not nonpathogenic RFC1 DNA/RNA repeat motifs form quadruplex or triplex structures.",
"type": "article-journal",
- "doi": "10.1002/ana.25803",
+ "doi": "10.1016/j.jbc.2023.105202",
"authors": [
- ["Adeline S L", "Ng"],
- ["Weng Khong", "Lim"],
- ["Zheyu", "Xu"],
- ["Helen L", "Ong"],
- ["Yi Jayne", "Tan"],
- ["Wei Ying", "Sim"],
- ["Ebonne Y L", "Ng"],
- ["Jing Xian", "Teo"],
- ["Jia Nee", "Foo"],
- ["Tchoyoson C C", "Lim"],
- ["Wai-Yung", "Yu"],
- ["Ling-Ling", "Chan"],
- ["Hwei-Yee", "Lee"],
- ["Zhiyong", "Chen"],
- ["Ee-Wei", "Lim"],
- ["Simon K S", "Ting"],
- ["Kumar M", "Prakash"],
- ["Louis C S", "Tan"],
- ["Zhao", "Yi"],
- ["Eng-King", "Tan"]
+ ["Mohammad Hossein", "Abdi"],
+ ["Bita", "Zamiri"],
+ ["Gholamreza", "Pazuki"],
+ ["Soroush", "Sardari"],
+ ["Christopher E", "Pearson"]
],
- "publisher": "Annals of neurology",
- "issn": "1531-8249",
- "date": "2020-07-16",
- "abstract": "We screened 662 subjects comprising 462 essential tremor (ET) subjects (285 sporadic, 125 with family history, and 52 probands from well-characterized ET pedigrees) and 200 controls and identified pathogenic NOTCH2NLC GGC repeat expansions in 4 sporadic ET patients. Two patients were followed up for >1 decade; one with 90 repeats remained an ET phenotype that did not evolve after 40\u2009years, whereas another patient with 107 repeats developed motor symptoms and cognitive impairment after 8 to 10\u2009years. Neuroimaging in this patient revealed severe leukoencephalopathy; diffusion-weighted imaging hyperintensity in the corticomedullary junction and skin biopsy revealed intranuclear inclusions suggestive of intranuclear inclusion body disease (NIID). No GGC repeats of >60\u2009units were detected in familial ET cases and controls, although 4 ET patients carried 47 to 53 \"intermediate\" repeats. NOTCH2NLC GGC repeat expansions can be associated with sporadic ET. Carriers presenting with a pure ET phenotype may or may not convert to NIID up to 4 decades after initial tremor onset. ANN NEUROL 2020;88:614-618.",
+ "publisher": "The Journal of biological chemistry",
+ "issn": "1083-351X",
+ "date": "2023-09-01",
+ "abstract": "Biallelic expansions of various tandem repeat sequence motifs are possible in RFC1 (replication factor C subunit 1), encoding the DNA replication/repair protein RFC1, yet only certain repeat motifs cause cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). CANVAS presents enigmatic puzzles: The pathogenic path for CANVAS neither is known nor is it understood why some, but not all expanded, motifs are pathogenic. The most common pathogenic repeat is (AAGGG)n\u2022(CCCTT)n, whereas (AAAAG)n\u2022(CTTTT)n is the most common nonpathogenic motif. While both intronic motifs can be expanded and transcribed, only r(AAGGG)n is retained in the mutant RFC1 transcript. We show that only the pathogenic forms unusual nucleic acid structures. Specifically, DNA and RNA of the pathogenic d(AAGGG)4 and r(AAGGG)4 form G-quadruplexes in potassium solution. Nonpathogenic repeats did not form G-quadruplexes. Triple-stranded structures are formed by the pathogenic motifs but not by the nonpathogenic motifs. G- and C-richness of the pathogenic strands favor formation of G\u2022G\u2022G\u2022G-tetrads and protonated C+-G Hoogsteen base pairings, involved in quadruplex and triplex structures, respectively, stabilized by increased hydrogen bonds and pi-stacking interactions relative to A-T Hoogsteen pairs that could form by the nonpathogenic motif. The ligand, TMPyP4, binds the pathogenic quadruplexes. Formation of quadruplexes and triplexes by pathogenic repeats supports toxic-DNA and toxic-RNA modes of pathogenesis at the RFC1 gene and the RFC1 transcript. Our findings with short repeats provide insights into the disease specificity of pathogenic repeat motif sequences and reveal nucleic acid structural features that may be pathogenically involved and targeted therapeutically.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32495371"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37660923"
},
{
- "id": "pmid:32449905",
+ "id": "pmid:37546920",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/32449905",
- "title": "Essential tremor as the early symptom of NOTCH2NLC gene-related repeat expansion disorder.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/37546920",
+ "title": "Pathogenic CANVAS (AAGGG)",
"type": "article-journal",
- "doi": "10.1093/brain/awaa142",
+ "doi": "10.1101/2023.07.25.550509",
"authors": [
- ["Hao", "Chen"],
- ["Likui", "Lu"],
- ["Bin", "Wang"],
- ["Xiaodong", "Hua"],
- ["Bo", "Wan"],
- ["Miao", "Sun"],
- ["Xingshun", "Xu"]
+ ["Julia A", "Hisey"],
+ ["Elina A", "Radchenko"],
+ ["Silvia", "Ceschi"],
+ ["Anastasia", "Rastokina"],
+ ["Nicholas H", "Mandel"],
+ ["Ryan J", "McGinty"],
+ ["Gabriel", "Matos-Rodrigues"],
+ ["Alfredo", "Hernandez"],
+ ["Andr\u00e9", "Nussenzweig"],
+ ["Sergei M", "Mirkin"]
],
- "publisher": "Brain : a journal of neurology",
- "issn": "1460-2156",
- "date": "2020-07-01",
- "abstract": "",
+ "publisher": "bioRxiv : the preprint server for biology",
+ "issn": "2692-8205",
+ "date": "2023-07-26",
+ "abstract": "CANVAS is a recently characterized repeat expansion disease, most commonly caused by homozygous expansions of an intronic (A",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32449905"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37546920"
},
{
- "id": "pmid:32268889",
+ "id": "pmid:37476326",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/32268889",
- "title": "Multiple reversible encephalitic attacks: a rare manifestation of neuronal intranuclear inclusion disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/37476326",
+ "title": "Lower Facial Dystonia: An Unexpected Presentation Associated with Pathogenic",
"type": "article-journal",
- "doi": "10.1186/s12883-020-01712-5",
+ "doi": "10.1002/mdc3.13730",
"authors": [
- ["Mingming", "Li"],
- ["Kai", "Li"],
- ["Xin", "Li"],
- ["Yun", "Tian"],
- ["Lu", "Shen"],
- ["Guode", "Wu"],
- ["Zaiqiang", "Zhang"],
- ["Weian", "Chen"]
+ ["Joana", "Fonte"],
+ ["C\u00e9lia", "Machado"],
+ ["Jorge", "Oliveira"],
+ ["Marina", "Magalh\u00e3es"]
],
- "publisher": "BMC neurology",
- "issn": "1471-2377",
- "date": "2020-04-08",
- "abstract": "Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative condition characterized by the loss of neurons and the presence of eosinophilic nuclear inclusions in the central and peripheral nervous system, skin and visceral organs. In this paper, we present a case of NIID with recurrent encephalitic attacks that remained stable and nonprogressive for seven years; no such case has previously been reported.",
+ "publisher": "Movement disorders clinical practice",
+ "issn": "2330-1619",
+ "date": "2023-04-06",
+ "abstract": "",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32268889"
-},
-{
- "id": "pmid:31886491",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/31886491",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:31886491']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37476326"
},
{
- "id": "pmid:31819945",
+ "id": "pmid:37460231",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/31819945",
- "title": "Expansion of GGC repeat in the human-specific NOTCH2NLC gene is associated with essential tremor.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/37460231",
+ "title": "Frequency and Phenotype of",
"type": "article-journal",
- "doi": "10.1093/brain/awz372",
+ "doi": "10.1212/wnl.0000000000207553",
"authors": [
- ["Qi-Ying", "Sun"],
- ["Qian", "Xu"],
- ["Yun", "Tian"],
- ["Zheng-Mao", "Hu"],
- ["Li-Xia", "Qin"],
- ["Jin-Xia", "Yang"],
- ["Wen", "Huang"],
- ["Jin", "Xue"],
- ["Jin-Chen", "Li"],
- ["Sheng", "Zeng"],
- ["Ying", "Wang"],
- ["Hao-Xuan", "Min"],
- ["Xiao-Yu", "Chen"],
- ["Jun-Pu", "Wang"],
- ["Bin", "Xie"],
- ["Fan", "Liang"],
- ["Hai-Nan", "Zhang"],
- ["Chun-Yu", "Wang"],
- ["Li-Fang", "Lei"],
- ["Xin-Xiang", "Yan"],
- ["Hong-Wei", "Xu"],
- ["Ran-Hui", "Duan"],
- ["Kun", "Xia"],
- ["Jing-Yu", "Liu"],
- ["Hong", "Jiang"],
- ["Lu", "Shen"],
- ["Ji-Feng", "Guo"],
- ["Bei-Sha", "Tang"]
+ ["Andreas", "Trasch\u00fctz"],
+ ["Felix", "Heindl"],
+ ["Muhammad", "Bilal"],
+ ["Annette M", "Hartmann"],
+ ["Claudia", "Dufke"],
+ ["Olaf", "Riess"],
+ ["Andreas", "Zwergal"],
+ ["Dan", "Rujescu"],
+ ["Tobias", "Haack"],
+ ["Matthis", "Synofzik"],
+ ["Michael", "Strupp"]
],
- "publisher": "Brain : a journal of neurology",
- "issn": "1460-2156",
- "date": "2020-01-01",
- "abstract": "Essential tremor is one of the most common movement disorders. Despite its high prevalence and heritability, the genetic aetiology of essential tremor remains elusive. Up to now, only a few genes/loci have been identified, but these genes have not been replicated in other essential tremor families or cohorts. Here we report a genetic study in a cohort of 197 Chinese pedigrees clinically diagnosed with essential tremor. Using a comprehensive strategy combining linkage analysis, whole-exome sequencing, long-read whole-genome sequencing, repeat-primed polymerase chain reaction and GC-rich polymerase chain reaction, we identified an abnormal GGC repeat expansion in the 5' region of the NOTCH2NLC gene that co-segregated with disease in 11 essential tremor families (5.58%) from our cohort. Clinically, probands that had an abnormal GGC repeat expansion were found to have more severe tremor phenotypes, lower activities of daily living ability. Obvious genetic anticipation was also detected in these 11 essential tremor-positive families. These results indicate that abnormal GGC repeat expansion in the 5' region of NOTCH2NLC gene is associated with essential tremor, and provide strong evidence that essential tremor is a family of diseases with high clinical and genetic heterogeneities.",
+ "publisher": "Neurology",
+ "issn": "1526-632X",
+ "date": "2023-07-17",
+ "abstract": "Bilateral vestibulopathy (BVP) is a chronic debilitating neurologic disorder with no monogenic cause established so far despite familiar presentations. We hypothesized that replication factor complex subunit 1 (RFC1) repeat expansions might present a recurrent monogenic cause of BVP.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31819945"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37460231"
},
{
- "id": "pmid:31433517",
+ "id": "pmid:36805468",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/31433517",
- "title": "GGC Repeat Expansion of NOTCH2NLC in Adult Patients with Leukoencephalopathy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/36805468",
+ "title": "Generation and heterozygous repair of human iPSC lines from three individuals with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) carrying biallelic AAGGG expansions in RFC1.",
"type": "article-journal",
- "doi": "10.1002/ana.25586",
+ "doi": "10.1016/j.scr.2023.103047",
"authors": [
- ["Masaki", "Okubo"],
- ["Hiroshi", "Doi"],
- ["Ryoko", "Fukai"],
- ["Atsushi", "Fujita"],
- ["Satomi", "Mitsuhashi"],
- ["Shunta", "Hashiguchi"],
- ["Hitaru", "Kishida"],
- ["Naohisa", "Ueda"],
- ["Keisuke", "Morihara"],
- ["Akihiro", "Ogasawara"],
- ["Yuko", "Kawamoto"],
- ["Tatsuya", "Takahashi"],
- ["Keita", "Takahashi"],
- ["Haruko", "Nakamura"],
- ["Misako", "Kunii"],
- ["Mikiko", "Tada"],
- ["Atsuko", "Katsumoto"],
- ["Hiromi", "Fukuda"],
- ["Takeshi", "Mizuguchi"],
- ["Satoko", "Miyatake"],
- ["Noriko", "Miyake"],
- ["Junichiro", "Suzuki"],
- ["Yasuhiro", "Ito"],
- ["Jun", "Sone"],
- ["Gen", "Sobue"],
- ["Hideyuki", "Takeuchi"],
- ["Naomichi", "Matsumoto"],
- ["Fumiaki", "Tanaka"]
+ ["Kayli C", "Davies"],
+ ["Kiymet", "Bozaoglu"],
+ ["Paul J", "Lockhart"]
],
- "publisher": "Annals of neurology",
- "issn": "1531-8249",
- "date": "2019-10-22",
- "abstract": "Leukoencephalopathies comprise a broad spectrum of disorders, but the genetic background of adult leukoencephalopathies has rarely been assessed. In this study, we analyzed 101 Japanese patients with genetically unresolved adult leukoencephalopathy using whole-exome sequencing and repeat-primed polymerase chain reaction for detecting GGC expansion in NOTCH2NLC. NOTCH2NLC was recently identified as the cause of neuronal intranuclear inclusion disease. We found 12 patients with GGC expansion in NOTCH2NLC as the most frequent cause of adult leukoencephalopathy followed by NOTCH3 variants in our cohort. Furthermore, we found 1 case with de novo GGC expansion, which might explain the underlying pathogenesis of sporadic cases. ANN NEUROL 2019;86:962-968.",
+ "publisher": "Stem cell research",
+ "issn": "1876-7753",
+ "date": "2023-02-14",
+ "abstract": "Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is a progressive neurodegenerative disorder predominantly caused by biallelic AAGGG expansions in the second intron of the RFC1 gene. Here, we used a simultaneous reprogramming and CRISPR-Cas9 genome editing approach to generate three patient iPSC lines with homozygous AAGGG expansions along with three heterozygous gene corrected iPSC lines. The iPSC lines expressed pluripotency markers, had a normal karyotype, and were able to differentiate into all three embryonic germ layers. These mutant and corrected iPSC lines will be a valuable tool for studying the molecular mechanisms underlying CANVAS.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31433517"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36805468"
},
{
- "id": "pmid:40594369",
+ "id": "pmid:36753892",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/40594369",
- "title": "Feasibility of long-read sequencing to identify molecular alterations in an Indonesian cohort of locally advanced to advanced nasopharyngeal cancer.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/36753892",
+ "title": "RFC1 repeat expansions and cerebellar ataxia, neuropathy and vestibular areflexia syndrome: Experience and perspectives from a neuromuscular disorders unit.",
"type": "article-journal",
- "doi": "10.1038/s41598-025-06096-5",
+ "doi": "10.1016/j.jns.2023.120565",
"authors": [
- ["", "Handoko"],
- ["Marlinda", "Adham"],
- ["Lisnawati", "Rachmadi"],
- ["Demak Lumban", "Tobing"],
- ["", "Asmarinah"],
- ["", "Fadilah"],
- ["Wei", "Dai"],
- ["Anne Wing Mui", "Lee"],
- ["Soehartati A", "Gondhowiardjo"]
+ ["Daniel", "S\u00e1nchez-Tejerina"],
+ ["Paula Fernandez", "Alvarez"],
+ ["Elena", "La\u00ednez"],
+ ["Victoria Gonzalez", "Martinez"],
+ ["Daniela Isabel", "Santa-Cruz"],
+ ["Lena", "Verdaguer"],
+ ["Margarida", "Gratac\u00f2s"],
+ ["Jose Luis", "Seoane"],
+ ["N\u00faria", "Raguer"],
+ ["Jorge", "Hern\u00e1ndez-Vara"],
+ ["Arnau", "Llaurad\u00f3"],
+ ["Javier", "Sotoca"],
+ ["Maria", "Salvado"],
+ ["Elena Garcia", "Arumi"],
+ ["Eduardo F", "Tizzano"],
+ ["Ra\u00fal", "Juntas"]
],
- "publisher": "Scientific reports",
- "issn": "2045-2322",
- "date": "2025-07-01",
- "abstract": "Nasopharyngeal carcinoma (NPC) is prevalent in Southeast Asia, particularly in Indonesia. Despite advances in treatment, patients with advanced NPC face poor outcomes. Examining the NPC mutational landscape is crucial for understanding its biology and enable potential new therapeutic strategy. To characterize the landscape of single nucleotide variants (SNVs), structural variants (SVs), copy number variations (CNVs), and short tandem repeats (STRs) in locally advanced to advanced NPC within an Indonesian cohort using long-read sequencing. Six fresh-frozen nasopharyngeal biopsy samples were collected from the NPC biobank. DNA was extracted and sequenced using Oxford Nanopore's Promethion 2 Solo long-read sequencer. Structural and small variants were identified and annotated. The SNVs, SVs, and CNVs were categorized based on predicted effects, and key findings were validated using external RNA-seq data. Copy number loss genes were checked against the Tumour Suppressor Gene database (TSGene v2.0). Genetic findings were correlated with patient clinical histories. Approximately 4.4 to 5.1\u00a0million SNVs were identified per sample, with 0.023% categorized as high consequence. Notable tumour suppressor genes, such as LIMD1 and CNDP2, were frequently mutated. Around 30,000 to 41,599 SVs were detected per sample. High-consequence tumour suppressor gene SVs were identified in EPHA3, CASP8, DMBT1, ZFHX3, and IRF5 gene. Common copy number tumour suppressor gene loss observed in RNH1, H19, CDKN1C, and others, suggesting their role in NPC carcinogenesis. Copy number gains were found in potential oncogenes such as Y RNA, LTO1, and FADD. Pathogenic short tandem repeats (STRs) in PABPN1 and RFC1 were identified in three samples, presenting a novel association with NPC. NPC sample which exhibited significant genomic instability had the shortest survival, potentially linked to multiple defective DNA repair genes. This study utilized long-read sequencing to identify a complex spectrum of genetic alterations, including numerous SVs and potentially pathogenic STRs, in Indonesian NPC. Extensive DNA repair gene defects, primarily complex SVs detectable by long reads, were observed and highly possibly associated with poor survival. These findings underscore the potential of long-read sequencing for uncovering clinically relevant mutations in NPC.",
+ "publisher": "Journal of the neurological sciences",
+ "issn": "1878-5883",
+ "date": "2023-01-28",
+ "abstract": "Pathogenic expansions in RFC1 have been described as a cause of a spectrum of disorders including late-onset ataxia, chronic cough, and cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). Sensory neuronopathy/neuropathy appears to be a major symptom of RFC1-disorder, and RFC1 expansions are common in patients with sensory chronic idiopathic axonal neuropathy or sensory ganglionopathy. We aimed to investigate RFC1 expansions in patients with suspected RFC1-related disease followed-up in a Neuromuscular Diseases Unit, with a particular interest in the involvement of the peripheral nervous system.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40594369"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36753892"
},
{
- "id": "pmid:40552959",
+ "id": "pmid:36705320",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/40552959",
- "title": "Polyalanine Expansion in PABPN1 Alters the Structure and Dynamics of Its Nuclear Aggregates in Differentiated Muscle Cells.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/36705320",
+ "title": "Association of biallelic RFC1 expansion with early-onset Parkinson's disease.",
"type": "article-journal",
- "doi": "10.1096/fj.202501097r",
+ "doi": "10.1111/ene.15717",
"authors": [
- ["Sander D", "Mallon"],
- ["Erik", "Bos"],
- ["Vahid", "Sheikhhassani"],
- ["Milad", "Shademan"],
- ["Lenard M", "Voortman"],
- ["Alireza", "Mashaghi"],
- ["Thomas H", "Sharp"],
- ["Vered", "Raz"]
+ ["Pauli", "Ylikotila"],
+ ["Jussi", "Sipil\u00e4"],
+ ["Tiina", "Alapirtti"],
+ ["Riitta", "Ahmasalo"],
+ ["Eriko", "Koshimizu"],
+ ["Satoko", "Miyatake"],
+ ["Anri", "Hurme-Niiranen"],
+ ["Ari", "Siitonen"],
+ ["Hiroshi", "Doi"],
+ ["Fumiaki", "Tanaka"],
+ ["Naomichi", "Matsumoto"],
+ ["Kari", "Majamaa"],
+ ["Laura", "Kyt\u00f6vuori"]
],
- "publisher": "FASEB journal : official publication of the Federation of American Societies for Experimental Biology",
- "issn": "1530-6860",
- "date": "2025-06-30",
- "abstract": "Intracellular protein aggregation is a hallmark of aging and contributes to pathology in some age-associated diseases. In hereditary adult-onset neuromuscular diseases (NMDs), protein aggregates play a key role in disease onset and progression. The wild-type Poly(A) binding protein nuclear 1 (PABPN1) forms benign nuclear aggregates, whereas a short trinucleotide expansion leads to the formation of pathogenic aggregates, a hallmark of Oculopharyngeal Muscular Dystrophy (OPMD). In OPMD, the mutant PABPN1 causes skeletal muscle weakness. So far, the structural differences between benign and pathogenic protein aggregates and their effects on muscle cell biology remain poorly understood. We employed an array of advanced imaging modalities to explore the morphological differences between nuclear aggregates formed by non-pathogenic and pathogenic PABPN1 variants. Through analyses spanning micro- to nanoscale, we identified distinct structural features of aggregates formed by wild-type and expanded PABPN1. We demonstrate that these differences were more pronounced in differentiated muscle cells compared to proliferating cells. We further linked the structural features of PABPN1 aggregates to muscle cell biology, namely alterations in mitochondrial function and proteasomal activity. Our findings provide new insights into the structural distinctions between pathogenic and non-pathogenic aggregates and their implications for cellular dysfunction in NMDs.",
+ "publisher": "European journal of neurology",
+ "issn": "1468-1331",
+ "date": "2023-02-12",
+ "abstract": "The biallelic repeat expansion (AAGGG)",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40552959"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36705320"
},
{
- "id": "pmid:39113268",
+ "id": "pmid:36289003",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/39113268",
- "title": "Different outcomes of endurance and resistance exercise in skeletal muscles of Oculopharyngeal muscular dystrophy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/36289003",
+ "title": "Truncating Variants in",
"type": "article-journal",
- "doi": "10.1002/jcsm.13546",
+ "doi": "10.1212/wnl.0000000000201486",
"authors": [
- ["Alexis", "Boulinguiez"],
- ["Jamila", "Dhiab"],
- ["Barbara", "Crisol"],
- ["Laura", "Muraine"],
- ["Ludovic", "Gaut"],
- ["Corentin", "Rouxel"],
- ["Justine", "Flaire"],
- ["Hadidja-Rose", "Mouigni"],
- ["M\u00e9gane", "Lemaitre"],
- ["Benoit", "Giroux"],
- ["Lucie", "Audoux"],
- ["Benjamin", "SaintPierre"],
- ["Arnaud", "Ferry"],
- ["Vincent", "Mouly"],
- ["Gillian", "Butler-Browne"],
- ["Elisa", "Negroni"],
- ["Alberto", "Malerba"],
- ["Capucine", "Trollet"]
+ ["Riccardo", "Ronco"],
+ ["Cecilia", "Perini"],
+ ["Riccardo", "Curr\u00f2"],
+ ["Natalia", "Dominik"],
+ ["Stefano", "Facchini"],
+ ["Alice", "Gennari"],
+ ["Roberto", "Simone"],
+ ["Skye", "Stuart"],
+ ["Sara", "Nagy"],
+ ["Elisa", "Vegezzi"],
+ ["Ilaria", "Quartesan"],
+ ["Amar", "El-Saddig"],
+ ["Timothy", "Lavin"],
+ ["Arianna", "Tucci"],
+ ["Agnieszka", "Szymura"],
+ ["Luiz Eduardo", "Novis De Farias"],
+ ["Alexander", "Gary"],
+ ["Megan", "Delfeld"],
+ ["Priscilla", "Kandikatla"],
+ ["Nifang", "Niu"],
+ ["Sanjukta", "Tawde"],
+ ["Joseph", "Shaw"],
+ ["James", "Polke"],
+ ["Mary M", "Reilly"],
+ ["Nick W", "Wood"],
+ ["Emmanuele", "Crespan"],
+ ["Christopher", "Gomez"],
+ ["Jin Yun Helen", "Chen"],
+ ["Jeremy Dan", "Schmahmann"],
+ ["David", "Gosal"],
+ ["Henry", "Houlden"],
+ ["Soma", "Das"],
+ ["Andrea", "Cortese"]
],
- "publisher": "Journal of cachexia, sarcopenia and muscle",
- "issn": "2190-6009",
- "date": "2024-08-07",
- "abstract": "Exercise is widely considered to have beneficial impact on skeletal muscle aging. In addition, there are also several studies demonstrating a positive effect of exercise on muscular dystrophies. Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant inherited neuromuscular disorder caused by mutations in the PAPBN1 gene. These mutations consist in short (1-8) and meiotically stable GCN trinucleotide repeat expansions in its coding region responsible for the formation of PAPBN1 intranuclear aggregates. This study aims to characterize the effects of two types of chronic exercise, resistance and endurance, on the OPMD skeletal muscle phenotype using a relevant murine model of OPMD.",
+ "publisher": "Neurology",
+ "issn": "1526-632X",
+ "date": "2022-10-26",
+ "abstract": "Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is an autosomal recessive neurodegenerative disease characterized by adult-onset and slowly progressive sensory neuropathy, cerebellar dysfunction, and vestibular impairment. In most cases, the disease is caused by biallelic (AAGGG)",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39113268"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36289003"
},
{
- "id": "pmid:36790141",
+ "id": "pmid:36250766",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/36790141",
- "title": "Frequency and type of cancers in myotonic dystrophy: A retrospective cross-sectional study.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/36250766",
+ "title": "New Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome cases are caused by the presence of a nonsense variant in compound heterozygosity with the pathogenic repeat expansion in the RFC1 gene.",
"type": "article-journal",
- "doi": "10.1002/mus.27801",
+ "doi": "10.1111/cge.14249",
"authors": [
- ["Eleonora S", "D'Ambrosio"],
- ["Kathy", "Chuang"],
- ["William S", "David"],
- ["Anthony A", "Amato"],
- ["Paloma", "Gonzalez-Perez"]
+ ["Ana", "Arteche-L\u00f3pez"],
+ ["Almudena", "Avila-Fernandez"],
+ ["Alejandra", "Damian"],
+ ["Emma", "Soengas-Gonda"],
+ ["Rub\u00e9n P\u00e9rez", "de la Fuente"],
+ ["Patricia Ramos", "G\u00f3mez"],
+ ["Jes\u00fas Gallego", "Merlo"],
+ ["Laura Horcajada", "Burgos"],
+ ["Carlos Cemill\u00e1n", "Fern\u00e1ndez"],
+ ["Jose Miguel Lezana", "Rosales"],
+ ["Juan Francisco Gonz\u00e1lez", "Mart\u00ednez"],
+ ["Juan Francisco", "Quesada-Espinosa"],
+ ["Marta", "Corton"],
+ ["Maria Paz", "Guerrero-Molina"]
],
- "publisher": "Muscle & nerve",
- "issn": "1097-4598",
- "date": "2023-03-27",
- "abstract": "Myotonic dystrophies (DMs) are autosomal dominant diseases in which expression of a mutant expanded repeat mRNA leads to abnormal splicing of downstream effector genes thought to be responsible for their multisystem involvement. Cancer risk and cancer-related deaths are increased in DM patients relative to the general population. We aimed at determining the frequency and type of cancers in both DM1 and DM2 vs a non-DM muscular dystrophy cohort.",
+ "publisher": "Clinical genetics",
+ "issn": "1399-0004",
+ "date": "2022-11-03",
+ "abstract": "The biallelic pathogenic repeat (AAGGG)",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36790141"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36250766"
},
{
- "id": "pmid:35859342",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/35859342",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:35859342']' timed out after 3 seconds"
+ "id": "pmid:36177974",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/36177974",
+ "title": "Severe distinct dysautonomia in RFC1-related disease associated with Parkinsonism.",
+ "type": "article-journal",
+ "doi": "10.1111/jns.12515",
+ "authors": [
+ ["Christopher J", "Record"],
+ ["Rana Alnasser", "Alsukhni"],
+ ["Riccardo", "Curro"],
+ ["Diego", "Kaski"],
+ ["John S", "Rubin"],
+ ["Huw R", "Morris"],
+ ["Andrea", "Cortese"],
+ ["Valeria", "Iodice"],
+ ["Mary M", "Reilly"]
+ ],
+ "publisher": "Journal of the peripheral nervous system : JPNS",
+ "issn": "1529-8027",
+ "date": "2022-10-07",
+ "abstract": "Biallelic repeat expansions in replication factor C subunit 1 (RFC1) have recently been found to cause cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS). Additional features that have been described include Parkinsonism and a multiple system atrophy (MSA)-like syndrome. CANVAS can include features of dysautonomia, but they are much milder than typically seen in MSA. We report a detailed autonomic phenotype of multisystem RFC1-related disease presenting initially as CANVAS. Our patient presented aged 61 with a sensory ataxic neuropathy who rapidly developed widespread autonomic failure and Parkinsonism. The autonomic profile was of a mixed pre- and post-ganglionic syndrome with progressive involvement of sympathetic and parasympathetic cardiovascular and sudomotor function. The Parkinsonism did not respond to levodopa. We present a patient with CANVAS and biallelic RFC1 expansions who developed Parkinsonism with severe autonomic involvement similar to that seen in classical MSA. The link between MSA and CANVAS remains uncertain.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36177974"
},
{
- "id": "pmid:34225694",
+ "id": "pmid:36088850",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/34225694",
- "title": "A Japanese case of oculopharyngeal muscular dystrophy (OPMD) with PABPN1 c.35G\u2009>\u2009C; p.Gly12Ala point mutation.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/36088850",
+ "title": "Cognitive impairment is not uncommon in patients with biallelic RFC1 AAGGG repeat expansion, but the expansion is rare in patients with cognitive disease.",
"type": "article-journal",
- "doi": "10.1186/s12883-021-02300-x",
+ "doi": "10.1016/j.parkreldis.2022.08.034",
"authors": [
- ["Yo-Suke", "Nishii"],
- ["Yu-Ichi", "Noto"],
- ["Rei", "Yasuda"],
- ["Takamasa", "Kitaoji"],
- ["Shinji", "Ashida"],
- ["Eijirou", "Tanaka"],
- ["Narihiro", "Minami"],
- ["Ichizo", "Nishino"],
- ["Toshiki", "Mizuno"]
+ ["Anita", "Korpioja"],
+ ["Johanna", "Kr\u00fcger"],
+ ["Anri", "Hurme-Niiranen"],
+ ["Eino", "Solje"],
+ ["Kasper", "Katisko"],
+ ["Joonas", "Lipponen"],
+ ["Maria", "Lehtilahti"],
+ ["Anne M", "Remes"],
+ ["Kari", "Majamaa"],
+ ["Laura", "Kyt\u00f6vuori"]
],
- "publisher": "BMC neurology",
- "issn": "1471-2377",
- "date": "2021-07-05",
- "abstract": "Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscular dystrophy characterised by slowly progressive ptosis, dysphagia, and proximal limb muscle weakness. A common cause of OPMD is the short expansion of a GCG or GCA trinucleotide repeat in PABPN1 gene.",
+ "publisher": "Parkinsonism & related disorders",
+ "issn": "1873-5126",
+ "date": "2022-09-06",
+ "abstract": "The biallelic repeat expansion (AAGGG)",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34225694"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36088850"
},
{
- "id": "pmid:27980005",
+ "id": "pmid:35633373",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/27980005",
- "title": "Characterization of",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/35633373",
+ "title": "Screening for RFC-1 pathological expansion in late-onset ataxias: a contribution to the differential diagnosis.",
"type": "article-journal",
- "doi": "10.1136/jim-2016-000184",
+ "doi": "10.1007/s00415-022-11192-x",
"authors": [
- ["Marisa", "Cruz-Aguilar"],
- ["Caroline", "Guerrero-de Ferran"],
- ["Jose Luis", "Tovilla-Canales"],
- ["Angel", "Nava-Casta\u00f1eda"],
- ["Juan C", "Zenteno"]
+ ["Melissa", "Barghigiani"],
+ ["Giovanna", "De Michele"],
+ ["Alessandra", "Tessa"],
+ ["Tommasina", "Fico"],
+ ["Gemma", "Natale"],
+ ["Francesco", "Sacc\u00e0"],
+ ["Chiara", "Pane"],
+ ["Nunzia", "Cuomo"],
+ ["Anna", "De Rosa"],
+ ["Sabina", "Pappat\u00e0"],
+ ["Giuseppe", "De Michele"],
+ ["Filippo M", "Santorelli"],
+ ["Alessandro", "Filla"]
],
- "publisher": "Journal of investigative medicine : the official publication of the American Federation for Clinical Research",
- "issn": "1708-8267",
- "date": "2016-12-15",
- "abstract": "Oculopharyngeal muscular dystrophy (OPMD) is an autosomal-dominant, adult-onset disorder defined by blepharoptosis, dysphagia, and proximal muscle weakness. OPMD arises from heterozygous expansions of a trinucleotide (GCN) tract situated at the 5' region of the polyadenylate RNA binding protein 1 (",
+ "publisher": "Journal of neurology",
+ "issn": "1432-1459",
+ "date": "2022-05-28",
+ "abstract": "We screened 62 late-onset ataxia patients for the AAGGG pathological expansion in the RFC-1 gene that, when biallelic, causes Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome (CANVAS). Nine patients tested positive. Six had a previous diagnosis of sporadic adult-onset ataxia (SAOA) and three of multisystem atrophy type C (MSA-C). Further six patients were heterozygous for the pathological RFC-1 expansion, four with an initial diagnosis of MSA-C and two of SAOA. In comparison with CANVAS, MSA-C patients had faster progression and shorter disease duration to walking with aids. An abnormal DaTscan does not seem to contribute to differential diagnosis between CANVAS and MSA-C.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27980005"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35633373"
},
{
- "id": "pmid:26428746",
+ "id": "pmid:35585435",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26428746",
- "title": "A South African family with oculopharyngeal muscular dystrophy: Clinical and molecular genetic characteristics.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/35585435",
+ "title": "Beyond canvas: behavioral onset of rfc1-expansion disease in an Italian family-causal or casual?",
"type": "article-journal",
- "doi": "10.7196/samjnew.7880",
+ "doi": "10.1007/s10072-022-06137-1",
"authors": [
- ["Clara Maria", "Schutte"],
- ["Cecelia M", "Dorfling"],
- ["Riaan", "van Coller"],
- ["Engela M", "Honey"],
- ["Elizabeth Jansen", "van Rensburg"]
+ ["Fabiana", "Colucci"],
+ ["Daniela", "Di Bella"],
+ ["Chiara", "Pisciotta"],
+ ["Elisa", "Sarto"],
+ ["Francesca", "Gualandi"],
+ ["Marcella", "Neri"],
+ ["Alessandra", "Ferlini"],
+ ["Elena", "Contaldi"],
+ ["Maura", "Pugliatti"],
+ ["Davide", "Pareyson"],
+ ["Mariachiara", "Sensi"]
],
- "publisher": "South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde",
- "issn": "0256-9574",
- "date": "2015-09-21",
- "abstract": "Autosomal dominantly inherited oculopharyngeal muscular dystrophy (OPMD) is caused by a trinucleotide repeat expansion in exon 1 of the polyadenylate binding protein nuclear 1 (PABPN1) gene on chromosome 14q. A large family with OPMD was recently identified in Pretoria, South Africa (SA). Molecular studies revealed a (GCG)11(GCA)3GCG or (GCN)15 mutant allele. The (GCN)15 mutation detected in this family has been described previously in families from Uruguay and Mexico as a founder effect. To our knowledge, this is the first report of an SA Afrikaner family with molecularly confirmed OPMD. The proband, a 64-year-old woman, presented to the neurology outpatient department at Steve Biko Academic Hospital, Pretoria. A sibship of 18 individuals was identified, of whom eight had OPMD. Four patients were interviewed and examined clinically, and electromyographic studies were performed. Molecular analysis of the PABPN1 gene was performed by polymerase chain reaction amplification and direct sequencing of exon 1 in three of the patients. Patients presented with ptosis, external ophthalmoplegia, dysphagia, dysarthria and mild proximal weakness. High foot arches and absent ankle reflexes raised the possibility of peripheral neuropathy, but electromyography showed only mildly low sensory amplitudes, and myopathic units in two patients.",
+ "publisher": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology",
+ "issn": "1590-3478",
+ "date": "2022-05-18",
+ "abstract": "Biallelic intronic AAGGG repeat expansion in the replication factor C subunit 1 (RFC1) gene was recently identified in two/third of patients with cerebellar ataxia, sensory neuropathy, and bilateral vestibular areflexia syndrome (CANVAS). The phenotypic spectrum has expanded since (i.e., parkinsonism, motor neuron involvement, cognitive decline); no behavioral symptoms have been reported yet.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26428746"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35585435"
},
{
- "id": "pmid:23793615",
+ "id": "pmid:34968871",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23793615",
- "title": "A decline in PABPN1 induces progressive muscle weakness in oculopharyngeal muscle dystrophy and in muscle aging.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/34968871",
+ "title": "Cramp-fasciculation syndrome phenotype of cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) due to RFC1 repeat expansion.",
"type": "article-journal",
- "doi": "10.18632/aging.100567",
+ "doi": "10.1016/j.clinph.2021.11.005",
"authors": [
- ["Seyed Yahya", "Anvar"],
- ["Yotam", "Raz"],
- ["Nisha", "Verway"],
- ["Barbara", "van der Sluijs"],
- ["Andrea", "Venema"],
- ["Jelle J", "Goeman"],
- ["John", "Vissing"],
- ["Silv\u00e8re M", "van der Maarel"],
- ["Peter A C", "'t Hoen"],
- ["Baziel G M", "van Engelen"],
- ["Vered", "Raz"]
+ ["Hugo", "Kermorvant"],
+ ["Rabab", "Debs"],
+ ["Thierry", "Maisonobe"],
+ ["Vincent", "Huin"],
+ ["Tanya", "Stojkovic"],
+ ["Timoth\u00e9e", "Lenglet"]
],
- "publisher": "Aging",
- "issn": "1945-4589",
- "date": "2013-06-01",
- "abstract": "Oculopharyngeal muscular dystrophy (OPMD) is caused by trinucleotide repeat expansion mutations in Poly(A) binding protein 1 (PABPN1). PABPN1 is a regulator of mRNA stability and is ubiquitously expressed. Here we investigated how symptoms in OPMD initiate only at midlife and why a subset of skeletal muscles is predominantly affected. Genome-wide RNA expression profiles from Vastus lateralis muscles human carriers of expanded-PABPN1 at pre-symptomatic and symptomatic stages were compared with healthy controls. Major expression changes were found to be associated with age rather than with expression of expanded-PABPN1, instead transcriptomes of OPMD and elderly muscles were significantly similar (P<0.05). Using k-means clustering we identified age-dependent trends in both OPMD and controls, but trends were often accelerated in OPMD. We report an age-regulated decline in PABPN1 levels in Vastus lateralis muscles from the fifth decade. In concurrence with severe muscle degeneration in OPMD, the decline in PABPN1 accelerated in OPMD and was specific to skeletal muscles. Reduced PABPN1 levels (30% to 60%) in muscle cells induced myogenic defects and morphological signatures of cellular aging in proportion to PABPN1 expression levels. We suggest that PABPN1 levels regulate muscle cell aging and OPMD represents an accelerated muscle aging disorder.",
+ "publisher": "Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology",
+ "issn": "1872-8952",
+ "date": "2021-12-03",
+ "abstract": "",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23793615"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34968871"
},
{
- "id": "pmid:21647273",
+ "id": "pmid:33884451",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21647273",
- "title": "A GCG expansion (GCG)\u2081\u2081 in polyadenylate-binding protein nuclear 1 gene caused oculopharyngeal muscular dystrophy in a Chinese family.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/33884451",
+ "title": "RFC1 AAGGG repeat expansion masquerading as Chronic Idiopathic Axonal Polyneuropathy.",
"type": "article-journal",
- "doi": "",
+ "doi": "10.1007/s00415-021-10552-3",
"authors": [
- ["Juan", "Ye"],
- ["Huina", "Zhang"],
- ["Yandan", "Zhou"],
- ["Han", "Wu"],
- ["Changjun", "Wang"],
- ["Xin", "Shi"]
+ ["Matteo", "Tagliapietra"],
+ ["Davide", "Cardellini"],
+ ["Moreno", "Ferrarini"],
+ ["Silvia", "Testi"],
+ ["Sergio", "Ferrari"],
+ ["Salvatore", "Monaco"],
+ ["Tiziana", "Cavallaro"],
+ ["Gian Maria", "Fabrizi"]
],
- "publisher": "Molecular vision",
- "issn": "1090-0535",
- "date": "2011-05-25",
- "abstract": "To identify the mutation in polyadenylate-binding protein nuclear 1 gene (PABPN1, previously termed PABP2) in a Chinese family with autosomal, dominantly inherited oculopharyngeal muscular dystrophy (OPMD).",
+ "publisher": "Journal of neurology",
+ "issn": "1432-1459",
+ "date": "2021-04-21",
+ "abstract": "A biallelic intronic AAGGG repeat expansion in the Replication Factor C subunit 1 (RFC1) gene has been recently associated with Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome, a disorder often presenting as a slowly evolving sensory neuropathy at the onset. \"Chronic Idiopathic Axonal Polyneuropathy\" (CIAP) is a common indolent axonal neuropathy of adulthood which remains without an identifiable cause despite thorough investigations.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21647273"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33884451"
},
{
- "id": "pmid:21602480",
+ "id": "pmid:33807868",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21602480",
- "title": "Delayed diagnosis of oculopharyngeal muscular dystrophy in Scotland.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/33807868",
+ "title": "Whole-Genome Sequencing in Diagnostics of Selected Slovenian Undiagnosed Patients with Rare Disorders.",
"type": "article-journal",
- "doi": "10.1136/bjo.2010.200378",
+ "doi": "10.3390/life11030205",
"authors": [
- ["Pankaj Kumar", "Agarwal"],
- ["David C", "Mansfield"],
- ["Dorothy", "Mechan"],
- ["Rustam", "Al-Shahi Salman"],
- ["Richard J", "Davenport"],
- ["Myles", "Connor"],
- ["Richard", "Metcalfe"],
- ["Richard", "Petty"]
+ ["Gaber", "Bergant"],
+ ["Ale\u0161", "Maver"],
+ ["Borut", "Peterlin"]
],
- "publisher": "The British journal of ophthalmology",
- "issn": "1468-2079",
- "date": "2011-05-20",
- "abstract": "Oculopharyngeal muscular dystrophy (OPMD) presents with progressive ptosis, dysphagia and limb girdle weakness, and is caused by expansion of a trinucleotide tandem repeat within the gene encoding poly-(A) binding protein 2.",
+ "publisher": "Life (Basel, Switzerland)",
+ "issn": "2075-1729",
+ "date": "2021-03-05",
+ "abstract": "Several patients with rare genetic disorders remain undiagnosed following comprehensive diagnostic testing using whole-exome sequencing (WES). In these patients, pathogenic genetic variants may reside in intronic or regulatory regions or they may emerge through mutational mechanisms not detected by WES. For this reason, we implemented whole-genome sequencing (WGS) in routine clinical diagnostics of patients with undiagnosed genetic disorders and report on the outcome in 30 patients. Criteria for consideration included (1) negative WES, (2) a high likelihood of a genetic cause for the disorders, (3) positive family history, (4) detection of large blocks of homozygosity or (5) detection of a single pathogenic variant in a gene associated with recessive conditions. We successfully discovered a causative genetic variant in 6 cases, a retrotranspositional event in the APC gene, non-coding variants in the intronic region of the OTC gene and the promotor region of the UFM1 gene, repeat expansion in the RFC1 gene and a single exon duplication in the CNGB3 gene. We also discovered one coding variant, an indel, which was missed by variant caller during WES data analysis. Our study demonstrates the impact of WGS in the group of patients with undiagnosed genetic diseases after WES in the clinical setting and the diversity of mutational mechanisms discovered, which would remain undetected using other methods.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21602480"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33807868"
},
{
- "id": "pmid:21316245",
+ "id": "pmid:33068477",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21316245",
- "title": "Mutation and haplotype analysis of oculopharyngeal muscular dystrophy in Thai patients.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/33068477",
+ "title": "Dopa-Responsive Parkinsonism in a Patient With Homozygous RFC1 Expansions.",
"type": "article-journal",
- "doi": "10.1016/j.jocn.2010.08.020",
+ "doi": "10.1002/mds.28279",
"authors": [
- ["T", "Pulkes"],
- ["C", "Papsing"],
- ["M", "Busabaratana"],
- ["C", "Dejthevaporn"],
- ["R", "Witoonpanich"]
+ ["Roisin", "Sullivan"],
+ ["Wai Yan", "Yau"],
+ ["Viorica", "Chelban"],
+ ["Salvatore", "Rossi"],
+ ["Emer", "O'Connor"],
+ ["Nicholas W", "Wood"],
+ ["Andrea", "Cortese"],
+ ["Henry", "Houlden"]
],
- "publisher": "Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia",
- "issn": "1532-2653",
- "date": "2011-05-01",
- "abstract": "Oculopharyngeal muscular dystrophy (OPMD) is an inherited neuromuscular disease associated with a short trinucleotide repeat expansion in Exon 1 of the PABPN1 gene. OPMD is uncommon in East Asian populations, and there have been no previous reports of Thai patients. We studied clinical and molecular genetic features of six unrelated Thai patients with autosomal dominant OPMD. All patients had expansions of the guanine-cytosine-guanine (GCG) repeat ranging from three to seven additional repeats in the PABPN1 gene. Haplotype analysis showed that these mutations might have originated independently. Analysis of the size of the GCG repeat in the PABPN1 gene in 200 Thai control patients showed that 0.5% of the control subjects possessed (GCG)(7), thereby suggesting that the prevalence of autosomal recessive OPMD in the Thai population was approximately 1 in 160,000. In conclusion, our data suggest that OPMD in Thailand may be more common than previously thought.",
+ "publisher": "Movement disorders : official journal of the Movement Disorder Society",
+ "issn": "1531-8257",
+ "date": "2020-10-01",
+ "abstract": "",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21316245"
-},
-{
- "id": "pmid:18367172",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/18367172",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:18367172']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33068477"
},
{
- "id": "pmid:18343218",
+ "id": "pmid:33068476",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/18343218",
- "title": "Induction of expression and co-localization of heat shock polypeptides with the polyalanine expansion mutant of poly(A)-binding protein N1 after chemical stress.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/33068476",
+ "title": "Dopa-Responsive Parkinsonism in a Patient With Homozygous RFC1 Expansions.",
"type": "article-journal",
- "doi": "10.1016/j.bbrc.2008.02.162",
+ "doi": "10.1002/mds.28286",
"authors": [
- ["Qishan", "Wang"],
- ["Jnanankur", "Bag"]
+ ["Gabriel", "da Silva Schmitt"],
+ ["Alberto R M", "Martinez"],
+ ["Felipe F", "da Gra\u00e7a"],
+ ["Fabr\u00edcio Diniz", "de Lima"],
+ ["Luciana C", "Bonadia"],
+ ["B\u00e1rbara Juarez", "Amorim"],
+ ["Anamarli", "Nucci"],
+ ["Marcondes Cavalcante", "Fran\u00e7a"]
],
- "publisher": "Biochemical and biophysical research communications",
- "issn": "1090-2104",
- "date": "2008-03-14",
- "abstract": "Formation of nuclear inclusions consisting of aggregates of a polyalanine expansion mutant of nuclear poly(A)-binding protein (PABPN1) is the hallmark of oculopharyngeal muscular dystrophy (OPMD). OPMD is a late onset autosomal dominant disease. Patients with this disorder exhibit progressive swallowing difficulty and drooping of their eye lids, which starts around the age of 50. Previously we have shown that treatment of cells expressing the mutant PABPN1 with a number of chemicals such as ibuprofen, indomethacin, ZnSO(4), and 8-hydroxy-quinoline induces HSP70 expression and reduces PABPN1 aggregation. In these studies we have shown that expression of additional HSPs including HSP27, HSP40, and HSP105 were induced in mutant PABPN1 expressing cells following exposure to the chemicals mentioned above. Furthermore, all three additional HSPs were translocated to the nucleus and probably helped to properly fold the mutant PABPN1 by co-localizing with this protein.",
+ "publisher": "Movement disorders : official journal of the Movement Disorder Society",
+ "issn": "1531-8257",
+ "date": "2020-10-01",
+ "abstract": "",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18343218"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33068476"
},
{
- "id": "pmid:17138075",
+ "id": "pmid:32694621",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/17138075",
- "title": "Identification of a novel mutation in a Korean patient with oculopharyngeal muscular dystrophy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/32694621",
+ "title": "RFC1 repeat expansion in Japanese patients with late-onset cerebellar ataxia.",
"type": "article-journal",
- "doi": "10.1016/j.jocn.2005.12.036",
+ "doi": "10.1038/s10038-020-0807-x",
"authors": [
- ["Jong Seok", "Bae"],
- ["Chang-Seok", "Ki"],
- ["Jong-Won", "Kim"],
- ["Byoung Joon", "Kim"]
+ ["Mai", "Tsuchiya"],
+ ["Haitian", "Nan"],
+ ["Kishin", "Koh"],
+ ["Yuta", "Ichinose"],
+ ["Lihua", "Gao"],
+ ["Keisuke", "Shimozono"],
+ ["Takanori", "Hata"],
+ ["Yeon-Jeong", "Kim"],
+ ["Toshihisa", "Ohtsuka"],
+ ["Andrea", "Cortese"],
+ ["Yoshihisa", "Takiyama"]
],
- "publisher": "Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia",
- "issn": "0967-5868",
- "date": "2007-01-01",
- "abstract": "Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscle disorder characterized by progressive dysphagia and bilateral ptosis. Mutations in the polyadenylate binding protein nuclear 1 (PABPN1) gene have been found to cause OPMD. The typical mutation is a stable trinucleotide repeat expansion in the first exon of the PABPN1 gene, in which (GCG)(6) is the normal repeat length. We investigated a Korean patient with OPMD and identified a novel mutation: a heterozygous insertion of a 9-bp sequence [(GCG)(GCA)(GCA); c.27_28insGCGGCAGCA] instead of the (GCG) repeat expansion, resulting in an in-frame insertion of three alanines (p.A10insAAA). To the best of our knowledge, this is the first report of a genetically confirmed case of OPMD in Korea.",
+ "publisher": "Journal of human genetics",
+ "issn": "1435-232X",
+ "date": "2020-07-21",
+ "abstract": "Recently, the expansion of an intronic AAGGG repeat in the replication factor C subunit 1 (RFC1) gene was reported to cause cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). In Europeans, the expansion accounted for 22% of sporadic patients with late-onset ataxia. We genotyped 37 Japanese patients comprising 25 familial (autosomal recessive or undecided transmission) and 12 sporadic ones with late-onset ataxia. We found intronic repeat expansions in RFC1 in three (12%) of the familial patients and one (8.5%) of the sporadic ones. Although our cohort study was small, the disease frequency in Japanese patients with CANVAS might be lower than that in European ones. In addition, we found biallelic ACAGG repeat expansion in one patient, indicating ACAGG repeat expansion might cause CANVAS. Clinically, we found one patient with sleep apnea syndrome, which has not been reported previously. Thus, this study might expand the clinical and genetic spectrum of CANVAS.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17138075"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32694621"
},
{
- "id": "pmid:16378590",
+ "id": "pmid:32682126",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/16378590",
- "title": "Ectopic expression of a polyalanine expansion mutant of poly(A)-binding protein N1 in muscle cells in culture inhibits myogenesis.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/32682126",
+ "title": "False-positive anti-neuronal nuclear antibody type 1 in a patient with RFC1 repeat expansion: Preventing \"phenotype creep\" in autoimmune neurology.",
"type": "article-journal",
- "doi": "10.1016/j.bbrc.2005.12.078",
+ "doi": "10.1016/j.jns.2020.117018",
"authors": [
- ["Qishan", "Wang"],
- ["Jnanankur", "Bag"]
+ ["Adrian", "Budhram"],
+ ["John R", "Mills"],
+ ["Kamal", "Shouman"],
+ ["P James B", "Dyck"],
+ ["Anhar", "Hassan"],
+ ["Nicholas L", "Zalewski"]
],
- "publisher": "Biochemical and biophysical research communications",
- "issn": "0006-291X",
- "date": "2005-12-21",
- "abstract": "Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset dominant genetic disease caused by the expansion of a GCG trinucleotide repeat that encodes the polyalanine tract at the N-terminus of the nuclear poly(A)-binding protein (PABPN1). Presence of intranuclear inclusions (INIs) containing PABPN1 aggregates in the skeletal muscles is the hallmark of OPMD. Here, we show that ectopic expression of the mutant PABPN1 produced INIs in a muscle cell culture model and reduced expression of several muscle-specific proteins including alpha-actin, slow troponin C, muscle creatine kinase, and two myogenic transcription factors, myogenin and MyoD. However, the levels of two upstream regulators of the MyoD gene, the Myf-5 and Pax3/7, were not affected, but both proteins co-localized with the PABPN1 aggregates in the mutant PABPN1 overexpressing cells. In these cells, although myogenin and MyoD levels were reduced, these two transcription factors did not co-localize with the mutant PABPN1 aggregates. Therefore, sequestration of Myf5 and Pax3/7 by the mutant PABPN1 aggregates was a specific effect on these factors. Our results suggest that trapping of these two important myogenic determinants may interfere with an early step in myogenesis.",
+ "publisher": "Journal of the neurological sciences",
+ "issn": "1878-5883",
+ "date": "2020-07-09",
+ "abstract": "",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16378590"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32682126"
},
{
- "id": "pmid:16239242",
+ "id": "pmid:30926972",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/16239242",
- "title": "Induction of HSP70 expression and recruitment of HSC70 and HSP70 in the nucleus reduce aggregation of a polyalanine expansion mutant of PABPN1 in HeLa cells.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30926972",
+ "title": "Biallelic expansion of an intronic repeat in RFC1 is a common cause of late-onset ataxia.",
"type": "article-journal",
- "doi": "10.1093/hmg/ddi395",
+ "doi": "10.1038/s41588-019-0372-4",
"authors": [
- ["Qishan", "Wang"],
- ["Dick D", "Mosser"],
- ["Jnanankur", "Bag"]
+ ["Andrea", "Cortese"],
+ ["Roberto", "Simone"],
+ ["Roisin", "Sullivan"],
+ ["Jana", "Vandrovcova"],
+ ["Huma", "Tariq"],
+ ["Wai Yan", "Yau"],
+ ["Jack", "Humphrey"],
+ ["Zane", "Jaunmuktane"],
+ ["Prasanth", "Sivakumar"],
+ ["James", "Polke"],
+ ["Muhammad", "Ilyas"],
+ ["Eloise", "Tribollet"],
+ ["Pedro J", "Tomaselli"],
+ ["Grazia", "Devigili"],
+ ["Ilaria", "Callegari"],
+ ["Maurizio", "Versino"],
+ ["Vincenzo", "Salpietro"],
+ ["Stephanie", "Efthymiou"],
+ ["Diego", "Kaski"],
+ ["Nick W", "Wood"],
+ ["Nadja S", "Andrade"],
+ ["Elena", "Buglo"],
+ ["Adriana", "Rebelo"],
+ ["Alexander M", "Rossor"],
+ ["Adolfo", "Bronstein"],
+ ["Pietro", "Fratta"],
+ ["Wilson J", "Marques"],
+ ["Stephan", "Z\u00fcchner"],
+ ["Mary M", "Reilly"],
+ ["Henry", "Houlden"]
],
- "publisher": "Human molecular genetics",
- "issn": "0964-6906",
- "date": "2005-10-20",
- "abstract": "Nuclear inclusions formed by the aggregation of a polyalanine expansion mutant of the nuclear poly(A)-binding protein (PABPN1) is a hallmark of oculopharyngeal muscular dystrophy (OPMD). OPMD is a dominant autosomal disease in which patients exhibit progressive difficulty of swallowing and eyelid elevation, starting around the age of 50. At present, there is no specific treatment to reduce the aggregate burden in patients. However, in cell culture models of OPMD, reduction of protein aggregation can be achieved by ectopic expression of HSP70. As gene transfer may not be the most effective means to elevate HSP70 levels, we tested four pharmacological agents for their ability to induce HSP70, recruit both HSP70 and HSC70 into the cell nucleus and reduce mutant PABPN1 aggregation in a HeLa cell culture model. We show here that exposure to moderate levels of ZnSO4, 8-hydroxyquinoline, ibuprofen and indomethacin produced a robust stress response resulting in the induction of HSP70 in HeLa cells expressing the mutant PABPN1 as a green fluorescent protein (GFP) fusion protein. Both HSP70 and the constitutive chaperone HSC70 localized in the nucleus of cells treated with any one of the four agents. This stress response was similar to what was observed following hyperthermia. All four agents also caused a significant reduction in the cellular burden of protein aggregates, as was judged by confocal microscopy and solubility changes of the aggregates. A concomitant reduction of cell death in drug-treated mutant PABPN1 expressing cells was also observed.",
+ "publisher": "Nature genetics",
+ "issn": "1546-1718",
+ "date": "2019-03-29",
+ "abstract": "Late-onset ataxia is common, often idiopathic, and can result from cerebellar, proprioceptive, or vestibular impairment; when in combination, it is also termed cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). We used non-parametric linkage analysis and genome sequencing to identify a biallelic intronic AAGGG repeat expansion in the replication factor C subunit 1 (RFC1) gene as the cause of familial CANVAS and a frequent cause of late-onset ataxia, particularly if sensory neuronopathy and bilateral vestibular areflexia coexist. The expansion, which occurs in the poly(A) tail of an AluSx3 element and differs in both size and nucleotide sequence from the reference (AAAAG)",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16239242"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30926972"
},
{
- "id": "pmid:15811916",
+ "id": "pmid:12556494",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/15811916",
- "title": "In vivo aggregation properties of the nuclear poly(A)-binding protein PABPN1.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/12556494",
+ "title": "Replication and expansion of trinucleotide repeats in yeast.",
"type": "article-journal",
- "doi": "10.1261/rna.7217105",
+ "doi": "10.1128/mcb.23.4.1349-1357.2003",
"authors": [
- ["Jo\u00e3o Paulo", "Tavanez"],
- ["Patricia", "Calado"],
- ["Jos\u00e9", "Braga"],
- ["Miguel", "Lafarga"],
- ["Maria", "Carmo-Fonseca"]
+ ["Richard", "Pelletier"],
+ ["Maria M", "Krasilnikova"],
+ ["George M", "Samadashwily"],
+ ["Robert", "Lahue"],
+ ["Sergei M", "Mirkin"]
],
- "publisher": "RNA (New York, N.Y.)",
- "issn": "1355-8382",
- "date": "2005-04-05",
- "abstract": "A broad range of degenerative diseases is associated with intracellular inclusions formed by toxic, aggregation-prone mutant proteins. Intranuclear inclusions constitute a pathological hallmark of oculopharyngeal muscular dystrophy (OPMD), a dominantly inherited disease caused by (GCG) repeat expansions in the gene that encodes for nuclear poly(A) binding protein (PABPN1). The mutation results in an extended polyalanine stretch that has been proposed to induce protein aggregation and formation of intranuclear inclusions. Here we show that normal PABPN1 is inherently aggregation-prone when exogenously expressed in either HeLa or myogenic C2 cells. Similar deposits of insoluble PABPN1 are formed by variant forms of the protein containing either a polyalanine expansion or a complete deletion of the polyalanine tract, indicating that the mutation responsible for OPMD is not essential for formation of PABPN1 inclusions. In contrast, interfering with any of the protein domains required for stimulation of poly(A) polymerase prevents the formation of inclusions. Most surprisingly, photobleaching experiments reveal that both normal and expanded PABPN1 molecules are not irreversibly sequestered into aggregates, but rather move rapidly in and out of the inclusions. These findings have important implications for the interpretation of OPMD model systems based on exogenous expression of PABPN1.",
+ "publisher": "Molecular and cellular biology",
+ "issn": "0270-7306",
+ "date": "2003-02-01",
+ "abstract": "The mechanisms of trinucleotide repeat expansions, underlying more than a dozen hereditary neurological disorders, are yet to be understood. Here we looked at the replication of (CGG)(n) x (CCG)(n) and (CAG)(n) x (CTG)(n) repeats and their propensity to expand in Saccharomyces cerevisiae. Using electrophoretic analysis of replication intermediates, we found that (CGG)(n) x (CCG)(n) repeats significantly attenuate replication fork progression. Replication inhibition for this sequence becomes evident at as few as approximately 10 repeats and reaches a maximal level at 30 to 40 repeats. This is the first direct demonstration of replication attenuation by a triplet repeat in a eukaryotic system in vivo. For (CAG)(n) x (CTG)(n) repeats, on the contrary, there is only a marginal replication inhibition even at 80 repeats. The propensity of trinucleotide repeats to expand was evaluated in a parallel genetic study. In wild-type cells, expansions of (CGG)(25) x (CCG)(25) and (CAG)(25) x (CTG)(25) repeat tracts occurred with similar low rates. A mutation in the large subunit of the replicative replication factor C complex (rfc1-1) increased the expansion rate for the (CGG)(25) repeat approximately 50-fold but had a much smaller effect on the expansion of the (CTG)(25) repeat. These data show dramatic sequence-specific expansion effects due to a mutation in the lagging strand DNA synthesis machinery. Together, the results of this study suggest that expansions are likely to result when the replication fork attempts to escape from the stall site.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15811916"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12556494"
},
{
- "id": "pmid:14627730",
+ "id": "pmid:39044557",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/14627730",
- "title": "Trinucleotide expansions leading to an extended poly-L-alanine segment in the poly (A) binding protein PABPN1 cause fibril formation.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/39044557",
+ "title": "Clinical and pathological characteristics of OPDM4 patients in advanced disease.",
"type": "article-journal",
- "doi": "10.1110/ps.03214703",
+ "doi": "10.1002/mus.28200",
"authors": [
- ["Till", "Scheuermann"],
- ["Barbe", "Schulz"],
- ["Alfred", "Blume"],
- ["Elmar", "Wahle"],
- ["Rainer", "Rudolph"],
- ["Elisabeth", "Schwarz"]
+ ["Haixia", "Tang"],
+ ["Ying", "Xiong"],
+ ["Kaiyan", "Jiang"],
+ ["Yu", "Shen"],
+ ["Yanyan", "Yu"],
+ ["Pengcheng", "Huang"],
+ ["Min", "Zhu"],
+ ["Xiaobing", "Li"],
+ ["Yilei", "Zheng"],
+ ["Meihong", "Zhou"],
+ ["Jiaxi", "Yu"],
+ ["Jianwen", "Deng"],
+ ["Zhaoxia", "Wang"],
+ ["Daojun", "Hong"],
+ ["Yusen", "Qiu"],
+ ["Dandan", "Tan"]
],
- "publisher": "Protein science : a publication of the Protein Society",
- "issn": "0961-8368",
- "date": "2003-12-01",
- "abstract": "The nuclear poly(A) binding protein (PABPN1) stimulates poly(A) polymerase and controls the lengths of poly(A) tails during pre-mRNA processing. The wild-type protein possesses 10 consecutive Ala residues immediately after the start methionine. Trinucleotide expansions in the coding sequence result in an extension of the Ala stretch to maximal 17 Ala residues in total. Individuals carrying the trinucleotide expansions suffer from oculopharyngeal muscular dystrophy (OPMD). Intranuclear inclusions consisting predominantly of PABPN1 have been recognized as a pathological hallmark of the genetic disorder. To elucidate the molecular events that lead to disease, recombinant PABPN1, and N-terminal fragments of the protein with varying poly-L-alanine stretches were analyzed. As the full-length protein displayed a strong tendency to aggregate into amorphous deposits, soluble N-terminal fragments were also studied. Expansion of the poly-L-alanine sequence to the maximal length observed in OPMD patients led to an increase of alpha-helical structure. Upon prolonged incubation the protein was found in fibrils that showed all characteristics of amyloid-like fibers. The lag-phase of fibril formation could be reduced by seeding. Structural analysis of the fibrils indicated antiparallel beta-sheets.",
- "language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:14627730"
-},
-{
- "id": "pmid:12673802",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/12673802",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:12673802']' timed out after 3 seconds"
+ "publisher": "Muscle & nerve",
+ "issn": "1097-4598",
+ "date": "2024-07-23",
+ "abstract": "Oculopharyngodistal myopathy type 4 (OPDM4) arises from a CGG repeat expansion in the 5' UTR of the RILPL1 gene. Reported cases of OPDM4 have been limited. The aim of this study was to investigate the clinical and myopathological characteristics of OPDM4 patients with advanced disease.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39044557"
},
{
- "id": "pmid:11712939",
+ "id": "pmid:19264154",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/11712939",
- "title": "Oculopharyngeal muscular dystrophy in Hispanic New Mexicans.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19264154",
+ "title": "The polycystic kidney disease 1 (Pkd1) gene is required for the responses of osteochondroprogenitor cells to midpalatal suture expansion in mice.",
"type": "article-journal",
- "doi": "10.1001/jama.286.19.2437",
+ "doi": "10.1016/j.bone.2009.02.018",
"authors": [
- ["M W", "Becher"],
- ["L", "Morrison"],
- ["L E", "Davis"],
- ["W C", "Maki"],
- ["M K", "King"],
- ["J M", "Bicknell"],
- ["B L", "Reinert"],
- ["C", "Bartolo"],
- ["D G", "Bear"]
+ ["Bo", "Hou"],
+ ["Elona", "Kolpakova-Hart"],
+ ["Naomi", "Fukai"],
+ ["Kimberly", "Wu"],
+ ["Bjorn R", "Olsen"]
],
- "publisher": "JAMA",
- "issn": "0098-7484",
- "date": "2001-11-21",
- "abstract": "Oculopharyngeal muscular dystrophy (OPMD) is a rare myopathy caused by polyalanine triplet repeat expansion in the gene for poly(A) binding protein 2 (PABP2) and is found in isolated cohorts throughout the world. We have observed numerous cases of OPMD in New Mexico.",
+ "publisher": "Bone",
+ "issn": "1873-2763",
+ "date": "2009-03-02",
+ "abstract": "Mechanical stress is known to modulate postnatal skeletal growth and development. However, the mechanisms underlying the mechanotransduction are not fully understood. Polycystin-1 (PC1) is a promising candidate among proteins that may play a role in the process as it has been shown to function as a flow sensor in renal epithelium and it is known to be important for skeletal development. To investigate whether PC1 is involved in mechanotransduction in skeletal tissues, mice with a conditional deficiency for PC1 in neural crest cells, osteoblasts or chondrocytes were subjected to midpalatal suture expansion. Dynamic bone labeling revealed that new bone formation in response to expansion was significantly reduced in Wnt1Cre;Pkd1 mice, as the suture area containing new bone was 14.0+/-3.4% in mutant mice versus 65.0+/-3.8% in control mice at 2 weeks (p<0.001). In contrast, stress-induced new bone formation was not affected in OsxCre;Pkd1 mice. The increase in cell proliferation and differentiation into osteoblasts, seen in wild-type mice 1 day after force delivery, was not observed until 14 days in Wnt1Cre;Pkd1 mice. TUNEL labeling showed a significant increase in apoptotic suture cells at days 1 and 3 (from 7.0+/-0.5% to 13.5+/-1.4% at day 1 and from 4.6+/-1.1% to 10.5+/-1.7% at day 3, p<0.05). Abnormal ossification of nasal cartilage of Wnt1Cre;Pkd1 mice was accelerated upon suture expansion. Such ossification was also observed, but to a lesser extent in Col2a1-ERCre;Pkd1 mice. Transcript levels of Runx2 and MMP13 were significantly increased in the nasal cartilage of Wnt1Cre;Pkd1 mice compared to controls (p<0.05 and p<0.001, respectively), and in mutant mice with expansion versus without expansion (p<0.05 and p<0.001, respectively). Lack of PC1 in chondroprogenitor cells also resulted in increased cell apoptosis and an altered arrangement of chondrocytes in nasal cartilage. These results indicate that PC1 plays a critical role in the response of osteochondroprogenitor cells to the mechanical tissue stress induced by midpalatal suture expansion. They also suggest that the combination of an in vivo mechanical model, such as midpalatal suture expansion, with conditional deficiency for proteins that play a role in mechanotransduction, represents a powerful experimental strategy to explore underlying mechanisms.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11712939"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19264154"
},
{
- "id": "pmid:11087766",
+ "id": "pmid:38467733",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/11087766",
- "title": "Oculopharyngeal MD among Bukhara Jews is due to a founder (GCG)9 mutation in the PABP2 gene.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38467733",
+ "title": "Origin and evolution of pentanucleotide repeat expansions at the familial cortical myoclonic tremor with epilepsy type1 - SAMD12 locus.",
"type": "article-journal",
- "doi": "10.1212/wnl.55.9.1267",
+ "doi": "10.1038/s41431-024-01586-y",
"authors": [
- ["S C", "Blumen"],
- ["A D", "Korczyn"],
- ["H", "Lavoie"],
- ["S", "Medynski"],
- ["J", "Chapman"],
- ["A", "Asherov"],
- ["P", "Nisipeanu"],
- ["R", "Inzelberg"],
- ["R L", "Carasso"],
- ["J P", "Bouchard"],
- ["F M", "Tom\u00e9"],
- ["G A", "Rouleau"],
- ["B", "Brais"]
+ ["Xinhui", "Chen"],
+ ["Fan", "Zhang"],
+ ["Yihua", "Shi"],
+ ["Haotian", "Wang"],
+ ["Miao", "Chen"],
+ ["Dehao", "Yang"],
+ ["Lebo", "Wang"],
+ ["Peng", "Liu"],
+ ["Fei", "Xie"],
+ ["Jiawen", "Chen"],
+ ["Aisi", "Fu"],
+ ["Ben", "Hu"],
+ ["Bo", "Wang"],
+ ["Zhiyuan", "Ouyang"],
+ ["Sheng", "Wu"],
+ ["Zhiru", "Lin"],
+ ["Zhidong", "Cen"],
+ ["Wei", "Luo"]
],
- "publisher": "Neurology",
- "issn": "0028-3878",
- "date": "2000-11-14",
- "abstract": "To determine whether all cases of oculopharyngeal muscular dystrophy (OPMD) among Bukhara Jews share the same founder mutation.",
+ "publisher": "European journal of human genetics : EJHG",
+ "issn": "1476-5438",
+ "date": "2024-03-12",
+ "abstract": "Familial cortical myoclonic tremor with epilepsy type 1 (FCMTE1) is caused by (TTTTA)exp(TTTCA)exp repeat expansions in SAMD12, while pure (TTTTA)exp is polymorphic. Our investigation focused on the origin and evolution of pure (TTTTA)exp and (TTTTA)exp(TTTCA)exp at this locus. We observed a founder effect between them. The phylogenetic analysis suggested that the (TTTTA)exp(TTTCA)exp might be generated from pure (TTTTA)exp through infrequent transformation events. Long-read sequencing revealed somatic generation of (TTTTA)exp(TTTCA)exp from pure (TTTTA)exp, likely via long segment (TTTCA) repeats insertion. Our findings indicate close relationships between the non-pathogenic (TTTTA)exp and the pathogenic (TTTTA)exp(TTTCA)exp, with dynamic interconversions. This sheds light on the genesis of pathogenic repeat expansions from ancestral premutation alleles. Our results may guide future studies in detecting novel repeat expansion disorders and elucidating repeat expansion mutational processes, thereby enhancing our understanding of human genomic variation.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11087766"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38467733"
},
{
- "id": "pmid:11003790",
+ "id": "pmid:33681653",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/11003790",
- "title": "Nuclear accumulation of expanded PABP2 gene product in oculopharyngeal muscular dystrophy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/33681653",
+ "title": "Clinical and genomic analysis of a large Chinese family with familial cortical myoclonic tremor with epilepsy and",
"type": "article-journal",
- "doi": "10.1002/1097-4598(200010)23:10<1549::aid-mus11>3.0.co;2-0",
+ "doi": "10.1002/epi4.12450",
"authors": [
- ["E", "Uyama"],
- ["T", "Tsukahara"],
- ["K", "Goto"],
- ["Y", "Kurano"],
- ["M", "Ogawa"],
- ["Y J", "Kim"],
- ["M", "Uchino"],
- ["K", "Arahata"]
+ ["Yongxing", "Zhou"],
+ ["Raman", "Sood"],
+ ["Qun", "Wang"],
+ ["Blake", "Carrington"],
+ ["Morgan", "Park"],
+ ["Alice C", "Young"],
+ ["Daniel", "Birnbaum"],
+ ["Zhao", "Liu"],
+ ["Tetsuo", "Ashizawa"],
+ ["James C", "Mullikin"],
+ ["Mohamad Z", "Koubeissi"],
+ ["Paul", "Liu"]
],
- "publisher": "Muscle & nerve",
- "issn": "0148-639X",
- "date": "2000-10-01",
- "abstract": "Autosomal dominant oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disease caused by (GCG) repeat expansions in exon 1 of the poly(A) binding protein 2 gene (PABP2). To elucidate the molecular mechanism underlying the disease, we raised an antiserum against a synthetic peptide fragment predicted from PABP2 cDNA. The peptide corresponded to amino acids 271-291 where a cluster of posttranslational arginine methylation occurs. We examined the subcellular localization of PABP2 in muscle specimens from five patients with OPMD, 14 patients with various neuromuscular disorders, and three normal controls. All Japanese patients with OPMD have been shown to have expanded (GCG)(8, 9, or 11) mutations in PABP2, as well as intranuclear tubulofilamentous inclusions (ITFI) of 8.5 nm. None of 50 separate Japanese control individuals were shown to have expanded (GCG) repeat in PABP2. Positive immunoreaction for polyclonal PABP2 was confined to the intranuclear aggregates of muscle fibers exclusively in patients with OPMD. Frequency of the nuclei positive for PABP2 (2%) was similar to that of ITFI detected by electron microscopy (2.5%). There was no apparent relationship between the frequency of PABP2-positive intranuclear aggregates and the severity of muscle fiber damage. In contrast, nuclear immunoreaction was not detected in any samples from normal controls or from other neuromuscular diseases. These results suggest the presence of molecular modification of the product of expanded (GCG) repeat in PABP2, since the synthetic antigen peptide may not recognize a highly dimethylated cluster of arginine residues of the native PABP2, but may recognize the mutated form. Nuclear accumulation of expanded PABP2 product implies a causative role for ITFI.",
+ "publisher": "Epilepsia open",
+ "issn": "2470-9239",
+ "date": "2021-02-02",
+ "abstract": "Our goal was to perform detailed clinical and genomic analysis of a large multigenerational Chinese family with 21 individuals showing symptoms of Familial Cortical Myoclonic Tremor with Epilepsy (FCMTE) that we have followed for over 20\u00a0years.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11003790"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33681653"
},
{
- "id": "pmid:10734263",
+ "id": "pmid:33501421",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/10734263",
- "title": "Oculopharyngeal muscular dystrophy in a Japanese family with a short GCG expansion (GCG)(11) in PABP2 gene.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/33501421",
+ "title": "Genomic analysis of patients in a South Indian Community with autosomal dominant cortical tremor, myoclonus and epilepsy suggests a founder repeat expansion mutation in the",
"type": "article-journal",
- "doi": "10.1016/s0960-8966(99)00104-2",
+ "doi": "10.1093/braincomms/fcaa214",
"authors": [
- ["T", "Nagashima"],
- ["H", "Kato"],
- ["M", "Kase"],
- ["S", "Maguchi"],
- ["Y", "Mizutani"],
- ["K", "Matsuda"],
- ["T", "Chuma"],
- ["Y", "Mano"],
- ["Y", "Goto"],
- ["N", "Minami"],
- ["I", "Nonaka"],
- ["K", "Nagashima"]
+ ["Radha", "Mahadevan"],
+ ["Rahul C", "Bhoyar"],
+ ["Natarajan", "Viswanathan"],
+ ["Raskin Erusan", "Rajagopal"],
+ ["Bobby", "Essaki"],
+ ["Varun", "Suroliya"],
+ ["Rachel", "Chelladurai"],
+ ["Saravanan", "Sankaralingam"],
+ ["Ganesan", "Shanmugam"],
+ ["Sriramakrishnan", "Vayanakkan"],
+ ["Uzma", "Shamim"],
+ ["Aradhana", "Mathur"],
+ ["Abhinav", "Jain"],
+ ["Mohamed", "Imran"],
+ ["Mohammed", "Faruq"],
+ ["Vinod", "Scaria"],
+ ["Sridhar", "Sivasubbu"],
+ ["Shantaraman", "Kalyanaraman"]
],
- "publisher": "Neuromuscular disorders : NMD",
- "issn": "0960-8966",
- "date": "2000-03-01",
- "abstract": "Clinicopathological and molecular genetic findings on a new Japanese family with oculopharyngeal muscular dystrophy are reported. The family has 54 members, ten of whom are affected (seven male and three female), in 3 generations. Three affected males, one affected female and one unaffected female of seven living siblings in the third generation were examined. Bilateral ptosis developed in the 4th and 5th decades in the three male cases, and in the 7th decade in the female, and this was followed by diplopia, nasal voice, dysphagia and muscle weakness. In addition, severe external ophthalmoplegia, dysphonia, and proximal amyotrophy were prominent in this family. Electromyographs revealed myogenic/neurogenic changes, and computed tomography disclosed selective muscle wasting with fatty replacement, predominantly in the lower extremities. Muscle biopsy in the four affected patients showed variation in fiber size, and the presence of small angulated fibers and occasional rimmed vacuoles. Electron microscopic examination revealed an accumulation of filamentous inclusions in muscle fiber nuclei. DNA analysis identified that (GCG)(6) in the PABP2 gene was expanded to (GCG)(11) in the four affected cases examined. All studies were negative in the one unaffected. These results confirm that OPMD is caused by GCG short expansion and provides insights into the genetic mechanisms which may contribute to adult onset myopathy, confined to oculopharyngeal muscles.",
+ "publisher": "Brain communications",
+ "issn": "2632-1297",
+ "date": "2020-12-19",
+ "abstract": "Autosomal Dominant Cortical Tremor, Myoclonus and Epilepsy is a non-progressive disorder characterized by distal tremors. Autosomal Dominant Cortical Tremor, Myoclonus and Epilepsy has been reported globally with different genetic predispositions of autosomal dominant inheritance with a high degree of penetrance. In south India, Autosomal Dominant Cortical Tremor, Myoclonus and Epilepsy has been reported in a large cohort of 48 families, in which the genetic defect was not identified. This report pertains to the whole-genome analysis of four individuals followed by repeat-primed PCR for 102 patients from a familial cohort of 325 individuals. All the patients underwent extensive clinical evaluation including neuropsychological examinations. The whole-genome sequencing was done for two affected and two unaffected individuals, belonging to two different families. The whole-genome sequencing analysis revealed the repeat expansion of TTTTA and TTTCA in intron 4 of the",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10734263"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33501421"
},
{
- "id": "pmid:38454954",
+ "id": "pmid:30559482",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/38454954",
- "title": "Pulmonary hypertension in an adult patient with congenital central hypoventilation syndrome: a case report.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30559482",
+ "title": "Detecting a long insertion variant in SAMD12 by SMRT sequencing: implications of long-read whole-genome sequencing for repeat expansion diseases.",
"type": "article-journal",
- "doi": "10.1093/ehjcr/ytae109",
+ "doi": "10.1038/s10038-018-0551-7",
"authors": [
- ["Yosuke", "Terui"],
- ["Shoko", "Ohura"],
- ["Tetsuji", "Nozaki"],
- ["Takuya", "Yagi"]
+ ["Takeshi", "Mizuguchi"],
+ ["Tomoko", "Toyota"],
+ ["Hiroaki", "Adachi"],
+ ["Noriko", "Miyake"],
+ ["Naomichi", "Matsumoto"],
+ ["Satoko", "Miyatake"]
],
- "publisher": "European heart journal. Case reports",
- "issn": "2514-2119",
- "date": "2024-02-26",
- "abstract": "Congenital central hypoventilation syndrome (CCHS) is a life-threatening disorder of autonomic respiratory control. Mutations in the paired-like homeobox 2B (PHOX2B) gene impair respiratory drive, causing hypercarbia and hypoxaemia. Most patients with CCHS are diagnosed in the neonatal period; however, a few are diagnosed in adulthood.",
+ "publisher": "Journal of human genetics",
+ "issn": "1435-232X",
+ "date": "2018-12-17",
+ "abstract": "Long-read sequencing technology is now capable of reading single-molecule DNA with an average read length of more than 10\u2009kb, fully enabling the coverage of large structural variations (SVs). This advantage may pave the way for the detection of unprecedented SVs as well as repeat expansions. Pathogenic SVs of only known genes used to be selectively analyzed based on prior knowledge of target DNA sequence. The unbiased application of long-read whole-genome sequencing (WGS) for the detection of pathogenic SVs has just begun. Here, we apply PacBio SMRT sequencing in a Japanese family with benign adult familial myoclonus epilepsy (BAFME). Our SV selection of low-coverage WGS data (7\u00d7) narrowed down the candidates to only six SVs in a 7.16-Mb region of the BAFME1 locus and correctly determined an approximately 4.6-kb SAMD12 intronic repeat insertion, which is causal of BAFME1. These results indicate that long-read WGS is potentially useful for evaluating all of the known SVs in a genome and identifying new disease-causing SVs in combination with other genetic methods to resolve the genetic causes of currently unexplained diseases.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38454954"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30559482"
},
{
- "id": "pmid:38431667",
+ "id": "pmid:40463055",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/38431667",
- "title": "Alternative low-populated conformations prompt phase transitions in polyalanine repeat expansions.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/40463055",
+ "title": "",
"type": "article-journal",
- "doi": "10.1038/s41467-024-46236-5",
+ "doi": "10.1101/2025.05.14.653432",
"authors": [
- ["Rosa", "Ant\u00f3n"],
- ["Miguel \u00c1", "Trevi\u00f1o"],
- ["David", "Pantoja-Uceda"],
- ["Sara", "F\u00e9lix"],
- ["Mar\u00eda", "Babu"],
- ["Eurico J", "Cabrita"],
- ["Markus", "Zweckstetter"],
- ["Philip", "Tinnefeld"],
- ["Andr\u00e9s M", "Vera"],
- ["Javier", "Oroz"]
+ ["Alan Mejia", "Maza"],
+ ["Madison", "Hincher"],
+ ["Kevin", "Correia"],
+ ["Tammy", "Gillis"],
+ ["Ayumi", "Nishiyama"],
+ ["Ellen B", "Penney"],
+ ["Aloysius", "Domingo"],
+ ["Rachita", "Yadav"],
+ ["Micaela G", "Murcar"],
+ ["Patrick D Villafria", "Mercado"],
+ ["Justin S", "Han"],
+ ["Ean P", "Norenberg"],
+ ["Cara", "Fernandez-Cerado"],
+ ["G Paul", "Legarda"],
+ ["Michelle", "Sy"],
+ ["Edwin", "Mu\u00f1oz"],
+ ["Mark C", "Ang"],
+ ["Cid Czarina E", "Diesta"],
+ ["Criscely", "Go"],
+ ["Nutan", "Sharma"],
+ ["D Cristopher", "Bragg"],
+ ["Michael E", "Talkowski"],
+ ["Marcy E", "MacDonald"],
+ ["Jong-Min", "Lee"],
+ ["Laurie J", "Ozelius"],
+ ["Vanessa Chantal", "Wheeler"]
],
- "publisher": "Nature communications",
- "issn": "2041-1723",
- "date": "2024-03-02",
- "abstract": "Abnormal trinucleotide repeat expansions alter protein conformation causing malfunction and contribute to a significant number of incurable human diseases. Scarce structural insights available on disease-related homorepeat expansions hinder the design of effective therapeutics. Here, we present the dynamic structure of human PHOX2B C-terminal fragment, which contains the longest polyalanine segment known in mammals. The major \u03b1-helical conformation of the polyalanine tract is solely extended by polyalanine expansions in PHOX2B, which are responsible for most congenital central hypoventilation syndrome cases. However, polyalanine expansions in PHOX2B additionally promote nascent homorepeat conformations that trigger length-dependent phase transitions into solid condensates that capture wild-type PHOX2B. Remarkably, HSP70 and HSP90 chaperones specifically seize PHOX2B alternative conformations preventing phase transitions. The precise observation of emerging polymorphs in expanded PHOX2B postulates unbalanced phase transitions as distinct pathophysiological mechanisms in homorepeat expansion diseases, paving the way towards the search of therapeutics modulating biomolecular condensates in central hypoventilation syndrome.",
+ "publisher": "bioRxiv : the preprint server for biology",
+ "issn": "2692-8205",
+ "date": "2025-05-16",
+ "abstract": "X-linked dystonia parkinsonism (XDP) is a progressive adult-onset neurogenerative disorder caused by the insertion of a SINE-VNTR-Alu (SVA) retrotransposon in",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38431667"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40463055"
},
{
- "id": "pmid:38001308",
+ "id": "pmid:38834915",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/38001308",
- "title": "Characteristics and outcomes in children with congenital central hypoventilation syndrome on long-term mechanical ventilation in the Netherlands.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38834915",
+ "title": "Mini-heterochromatin domains constrain the cis-regulatory impact of SVA transposons in human brain development and disease.",
"type": "article-journal",
- "doi": "10.1007/s00431-023-05339-9",
+ "doi": "10.1038/s41594-024-01320-8",
"authors": [
- ["E E", "Evers-Bikker"],
- ["W", "de Weerd"],
- ["P J", "Wijkstra"],
- ["L", "Corel"],
- ["L P", "Verweij"],
- ["B A H", "Vosse"]
+ ["Vivien", "Horv\u00e1th"],
+ ["Raquel", "Garza"],
+ ["Marie E", "J\u00f6nsson"],
+ ["Pia A", "Johansson"],
+ ["Anita", "Adami"],
+ ["Georgia", "Christoforidou"],
+ ["Ofelia", "Karlsson"],
+ ["Laura", "Castilla Vallmanya"],
+ ["Symela", "Koutounidou"],
+ ["Patricia", "Gerdes"],
+ ["Ninoslav", "Pandiloski"],
+ ["Christopher H", "Douse"],
+ ["Johan", "Jakobsson"]
],
- "publisher": "European journal of pediatrics",
- "issn": "1432-1076",
- "date": "2023-11-25",
- "abstract": "Congenital central hypoventilation syndrome (CCHS) is a rare condition characterized by central hypoventilation, leading to the majority of patients being dependent on ventilatory support during sleep. This condition is often accompanied by various associated symptoms, due to a PHOX2B gene variant involved in neuronal crest cell migration. This study is the first to review the characteristics and outcomes in children with CCHS on long-term mechanical ventilation in the Netherlands. We performed a retrospective study of all CCHS patients treated in the 4 Centers of Home Mechanical Ventilation of the University Medical Centers in the Netherlands from 2000 till 2022 by collecting information from the electronic medical records, documented during follow-up. We included 31 patients, out of which 27 exhibited a known genetic profile associated with CCHS, while no PHOX2B variant was identified in the remaining patients. Among the 27 patients with known genetic profiles, 10 patients had a non-polyalanine repeat expansion mutation (NPARM), followed by 20/27, 20/25, and 20/26 polyalanine repeat expansion mutations (PARMs) in descending order. The most common presentation involved respiratory failure or apneas during the neonatal period with an inability to wean off ventilation. The majority of patients required ventilatory support during sleep, with four patients experiencing life-threatening events related to this dependency. Daily use of ventilatory support varied among different genetic profiles. All genotypes reported comorbidities, with Hirschsprung's disease and cardiac arrhythmias being the most reported comorbidities. Notably, Hirschprung's disease was exclusively observed in patients with a 20/27 PHOX2B variant.",
+ "publisher": "Nature structural & molecular biology",
+ "issn": "1545-9985",
+ "date": "2024-06-04",
+ "abstract": "SVA (SINE (short interspersed nuclear element)-VNTR (variable number of tandem repeats)-Alu) retrotransposons remain active in humans and contribute to individual genetic variation. Polymorphic SVA alleles harbor gene regulatory potential and can cause genetic disease. However, how SVA insertions are controlled and functionally impact human disease is unknown. Here we dissect the epigenetic regulation and influence of SVAs in cellular models of X-linked dystonia parkinsonism (XDP), a neurodegenerative disorder caused by an SVA insertion at the TAF1 locus. We demonstrate that the KRAB zinc finger protein ZNF91 establishes H3K9me3 and DNA methylation over SVAs, including polymorphic alleles, in human neural progenitor cells. The resulting mini-heterochromatin domains attenuate the cis-regulatory impact of SVAs. This is critical for XDP pathology; removal of local heterochromatin severely aggravates the XDP molecular phenotype, resulting in increased TAF1 intron retention and reduced expression. Our results provide unique mechanistic insights into how human polymorphic transposon insertions are recognized and how their regulatory impact is constrained by an innate epigenetic defense system.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38001308"
-},
-{
- "id": "pmid:34012823",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/34012823",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:34012823']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38834915"
},
{
- "id": "pmid:33958749",
+ "id": "pmid:38616406",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/33958749",
- "title": "Paired-like homeobox gene (PHOX2B) nonpolyalanine repeat expansion mutations (NPARMs): genotype-phenotype correlation in congenital central hypoventilation syndrome (CCHS).",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38616406",
+ "title": "Stability of Mosaic Divergent Repeat Interruptions in X-Linked Dystonia-Parkinsonism.",
"type": "article-journal",
- "doi": "10.1038/s41436-021-01178-x",
+ "doi": "10.1002/mds.29809",
"authors": [
- ["Amy", "Zhou"],
- ["Casey M", "Rand"],
- ["Sara M", "Hockney"],
- ["Grace", "Niewijk"],
- ["Patrick", "Reineke"],
- ["Virginia", "Speare"],
- ["Elizabeth M", "Berry-Kravis"],
- ["Lili", "Zhou"],
- ["Lawrence J", "Jennings"],
- ["Min", "Yu"],
- ["Isabella", "Ceccherini"],
- ["Tiziana", "Bachetti"],
- ["Melanie", "Pennock"],
- ["Kai Lee", "Yap"],
- ["Debra E", "Weese-Mayer"]
+ ["Joshua", "La\u00df"],
+ ["Theresa", "L\u00fcth"],
+ ["Kathleen", "Schl\u00fcter"],
+ ["Susen", "Schaake"],
+ ["Bj\u00f6rn-Hergen", "Laabs"],
+ ["Christoph", "Much"],
+ ["Roland Dominic", "Jamora"],
+ ["Raymond L", "Rosales"],
+ ["Gerard", "Saranza"],
+ ["Cid Czarina E", "Diesta"],
+ ["Christopher E", "Pearson"],
+ ["Inke R", "K\u00f6nig"],
+ ["Norbert", "Br\u00fcggemann"],
+ ["Christine", "Klein"],
+ ["Ana", "Westenberger"],
+ ["Joanne", "Trinh"]
],
- "publisher": "Genetics in medicine : official journal of the American College of Medical Genetics",
- "issn": "1530-0366",
- "date": "2021-05-06",
- "abstract": "CCHS is an extremely rare congenital disorder requiring artificial ventilation as life support. Typically caused by heterozygous polyalanine repeat expansion mutations (PARMs) in the PHOX2B gene, identification of a relationship between PARM length and phenotype severity has enabled anticipatory management. However, for patients with non-PARMs in PHOX2B (NPARMs, ~10% of CCHS patients), a genotype-phenotype correlation has not been established. This comprehensive report of PHOX2B NPARMs and associated phenotypes, aims at elucidating potential genotype-phenotype correlations that will guide anticipatory management.",
+ "publisher": "Movement disorders : official journal of the Movement Disorder Society",
+ "issn": "1531-8257",
+ "date": "2024-04-14",
+ "abstract": "X-Linked dystonia-parkinsonism (XDP) is an adult-onset neurodegenerative disorder characterized by rapidly progressive dystonia and parkinsonism. Mosaic Divergent Repeat Interruptions affecting motif Length and Sequence (mDRILS) were recently found within the TAF1 SVA repeat tract and were shown to associate with repeat stability and age at onset in XDP, specifically the AGGG [5'-SINE-VNTR-Alu(AGAGGG)",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33958749"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38616406"
},
{
- "id": "pmid:33855005",
+ "id": "pmid:38835911",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/33855005",
- "title": "How the Management of Children With Congenital Central Hypoventilation Syndrome Has Changed Over Time: Two Decades of Experience From an Italian Center.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38835911",
+ "title": "Factors influencing reduced penetrance and variable expressivity in X-linked dystonia-parkinsonism.",
"type": "article-journal",
- "doi": "10.3389/fped.2021.648927",
+ "doi": "10.1515/medgen-2022-2135",
"authors": [
- ["Federica", "Porcaro"],
- ["Maria Giovanna", "Paglietti"],
- ["Claudio", "Cherchi"],
- ["Alessandra", "Schiavino"],
- ["Maria Beatrice", "Chiarini Testa"],
- ["Renato", "Cutrera"]
+ ["Jelena", "Pozojevic"],
+ ["Bj\u00f6rn-Hergen", "von Holt"],
+ ["Ana", "Westenberger"]
],
- "publisher": "Frontiers in pediatrics",
- "issn": "2296-2360",
- "date": "2021-03-29",
- "abstract": "",
+ "publisher": "Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V",
+ "issn": "1863-5490",
+ "date": "2022-08-12",
+ "abstract": "X-linked dystonia-parkinsonism (XDP) is a neurodegenerative movement disorder that primarily affects adult Filipino men. It is caused by a founder retrotransposon insertion in",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33855005"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38835911"
},
{
- "id": "pmid:30786110",
+ "id": "pmid:38835428",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/30786110",
- "title": "Novel PHOX2B mutations in congenital central hypoventilation syndrome.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38835428",
+ "title": "X-linked dystonia-parkinsonism: over and above a repeat disorder.",
"type": "article-journal",
- "doi": "10.1111/ped.13812",
+ "doi": "10.1515/medgen-2021-2105",
"authors": [
- ["Ayako", "Sasaki"],
- ["Yumiko", "Kishikawa"],
- ["Reisuke", "Imaji"],
- ["Yu", "Fukushima"],
- ["Yukiko", "Nakamura"],
- ["Yutaka", "Nishimura"],
- ["Megumi", "Yamada"],
- ["Yoichi", "Mino"],
- ["Tetsuo", "Mitsui"],
- ["Kiyoshi", "Hayasaka"]
+ ["Jelena", "Pozojevic"],
+ ["Joseph Neos", "Cruz"],
+ ["Ana", "Westenberger"]
],
- "publisher": "Pediatrics international : official journal of the Japan Pediatric Society",
- "issn": "1442-200X",
- "date": "2019-04-17",
- "abstract": "Congenital central hypoventilation syndrome (CCHS) is caused by mutation of paird-like homeobox 2B (PHOX2B). Approximately 90% of patients were found to carry polyalanine repeat expansion mutation (PARM), and the remaining 10% had non-PARM (NPARM). In PARM, the length of the polyalanine expansion correlates with clinical disease severity. Most patients with NPARM have hypoventilation symptoms in the neonatal period and complications of Hirschsprung disease, dysregulation of autonomic nervous system, and tumors of neural crest origin. Data on the genotype-phenotype association may contribute to the clinical management of the disease.",
+ "publisher": "Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V",
+ "issn": "1863-5490",
+ "date": "2022-01-12",
+ "abstract": "X-linked dystonia-parkinsonism (XDP) is an adult-onset neurodegenerative movement disorder, caused by a founder retrotransposon insertion in an intron of the",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30786110"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38835428"
},
{
- "id": "pmid:30672101",
+ "id": "pmid:34250228",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/30672101",
- "title": "Congenital central hypoventilation syndrome: Severe disease caused by co-occurrence of two PHOX2B variants inherited separately from asymptomatic family members.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/34250228",
+ "title": "Brain Regional Differences in Hexanucleotide Repeat Length in X-Linked Dystonia-Parkinsonism Using Nanopore Sequencing.",
"type": "article-journal",
- "doi": "10.1002/ajmg.a.61047",
+ "doi": "10.1212/nxg.0000000000000608",
"authors": [
- ["Yakov", "Sivan"],
- ["Amy", "Zhou"],
- ["Lawrence J", "Jennings"],
- ["Elizabeth M", "Berry-Kravis"],
- ["Min", "Yu"],
- ["Lili", "Zhou"],
- ["Casey M", "Rand"],
- ["Debra E", "Weese-Mayer"]
+ ["Charles Jourdan", "Reyes"],
+ ["Bj\u00f6rn-Hergen", "Laabs"],
+ ["Susen", "Schaake"],
+ ["Theresa", "L\u00fcth"],
+ ["Raphaela", "Ardicoglu"],
+ ["Aleksandar", "Rakovic"],
+ ["Karen", "Gr\u00fctz"],
+ ["Daniel", "Alvarez-Fischer"],
+ ["Roland Dominic", "Jamora"],
+ ["Raymond L", "Rosales"],
+ ["Imke", "Weyers"],
+ ["Inke R", "K\u00f6nig"],
+ ["Norbert", "Br\u00fcggemann"],
+ ["Christine", "Klein"],
+ ["Valerija", "Dobricic"],
+ ["Ana", "Westenberger"],
+ ["Joanne", "Trinh"]
],
- "publisher": "American journal of medical genetics. Part A",
- "issn": "1552-4833",
- "date": "2019-01-23",
- "abstract": "Congenital Central Hypoventilation Syndrome (CCHS) is a rare disease characterized by autonomic nervous system dysregulation. Central hypoventilation is the most prominent and clinically important presentation. CCHS is caused by mutations in paired-like homeobox 2b (PHOX2B) and is inherited in an autosomal dominant pattern. A co-occurrence of two asymptomatic PHOX2B variants with a classical CCHS presentation highlights the importance of clinical PHOX2B testing in parents and family members of all CCHS probands. Despite being an autosomal dominant disease, once a polyalanine repeat expansion mutation has been identified, sequencing of the other allele should also be considered.",
+ "publisher": "Neurology. Genetics",
+ "issn": "2376-7839",
+ "date": "2021-07-06",
+ "abstract": "Our study investigated the presence of regional differences in hexanucleotide repeat number in postmortem brain tissues of 2 patients with X-linked dystonia-parkinsonism (XDP), a combined dystonia-parkinsonism syndrome modified by a (CCCTCT)",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30672101"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34250228"
},
{
- "id": "pmid:30227298",
+ "id": "pmid:18952144",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/30227298",
- "title": "A novel PHOX2B gene mutation in an extremely low birth weight infant with congenital central hypoventilation syndrome and variant Hirschsprung's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18952144",
+ "title": "Genetic study of an American family with DYT3 dystonia (lubag).",
"type": "article-journal",
- "doi": "10.1016/j.ejmg.2018.09.008",
+ "doi": "10.1016/j.neulet.2008.10.049",
"authors": [
- ["Yuichiro", "Miura"],
- ["Tatsuya", "Watanabe"],
- ["Toshihiko", "Uchida"],
- ["Tatsuro", "Nawa"],
- ["Naobumi", "Endo"],
- ["Taichi", "Fukuzawa"],
- ["Ryuji", "Ohkubo"],
- ["Junji", "Takeyama"],
- ["Ayako", "Sasaki"],
- ["Kiyoshi", "Hayasaka"]
+ ["Hao", "Deng"],
+ ["Wei-Dong", "Le"],
+ ["Joseph", "Jankovic"]
],
- "publisher": "European journal of medical genetics",
- "issn": "1878-0849",
- "date": "2018-09-15",
- "abstract": "Congenital central hypoventilation syndrome is a disorder of respiratory control caused by mutations in the paired-like homeobox 2B gene. Mutations in the paired-like homeobox 2B gene are also responsible for Hirschsprung's disease. Variant Hirschsprung's disease is a rarer disorder that does not meet the diagnostic criteria of Hirschsprung's disease, although severe functional bowel obstruction persists. We present a case of an extremely low birth weight infant with congenital central hypoventilation syndrome and variant Hirschsprung's disease. A male infant who was diagnosed to have fetal growth restriction and polyhydramnios was delivered by emergency cesarean section at 30 weeks and 3 days of gestational age due to non-reassuring fetal status. The birth weight was 979\u202fg, and intensive care was started immediately following delivery. The patient exhibited refractory apnea and was diagnosed with congenital central hypoventilation syndrome by genetic testing of the paired-like homeobox 2B gene. The patient also exhibited refractory functional bowel obstruction and was diagnosed to have variant Hirschsprung's disease through pathological examination of his intestinal specimens. The patient grew slowly but surely with intensive care including mechanical ventilation and parenteral nutrition. However, the patient repeatedly suffered from sepsis and died of fungemia at 197 days of age. This is the first congenital central hypoventilation syndrome case that was accompanied with variant Hirschsprung's disease, and the paired-like homeobox 2B mutation detected in this case (NM_003924.3: c.441G\u202f>\u202fC; p.(Gln147His)) is novel. This case suggests that the paired-like homeobox 2B mutation causes not only congenital central hypoventilation syndrome and Hirschsprung's disease, but also variant Hirschsprung's disease in humans. It also highlights the extreme difficulty in treating premature infants with severe and prolonged functional bowel obstruction.",
+ "publisher": "Neuroscience letters",
+ "issn": "0304-3940",
+ "date": "2008-10-21",
+ "abstract": "X-linked dystonia-parkinsonism (XDP, DYT3), endemic in the Philippine island of Panay, is characterized by the clinical onset with dystonia followed by parkinsonism. We found a 35-year-old American male patient, originally from Panay with typical XDP, has a 2-year history of parkinsonism, dystonia, and tremor. Ancestral DYT3 haplotype and disease-specific SVA (short interspersed nuclear element, variable number of tandem repeats, and Alu composite) retrotransposon insertion were identified in the DYT3 proband and two female unaffected family members. No mutation(s) and expression changes in peripheral blood lymphocytes were observed in the TATA-binding protein-associated factor 1 gene (TAF1) or the chemokine CXC motif receptor 3 gene (CXCR3) of the proband or other DYT3 carriers. These findings indicate blood DNA test has a diagnostic utility and implications for genetic counseling in families with DYT3. In contrast, TAF1 and CXCR3 gene expression in peripheral blood lymphocytes is not a suitable surrogate disease marker for DYT3.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30227298"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18952144"
},
{
- "id": "pmid:27129232",
+ "id": "pmid:18713817",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/27129232",
- "title": "Alanine Expansions Associated with Congenital Central Hypoventilation Syndrome Impair PHOX2B Homeodomain-mediated Dimerization and Nuclear Import.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18713817",
+ "title": "Deoxyribonucleic acid profiling analysis of 40 human thyroid cancer cell lines reveals cross-contamination resulting in cell line redundancy and misidentification.",
"type": "article-journal",
- "doi": "10.1074/jbc.m115.679027",
+ "doi": "10.1210/jc.2008-1102",
"authors": [
- ["Simona", "Di Lascio"],
- ["Debora", "Belperio"],
- ["Roberta", "Benfante"],
- ["Diego", "Fornasari"]
+ ["Rebecca E", "Schweppe"],
+ ["Joshua P", "Klopper"],
+ ["Christopher", "Korch"],
+ ["Umarani", "Pugazhenthi"],
+ ["Miriam", "Benezra"],
+ ["Jeffrey A", "Knauf"],
+ ["James A", "Fagin"],
+ ["Laura A", "Marlow"],
+ ["John A", "Copland"],
+ ["Robert C", "Smallridge"],
+ ["Bryan R", "Haugen"]
],
- "publisher": "The Journal of biological chemistry",
- "issn": "1083-351X",
- "date": "2016-04-27",
- "abstract": "Heterozygous mutations of the human PHOX2B gene, a key regulator of autonomic nervous system development, lead to congenital central hypoventilation syndrome (CCHS), a neurodevelopmental disorder characterized by a failure in the autonomic control of breathing. Polyalanine expansions in the 20-residues region of the C terminus of PHOX2B are the major mutations responsible for CCHS. Elongation of the alanine stretch in PHOX2B leads to a protein with altered DNA binding, transcriptional activity, and nuclear localization and the possible formation of cytoplasmic aggregates; furthermore, the findings of various studies support the idea that CCHS is not due to a pure loss of function mechanism but also involves a dominant negative effect and/or toxic gain of function for PHOX2B mutations. Because PHOX2B forms homodimers and heterodimers with its paralogue PHOX2A in vitro, we tested the hypothesis that the dominant negative effects of the mutated proteins are due to non-functional interactions with the wild-type protein or PHOX2A using a co-immunoprecipitation assay and the mammalian two-hybrid system. Our findings show that PHOX2B forms homodimers and heterodimerizes weakly with mutated proteins, exclude the direct involvement of the polyalanine tract in dimer formation, and indicate that mutated proteins retain partial ability to form heterodimers with PHOX2A. Moreover, in this study, we investigated the effects of the longest polyalanine expansions on the homeodomain-mediated nuclear import, and our data clearly show that the expanded C terminus interferes with this process. These results provide novel insights into the effects of the alanine tract expansion on PHOX2B folding and activity.",
+ "publisher": "The Journal of clinical endocrinology and metabolism",
+ "issn": "0021-972X",
+ "date": "2008-08-19",
+ "abstract": "Cell lines derived from human cancers provide critical tools to study disease mechanisms and develop novel therapies. Recent reports indicate that up to 36% of cell lines are cross- contaminated.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27129232"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18713817"
},
{
- "id": "pmid:26063465",
+ "id": "pmid:17273961",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26063465",
- "title": "Genotype-phenotype relationship in Japanese patients with congenital central hypoventilation syndrome.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17273961",
+ "title": "Reduced neuron-specific expression of the TAF1 gene is associated with X-linked dystonia-parkinsonism.",
"type": "article-journal",
- "doi": "10.1038/jhg.2015.65",
+ "doi": "10.1086/512129",
"authors": [
- ["Tomoyuki", "Shimokaze"],
- ["Ayako", "Sasaki"],
- ["Toru", "Meguro"],
- ["Hisaya", "Hasegawa"],
- ["Yuka", "Hiraku"],
- ["Tetsushi", "Yoshikawa"],
- ["Yumiko", "Kishikawa"],
- ["Kiyoshi", "Hayasaka"]
+ ["Satoshi", "Makino"],
+ ["Ryuji", "Kaji"],
+ ["Satoshi", "Ando"],
+ ["Maiko", "Tomizawa"],
+ ["Katsuhito", "Yasuno"],
+ ["Satoshi", "Goto"],
+ ["Shinnichi", "Matsumoto"],
+ ["Maria Daisy", "Tabuena"],
+ ["Elma", "Maranon"],
+ ["Marita", "Dantes"],
+ ["Lillian V", "Lee"],
+ ["Kazumasa", "Ogasawara"],
+ ["Ikuo", "Tooyama"],
+ ["Hiroyasu", "Akatsu"],
+ ["Masataka", "Nishimura"],
+ ["Gen", "Tamiya"]
],
- "publisher": "Journal of human genetics",
- "issn": "1435-232X",
- "date": "2015-06-11",
- "abstract": "Examine the genotype-phenotype relationship in Japanese congenital central hypoventilation syndrome (CCHS) patients and estimate the incidence of CCHS in Japan. Subjects were 92 Japanese patients with PHOX2B mutations; 19 cases carried 25 polyalanine repeat expansion mutations (PARMs); 67 cases carried 26 or more PARMs; and 6 had non-PARMs (NPARMs). We collected clinical data in all patients and estimated the development or intelligent quotients only in the patients carrying 25 PARM. The estimated incidence of CCHS was greater than one case per 148\u2009000 births. Polyhydramnios was observed in three cases. Twelve infants exhibited depressed respiration at birth. In 19 cases carrying 25 PARM, the male-to-female ratio was ~3, no cases had Hirschsprung disease; 7 cases (37%) developed hypoventilation after the neonatal period, and 8 cases (42%) had mental retardation. In other 73 cases carrying 26 or more PARMs or NPARMs, male-to-female ratio was equal; patients frequently complicated with Hirschsprung disease and constipation, and all patients presented with hypoventilation in the neonatal period. Clinical symptoms were severe in most patients carrying long PARMs and NPARMs. In 25 PARM, additional genetic and/or epigenetic factors were required for CCHS development and male sex is likely a predisposing factor. The patients carrying 25 PARM frequently had mental retardation likely because they were not able to receive appropriate ventilation support following a definitive diagnosis owing to subtle and or irregular hypoventilation. Molecular diagnosis provides a definitive diagnosis and enables to receive appropriate ventilator support.",
+ "publisher": "American journal of human genetics",
+ "issn": "0002-9297",
+ "date": "2007-01-23",
+ "abstract": "X-linked dystonia-parkinsonism (XDP) is a movement disorder endemic to the Philippines. The disease locus, DYT3, has been mapped to Xq13.1. In a search for the causative gene, we performed genomic sequencing analysis, followed by expression analysis of XDP brain tissues. We found a disease-specific SVA (short interspersed nuclear element, variable number of tandem repeats, and Alu composite) retrotransposon insertion in an intron of the TATA-binding protein-associated factor 1 gene (TAF1), which encodes the largest component of the TFIID complex, and significantly decreased expression levels of TAF1 and the dopamine receptor D2 gene (DRD2) in the caudate nucleus. We also identified an abnormal pattern of DNA methylation in the retrotransposon in the genome from the patient's caudate, which could account for decreased expression of TAF1. Our findings suggest that the reduced neuron-specific expression of the TAF1 gene is associated with XDP.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26063465"
-},
-{
- "id": "pmid:26011159",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/26011159",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:26011159']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17273961"
},
{
- "id": "pmid:24135798",
+ "id": "pmid:7668293",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/24135798",
- "title": "An unusual cause of fetal hypomobility:congenital central hypoventilation syndrome associated with hirschsprung disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/7668293",
+ "title": "Assignment of the dystonia-parkinsonism syndrome locus, DYT3, to a small region within a 1.8-Mb YAC contig of Xq13.1.",
"type": "article-journal",
- "doi": "10.1007/s00431-013-2171-8",
+ "doi": "",
"authors": [
- ["Sybille", "De Montpellier"],
- ["Yves", "Sznajer"],
- ["Jeanne", "Amiel"],
- ["Genevieve", "Francois"],
- ["Marie-Cecile", "Nassogne"],
- ["Christian", "Debauche"],
- ["Isabelle", "Scheers"]
+ ["G", "Haberhausen"],
+ ["I", "Schmitt"],
+ ["A", "K\u00f6hler"],
+ ["U", "Peters"],
+ ["S", "Rider"],
+ ["J", "Chelly"],
+ ["J D", "Terwilliger"],
+ ["A P", "Monaco"],
+ ["U", "M\u00fcller"]
],
- "publisher": "European journal of pediatrics",
- "issn": "1432-1076",
- "date": "2013-10-18",
- "abstract": "Co-occurrence of congenital central hypoventilation syndrome and Hirschsprung disease is known as Haddad syndrome. Affected patients develop with variable expressivity a dysfunction of the autonomic nervous system. We report the natural history of a full-term newborn infant presenting multiple features of autonomic system dysfunction that were already noted antenatally. The presence of a nonpolyalanine repeat expansion mutation in the PHOX2B gene confirmed postnatally the diagnosis of Haddad syndrome. This case suggests that patients presenting with autonomic system dysfunction may already present signs of the disease during the fetal period. Furthermore, antenatal presentations may correlate with a more severe presentation of the disease. In conclusion, antenatal signs of dysautonomy should stimulate multidisciplinary prenatal approach to orientate proper postnatal intervention and facilitate treatment strategies.",
+ "publisher": "American journal of human genetics",
+ "issn": "0002-9297",
+ "date": "1995-09-01",
+ "abstract": "A YAC contig was constructed of Xq13.1 in order to sublocalize the X-linked dystonia-parkinsonism (XDP) syndrome locus, DYT3. The contig spans a region of approximately 1.8 Mb and includes loci DXS453/DXS348/IL2R gamma/GJB1/CCG1/DXS559. For the construction of the contig, nine sequence-tagged sites and four short tandem repeat polymorphisms (STRPs) were isolated. The STRPs, designated as 4704#6 (DXS7113), 4704#7 (DXS7114), 67601 (DXS7117), and B4Pst (DXS7119) were assigned to a region flanked by DXS348 proximally and by DXS559 distally. Their order was DXS348/4704 #6/4704 #7/67601/B4Pst/DXS559. They were applied to the analysis of allelic association and of haplotypes in 47 not-obviously-related XDP patients and in 105 Filipino male controls. The same haplotype was found at loci 67601 (DXS7117) and B4Pst (DXS7119) in 42 of 47 patients. This percentage of common haplotypes decreased at the adjacent loci. The findings, together with the previous demonstration of DXS559 being the distal flanking marker of DYT3, assign the disease locus to a small region in Xq13.1 defined by loci 67601 (DXS7117) and B4Pst (DXS7119). The location of DYT3 was born out by the application of a newly developed likelihood method for the analysis of linkage disequilibrium.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24135798"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7668293"
},
{
- "id": "pmid:23460545",
+ "id": "pmid:1518853",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23460545",
- "title": "Recurrence of CCHS associated PHOX2B poly-alanine expansion mutation due to maternal mosaicism.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/1518853",
+ "title": "Delineation of the dystonia-parkinsonism syndrome locus in Xq13.",
"type": "article-journal",
- "doi": "10.1002/ppul.22790",
+ "doi": "10.1073/pnas.89.17.8245",
"authors": [
- ["Tiziana", "Bachetti"],
- ["Marco", "Di Duca"],
- ["Matteo", "Della Monica"],
- ["Lidia", "Grappone"],
- ["Gioacchino", "Scarano"],
- ["Isabella", "Ceccherini"]
+ ["M B", "Graeber"],
+ ["K G", "Kupke"],
+ ["U", "M\u00fcller"]
],
- "publisher": "Pediatric pulmonology",
- "issn": "1099-0496",
- "date": "2013-03-04",
- "abstract": "Heterozygous in frame trinucleotide duplications within the PHOX2B gene, leading to poly-alanine expansions, cause Congenital Central Hypoventilation Syndrome. Here we report about a CCHS patient, carrying a +13Ala PHOX2B expansion, whose asymptomatic mother resulted with a low level of mosaicism for the same mutation in peripheral blood cells. Her second pregnancy ended with the spontaneous miscarriage of a fetus who had inherited the PHOX2B mutation, thus confirming germline mosaicism in the mother and the need of proper genetic counseling to CCHS families.",
+ "publisher": "Proceedings of the National Academy of Sciences of the United States of America",
+ "issn": "0027-8424",
+ "date": "1992-09-01",
+ "abstract": "The X chromosome-linked dystonia-parkinsonism syndrome (XDP) is a severe movement disorder, characterized by both dystonia and parkinsonism. XDP is a genetically homogeneous disorder. Known ancestry of all patients has been traced back to Panay, Philippines, where the disease probably originated from a single mutation (founder effect). The gene locus, DYT3, has been previously assigned to the proximal long arm of the X chromosome (Xq12-q21.1). Using four dinucleotide tandem repeat (DNTR) sequences from Xq13-derived yeast artificial chromosomes (YACs), we further delineate DYT3 within Xq13. Observation of a recombination event between DYT3 and DNTR locus 4548-7, derived from a YAC encompassing locus DXS56, establishes 4548-7 as a distal flanking marker. Assignment of DYT3 to a region in Xq13, flanked by loci 4548-7 and DXS159, is further supported by highly significant allelic association between DYT3 and a total of four DNTR loci--PY2-31, PY5-10, 4548-1, and 4548-7--located in a region defined by PGK1 and DXS56. /phi/ and /delta/ values were 0.82/0.35, 0.78/0.42, 0.65/0.34, and 0.88/0.58 for PY2-31, PY5-10, 4548-1, and 4548-7 at P less than 10(-2), P less than 10(-4), P less than 10(-3), and P less than 10(-6).",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23460545"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:1518853"
},
{
- "id": "pmid:23460419",
+ "id": "pmid:39680235",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23460419",
- "title": "Heterozygous 24-polyalanine repeats in the PHOX2B gene with different manifestations across three generations.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/39680235",
+ "title": "Case Series of Cerebellar Ataxia with Tremor Due to Heterozygous STUB1 Variants (SCA48) without TBP Expansions: Further Evidence for SCA48 as a Monogenic Disease.",
"type": "article-journal",
- "doi": "10.1002/ppul.22731",
+ "doi": "10.1007/s12311-024-01762-2",
"authors": [
- ["Piyaporn", "Chuen-im"],
- ["Shinawi", "Marwan"],
- ["Jodi", "Carter"],
- ["James", "Kemp"],
- ["Katherine", "Rivera-Spoljaric"]
+ ["Yan", "Zochowski"],
+ ["Kishore R", "Kumar"],
+ ["Matthew", "Katz"],
+ ["Paul", "Darveniza"],
+ ["Michel", "Tchan"],
+ ["Renee", "Smyth"],
+ ["Susan", "Tomlinson"],
+ ["Kathy H C", "Wu"],
+ ["Stephen", "Tisch"]
],
- "publisher": "Pediatric pulmonology",
- "issn": "1099-0496",
- "date": "2013-03-04",
- "abstract": "Congenital central hypoventilation syndrome (CCHS) is an uncommon genetic disorder that is characterized by alveolar hypoventilation and autonomic dysregulation. More than 90% of the patients are heterozygous for polyalanine repeat expansion mutations in the paired-like homeobox 2b (PHOX2B) gene. The normal genotype has a 20-polyalanine sequence whereas expanded alleles are usually 25-33. Heterozygous 24-polyalanine repeat expansion mutation in the PHOX2B gene has rarely been reported. We report three consecutive generations harboring heterozygous 24-polyalanine repeats in the PHOX2B gene with manifestations ranging from apparently asymptomatic to alveolar hypoventilation and apnea requiring mechanical ventilation. The 3-year-old proband developed cor pulmonale and central hypoventilation following an upper respiratory tract infection. Our findings add to the accumulating evidence that the 24-polyalanine repeat in the PHOX2B is a disease-causing mutation. In addition, a high index of suspicion and careful monitoring after anesthesia, sedation, or respiratory illnesses should be exercised when evaluating asymptomatic family members with this genotype.",
+ "publisher": "Cerebellum (London, England)",
+ "issn": "1473-4230",
+ "date": "2024-12-16",
+ "abstract": "Clinically-relevant variants in the STUB1 gene have been associated with an autosomal dominant spinocerebellar ataxia 48 (SCA48), a recently described inherited neurodegenerative condition that is characterised by cognitive and psychiatric changes. To describe the clinical phenotype and genetic findings of three new Australian probands with STUB1 to expand the current understanding of the spectrum of clinical presentation and natural history of SCA48. Clinical and genetic review of patients diagnosed with SCA48 ataxia drawn from our centres. The third case was derived from a collaborating centre (Royal Brisbane Hospital). We identified three unrelated SCA48 patients with heterozygous pathogenic STUB1 variants. All presented with slowly progressive cerebellar ataxia with tremor and additional findings of dysarthria, parkinsonism, hypertonia, cognitive and psychiatric symptoms. Age of onset varied from 34 to 65 years of age. Brain MRI showed significant diffuse cerebellar atrophy, affecting the vermis and cerebellar hemispheres. We identified two novel pathogenic variants of STUB1 gene, and one previously reported pathogenic variant. Genetic testing for intermediate expansions of TBP (SCA17) identified TBP repeats within the normal range of 25-40 in all 3 probands. Our case series expands the clinical spectrum of SCA48. We highlight the importance of tremor as part of the clinical phenotype including upper limb rest tremor and Parkinsonian signs. Our cases lacked pathological TBP expansions and provide additional evidence that STUB1 (SCA48) can manifest as a monogenic disease.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23460419"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39680235"
},
{
- "id": "pmid:22829249",
+ "id": "pmid:39125760",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/22829249",
- "title": "Congenital central hypoventilation syndrome with PHOX2B gene mutation: are we missing the diagnosis?",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/39125760",
+ "title": "The New Face of Dynamic Mutation-The CAA [CAG]n CAA CAG Motif as a Mutable Unit in the",
"type": "article-journal",
- "doi": "10.1007/s12098-012-0837-2",
+ "doi": "10.3390/ijms25158190",
"authors": [
- ["Nilay", "Nirupam"],
- ["Rajni", "Sharma"],
- ["Viswas", "Chhapola"],
- ["Sandeep Kumar", "Kanwal"],
- ["Elizabeth M", "Berry-Kravis"],
- ["Virendra", "Kumar"]
+ ["Dorota", "Hoffman-Zacharska"],
+ ["Anna", "Sulek"]
],
- "publisher": "Indian journal of pediatrics",
- "issn": "0973-7693",
- "date": "2012-07-25",
- "abstract": "Congenital Central Hypoventilation Syndrome is a rare disorder of autonomic and central nervous system dysfunction with impaired control of breathing. The authors report a 37- d-old girl infant with recurrent apnea requiring repeated mechanical ventilation with no evidence of neuromuscular, cardiac or lung disease. A mutation analysis of PHOX2B gene revealed 25 polyalanine repeat expansion mutation on chromosome 4p12. This article aims at raising awareness among pediatricians about molecular basis and availability of confirmatory genetic testing for diagnosis and to help with prognosis in this disorder.",
+ "publisher": "International journal of molecular sciences",
+ "issn": "1422-0067",
+ "date": "2024-07-26",
+ "abstract": "Since 1991, several genetic disorders caused by unstable trinucleotide repeats (TNRs) have been identified, collectively referred to as triplet repeat diseases (TREDs). They share a common mutation mechanism: the expansion of repeats (dynamic mutations) due to the propensity of repeated sequences to form unusual DNA structures during replication. TREDs are characterized as neurodegenerative diseases or complex syndromes with significant neurological components. Spinocerebellar ataxia type 17 (SCA17) falls into the former category and is caused by the expansion of mixed CAA/CAG repeats in the",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22829249"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39125760"
},
{
- "id": "pmid:22821709",
+ "id": "pmid:37632648",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/22821709",
- "title": "Germline mosaicism of PHOX2B mutation accounts for familial recurrence of congenital central hypoventilation syndrome (CCHS).",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/37632648",
+ "title": "A DLB patient with complicated CAA interruptions and intermediate alleles of 43 CAG/CAA repeats in TBP.",
"type": "article-journal",
- "doi": "10.1002/ajmg.a.35499",
+ "doi": "10.1007/s13760-023-02351-6",
"authors": [
- ["Casey M", "Rand"],
- ["Min", "Yu"],
- ["Lawrence J", "Jennings"],
- ["Kelvin", "Panesar"],
- ["Elizabeth M", "Berry-Kravis"],
- ["Lili", "Zhou"],
- ["Debra E", "Weese-Mayer"]
+ ["Zhiru", "Lin"],
+ ["Jiaxiang", "Li"],
+ ["Wei", "Luo"]
],
- "publisher": "American journal of medical genetics. Part A",
- "issn": "1552-4833",
- "date": "2012-07-20",
- "abstract": "Congenital central hypoventilation syndrome (CCHS), a rare disorder characterized by alveolar hypoventilation and autonomic dysregulation, is caused by mutations in the PHOX2B gene. Most mutations occur de novo, but recent evidence suggests that up to 25% are inherited from asymptomatic parents with somatic mosaicism for these mutations. However, to date, germline mosaicism has not been reported. This report describes a family with recurrence of PHOX2B mutation-confirmed CCHS due to germline mosaicism. The first occurrence was a baby girl, noted on day 2 of life to have multiple episodes of apnea, bradycardia, and cyanosis while breathing room air. PHOX2B gene testing confirmed the diagnosis of CCHS with a heterozygous polyalanine repeat expansion mutation (PARM); genotype 20/27 (normal 20/20). Both parents tested negative for this mutation using fragment analysis (limit of detection<1%). Upon subsequent pregnancy [paternity confirmed using short tandem repeat (STR) analysis], amniocentesis testing identified the PHOX2B 20/27 genotype, confirmed with repeat testing. Elective abortion was performed at 21.5 weeks gestation. Testing of abortus tissue confirmed amniocentesis testing. The PHOX2B 20/27 expansion was not observed in a paternal sperm sample. This case represents the first reported family with recurrence of PHOX2B mutation-confirmed CCHS without detection of a parental carrier state or mosaicism, confirming the previously hypothesized possibility of germline mosaicism for PHOX2B mutations. This is an important finding for genetic counseling of CCHS families, suggesting that even if somatic mosaicism is not detected in parental samples, there is still reason for careful genetic counseling and consideration of prenatal testing during subsequent pregnancies.",
+ "publisher": "Acta neurologica Belgica",
+ "issn": "2240-2993",
+ "date": "2023-08-26",
+ "abstract": "",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22821709"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37632648"
},
{
- "id": "pmid:22437207",
+ "id": "pmid:36476347",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/22437207",
- "title": "Inheritance of polyalanine expansion mutation of PHOX2B in congenital central hypoventilation syndrome.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/36476347",
+ "title": "Spinocerebellar ataxia type 17-digenic TBP/STUB1 disease: neuropathologic features of an autopsied patient.",
"type": "article-journal",
- "doi": "10.1038/jhg.2012.27",
+ "doi": "10.1186/s40478-022-01486-6",
"authors": [
- ["Toru", "Meguro"],
- ["Yuki", "Yoshida"],
- ["Makiko", "Hayashi"],
- ["Kentaro", "Toyota"],
- ["Tesshu", "Otagiri"],
- ["Narutaka", "Mochizuki"],
- ["Yumiko", "Kishikawa"],
- ["Ayako", "Sasaki"],
- ["Kiyoshi", "Hayasaka"]
+ ["Rie", "Saito"],
+ ["Yui", "Tada"],
+ ["Daisuke", "Oikawa"],
+ ["Yusuke", "Sato"],
+ ["Makiko", "Seto"],
+ ["Akira", "Satoh"],
+ ["Kodai", "Kume"],
+ ["Nozomi", "Ueki"],
+ ["Masahiro", "Nakashima"],
+ ["Shintaro", "Hayashi"],
+ ["Yasuko", "Toyoshima"],
+ ["Fuminori", "Tokunaga"],
+ ["Hideshi", "Kawakami"],
+ ["Akiyoshi", "Kakita"]
],
- "publisher": "Journal of human genetics",
- "issn": "1435-232X",
- "date": "2012-03-22",
- "abstract": "Congenital central hypoventilation syndrome (CCHS; MIM 209880) is caused mostly by dominant alanine expansion (most prevalent is 7-alanine expansion) mutations in PHOX2B. More than 90% of the alanine expansion mutations had been considered to be de novo due to unequal crossover during gametogenesis. However, a recent report stated that 25% of patients inherited the alanine-expanded allele from their parents with somatic mosaicism or constitutive mutation. We studied inheritance in 45 unrelated families, and found that one patient (2%) inherited 5-alanine expansion mutation from a parent with late-onset central hypoventilation syndrome and nine patients (20%) inherited 5- to 7-alanine expansion mutation from apparently asymptomatic parents with somatic mosaicism. Analysis using a sensitive method would be recommended to all parents of CCHS proband due to high incidence of somatic mosaicism. The absence of an alanine-contracted allele (expected counterpart allele in unequal crossover) and the highest prevalence of 6-alanine expansion mutation in somatic mosaicism suggest that the somatic mosaicism is likely caused by a mechanism other than an unequal crossover, such as a replication mechanism.",
+ "publisher": "Acta neuropathologica communications",
+ "issn": "2051-5960",
+ "date": "2022-12-07",
+ "abstract": "Spinocerebellar ataxia (SCA) type 17-digenic TBP/STUB1 disease (SCA17-DI) has been recently segregated from SCA17, caused by digenic inheritance of two gene mutations - intermediate polyglutamine-encoding CAG/CAA repeat expansions (polyQ) in TBP (TBP",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22437207"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36476347"
},
{
- "id": "pmid:20236122",
+ "id": "pmid:36422518",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/20236122",
- "title": "Congenital central hypoventilation syndrome: genotype-phenotype correlation in parents of affected children carrying a PHOX2B expansion mutation.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/36422518",
+ "title": "Intermediate repeat expansions of TBP and STUB1: Genetic modifier or pure digenic inheritance in spinocerebellar ataxias?",
"type": "article-journal",
- "doi": "10.1111/j.1399-0004.2010.01383.x",
+ "doi": "10.1016/j.gim.2022.10.009",
"authors": [
- ["S", "Parodi"],
- ["C", "Vollono"],
- ["M P", "Baglietto"],
- ["M", "Balestri"],
- ["M", "Di Duca"],
- ["P A", "Landri"],
- ["I", "Ceccherini"],
- ["G", "Ottonello"],
- ["M R", "Cilio"]
+ ["Mathieu", "Barbier"],
+ ["Claire-Sophie", "Davoine"],
+ ["Emilien", "Petit"],
+ ["Maximilien", "Porch\u00e9"],
+ ["L\u00e9na", "Guillot-Noel"],
+ ["Sabrina", "Sayah"],
+ ["Anne-Laure", "Fauret"],
+ ["Jean-Philippe", "Neau"],
+ ["Lucie", "Guyant-Mar\u00e9chal"],
+ ["Didier", "Deffond"],
+ ["Christine", "Tranchant"],
+ ["Cyril", "Goizet"],
+ ["Giulia", "Coarelli"],
+ ["Anna", "Castrioto"],
+ ["Stephan", "Klebe"],
+ ["Claire", "Ewenczyk"],
+ ["Anna", "Heinzmann"],
+ ["Perrine", "Charles"],
+ ["Maya", "Tchikviladz\u00e9"],
+ ["Christine", "Van Broeckhoven"],
+ ["Alexis", "Brice"],
+ ["Alexandra", "Durr"]
],
- "publisher": "Clinical genetics",
- "issn": "1399-0004",
- "date": "2010-02-11",
- "abstract": "Congenital Central Hypoventilation Syndrome (CCHS) is a rare genetic disorder. Although most CCHS associated PHOX2B mutations occur de novo, about 10% of the cases are inherited from apparently asymptomatic parents, thus confirming variable expressivity and incomplete penetrance of PHOX2B mutations. Three asymptomatic parents of children affected with CCHS, and found to carry the same PHOX2B expansion mutations as their siblings, were studied by overnight polysomnography and somatic mosaicism analysis. In one case, significant sleep breathing control anomalies were detected, while the other two resulted in normal. In tissue-specific allele studies, mosaicism with a comparatively low mutant allele proportion was showed in the two unaffected adult carriers. Accurate polysomnography and assessment of the degree of somatic mosaicism should be conducted in asymptomatic carriers of PHOX2B mutations, as they may unmask subclinical but significant anomalies.",
+ "publisher": "Genetics in medicine : official journal of the American College of Medical Genetics",
+ "issn": "1530-0366",
+ "date": "2022-11-23",
+ "abstract": "CAG/CAA repeat expansions in TBP",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20236122"
-},
-{
- "id": "pmid:19881470",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/19881470",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:19881470']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36422518"
},
{
- "id": "pmid:19608868",
+ "id": "pmid:35482253",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/19608868",
- "title": "MYCN promotes the expansion of Phox2B-positive neuronal progenitors to drive neuroblastoma development.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/35482253",
+ "title": "Calpains as novel players in the molecular pathogenesis of spinocerebellar ataxia type 17.",
"type": "article-journal",
- "doi": "10.2353/ajpath.2009.090019",
+ "doi": "10.1007/s00018-022-04274-6",
"authors": [
- ["Goleeta", "Alam"],
- ["Hongjuan", "Cui"],
- ["Huilin", "Shi"],
- ["Liqun", "Yang"],
- ["Jane", "Ding"],
- ["Ling", "Mao"],
- ["William A", "Maltese"],
- ["Han-Fei", "Ding"]
+ ["Jonasz Jeremiasz", "Weber"],
+ ["Stefanie Cari", "Anger"],
+ ["Priscila", "Pereira Sena"],
+ ["Rana Dilara", "Incebacak Eltemur"],
+ ["Chrisovalantou", "Huridou"],
+ ["Florian", "Fath"],
+ ["Caspar", "Gross"],
+ ["Nicolas", "Casadei"],
+ ["Olaf", "Riess"],
+ ["Huu Phuc", "Nguyen"]
],
- "publisher": "The American journal of pathology",
- "issn": "1525-2191",
- "date": "2009-07-16",
- "abstract": "Amplification of the oncogene MYCN is a tumorigenic event in the development of a subset of neuroblastomas that commonly consist of undifferentiated or poorly differentiated neuroblasts with unfavorable clinical outcome. The cellular origin of these neuroblasts is unknown. Additionally, the cellular functions and target cells of MYCN in neuroblastoma development remain undefined. Here we examine the cell types that drive neuroblastoma development in TH-MYCN transgenic mice, an animal model of the human disease. Neuroblastoma development in these mice begins with hyperplastic lesions in early postnatal sympathetic ganglia. We show that both hyperplasia and primary tumors are composed predominantly of highly proliferative Phox2B(+) neuronal progenitors. MYCN induces the expansion of these progenitors by both promoting their proliferation and preventing their differentiation. We further identify a minor population of undifferentiated nestin(+) cells in both hyperplastic lesions and primary tumors that may serve as precursors of Phox2B(+) neuronal progenitors. These findings establish the identity of neuroblasts that characterize the tumor phenotype and suggest a cellular pathway by which MYCN can promote neuroblastoma development.",
+ "publisher": "Cellular and molecular life sciences : CMLS",
+ "issn": "1420-9071",
+ "date": "2022-04-28",
+ "abstract": "Spinocerebellar ataxia type 17 (SCA17) is a neurodegenerative disease caused by a polyglutamine-encoding trinucleotide repeat expansion in the gene of transcription factor TATA box-binding protein (TBP). While its underlying pathomechanism is elusive, polyglutamine-expanded TBP fragments of unknown origin mediate the mutant protein's toxicity. Calcium-dependent calpain proteases are protagonists in neurodegenerative disorders. Here, we demonstrate that calpains cleave TBP, and emerging C-terminal fragments mislocalize to the cytoplasm. SCA17 cell and rat models exhibited calpain overactivation, leading to excessive fragmentation and depletion of neuronal proteins in vivo. Transcriptome analysis of SCA17 cells revealed synaptogenesis and calcium signaling perturbations, indicating the potential cause of elevated calpain activity. Pharmacological or genetic calpain inhibition reduced TBP cleavage and aggregation, consequently improving cell viability. Our work underlines the general significance of calpains and their activating pathways in neurodegenerative disorders and presents these proteases as novel players in the molecular pathogenesis of SCA17.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19608868"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35482253"
},
{
- "id": "pmid:17909190",
+ "id": "pmid:34906452",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/17909190",
- "title": "Central hypoventilation with PHOX2B expansion mutation presenting in adulthood.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/34906452",
+ "title": "Digenic inheritance of STUB1 variants and TBP polyglutamine expansions explains the incomplete penetrance of SCA17 and SCA48.",
"type": "article-journal",
- "doi": "10.1136/thx.2006.068908",
+ "doi": "10.1016/j.gim.2021.08.003",
"authors": [
- ["S", "Barratt"],
- ["A H", "Kendrick"],
- ["F", "Buchanan"],
- ["A T", "Whittle"]
+ ["Stefania", "Magri"],
+ ["Lorenzo", "Nanetti"],
+ ["Cinzia", "Gellera"],
+ ["Elisa", "Sarto"],
+ ["Elena", "Rizzo"],
+ ["Alessia", "Mongelli"],
+ ["Benedetta", "Ricci"],
+ ["Roberto", "Fancellu"],
+ ["Luisa", "Sambati"],
+ ["Pietro", "Cortelli"],
+ ["Alfredo", "Brusco"],
+ ["Maria Grazia", "Bruzzone"],
+ ["Caterina", "Mariotti"],
+ ["Daniela", "Di Bella"],
+ ["Franco", "Taroni"]
],
- "publisher": "Thorax",
- "issn": "0040-6376",
- "date": "2007-10-01",
- "abstract": "Congenital central hypoventilation syndrome most commonly presents in neonates with sleep related hypoventilation; late onset cases have occurred up to the age of 10 years. It is associated with mutations in the PHOX2B gene, encoding a transcription factor involved in autonomic nervous system development. The case history is described of an adult who presented with chronic respiratory failure due to PHOX2B mutation-associated central hypoventilation and an impaired response to hypercapnia.",
+ "publisher": "Genetics in medicine : official journal of the American College of Medical Genetics",
+ "issn": "1530-0366",
+ "date": "2021-11-30",
+ "abstract": "This study aimed to unravel the genetic factors underlying missing heritability in spinocerebellar ataxia type 17 (SCA17) caused by polyglutamine-encoding CAG/CAA repeat expansions in the TBP gene. Alleles with >49 CAG/CAA repeats are fully penetrant. Most patients, however, carry intermediate TBP",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17909190"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34906452"
},
{
- "id": "pmid:17045833",
+ "id": "pmid:31919387",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/17045833",
- "title": "Geldanamycin promotes nuclear localisation and clearance of PHOX2B misfolded proteins containing polyalanine expansions.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/31919387",
+ "title": "Interferon mediated neuroinflammation in polyglutamine disease is not caused by RNA toxicity.",
"type": "article-journal",
- "doi": "10.1016/j.biocel.2006.08.014",
+ "doi": "10.1038/s41419-019-2193-x",
"authors": [
- ["Tiziana", "Bachetti"],
- ["Paola", "Bocca"],
- ["Silvia", "Borghini"],
- ["Ivana", "Matera"],
- ["Ignazia", "Prigione"],
- ["Roberto", "Ravazzolo"],
- ["Isabella", "Ceccherini"]
+ ["Aksheev", "Bhambri"],
+ ["Akeeth", "Pinto"],
+ ["Beena", "Pillai"]
],
- "publisher": "The international journal of biochemistry & cell biology",
- "issn": "1357-2725",
- "date": "2006-09-14",
- "abstract": "Polyalanine expansions in the PHOX2B gene have been detected in the vast majority of patients affected with congenital central hypoventilation syndrome, a neurocristopathy characterized by absence of adequate control of breathing, especially during sleep, with decreased sensitivity to hypoxia and hypercapnia. The correlation between length of the alanine expanded tracts and severity of congenital central hypoventilation syndrome respiratory phenotype has been confirmed by length-dependent cytoplasmic PHOX2B retention with formation of aggregates. To deepen into the molecular mechanisms mediating the effects of PHOX2B polyalanine expansions, we have set up experiments aimed at assessing the fate of cells characterized by PHOX2B polyalanine aggregates. In particular, we have observed that activation of the heat shock response by the drug geldanamycin is efficient both in preventing formation and in inducing clearance of PHOX2B pre-formed polyalanine aggregates in COS-7 cells expressing PHOX2B-GFP fused proteins, and ultimately also in rescuing the PHOX2B ability to transactivate the Dopamine-beta-Hydroxilase promoter. In addition, we have demonstrated elimination of PHOX2B mutant proteins by the proteasome and autophagy, two cellular mechanisms already been involved in the clearance of proteins containing expanded polyglutamine and polyalanine tracts. Moreover, our data suggest that geldanamycin effects on PHOX2B aggregates may be also mediated by the proteasome pathway. Finally, analysis of cellular toxicity due to polyalanine aggregates has confirmed the occurrence of cell apoptosis consequent to expression of PHOX2B carrying the longest expanded alanine tract and shown that geldanamycin can delay cell progression toward the most advanced apoptotic stages.",
+ "publisher": "Cell death & disease",
+ "issn": "2041-4889",
+ "date": "2020-01-02",
+ "abstract": "Polyglutamine diseases are neurodegenerative diseases that occur due to the expansion of CAG repeat regions in coding sequences of genes. Previously, we have shown the formation of large protein aggregates along with activation of the interferon pathway leading to apoptosis in a cellular model of SCA17. Here, we corroborate our previous results in a tetracycline-inducible model of SCA17. Interferon gamma and lambda were upregulated in 59Q-TBP expressing cells as compared to 16Q-TBP expressing cells. Besides interferon-stimulated genes, the SCA17 model and Huntington's mice brain samples showed upregulation of RNA sensors. However, in this improved model interferon pathway activation and apoptosis preceded the formation of large polyglutamine aggregates, suggesting a role for CAG repeat RNA or soluble protein aggregates. A polyglutamine minus mutant of TBP, expressing polyCAG mRNA, was created by site directed mutagenesis of 10 potential start codons. Neither this long CAG embedded mRNA nor short polyCAG RNA could induce interferon pathway genes or cause apoptosis. polyQ-TBP induced the expression of canonical RNA sensors but the downstream transcription factor, IRF3, showed a muted response. We found that expanded CAG repeat RNA is not sufficient to account for the neuronal apoptosis. Neuronal cells sense expanded CAG repeats embedded in messenger RNAs of protein-coding genes. However, polyglutamine containing protein is responsible for the interferon-mediated neuroinflammation and cell death seen in polyglutamine disease. Thus, we delineate the inflammatory role of CAG repeats in the mRNA from the resulting polyglutamine tract in the protein. Embedded in messenger RNAs of protein-coding regions, the cell senses CAG repeat expansion and induces the expression of RNA sensors and interferon-stimulated genes.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17045833"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31919387"
},
{
- "id": "pmid:16888290",
+ "id": "pmid:30532692",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/16888290",
- "title": "Congenital central hypoventilation syndrome: PHOX2B mutations and phenotype.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30532692",
+ "title": "Complexity of the Genetics and Clinical Presentation of Spinocerebellar Ataxia 17.",
"type": "article-journal",
- "doi": "10.1164/rccm.200602-305oc",
+ "doi": "10.3389/fncel.2018.00429",
"authors": [
- ["Elizabeth M", "Berry-Kravis"],
- ["Lili", "Zhou"],
- ["Casey M", "Rand"],
- ["Debra E", "Weese-Mayer"]
+ ["Suran", "Nethisinghe"],
+ ["Wei N", "Lim"],
+ ["Heather", "Ging"],
+ ["Anna", "Zeitlberger"],
+ ["Rosella", "Abeti"],
+ ["Sally", "Pemble"],
+ ["Mary G", "Sweeney"],
+ ["Robyn", "Labrum"],
+ ["Charisse", "Cervera"],
+ ["Henry", "Houlden"],
+ ["Elisabeth", "Rosser"],
+ ["Patricia", "Limousin"],
+ ["Angus", "Kennedy"],
+ ["Michael P", "Lunn"],
+ ["Kailash P", "Bhatia"],
+ ["Nicholas W", "Wood"],
+ ["John", "Hardy"],
+ ["James M", "Polke"],
+ ["Liana", "Veneziano"],
+ ["Alfredo", "Brusco"],
+ ["Mary B", "Davis"],
+ ["Paola", "Giunti"]
],
- "publisher": "American journal of respiratory and critical care medicine",
- "issn": "1073-449X",
- "date": "2006-08-03",
- "abstract": "Congenital central hypoventilation syndrome (CCHS), a unique disorder of respiratory control associated with Hirschsprung disease (HSCR) and tumors of neural crest origin, results from polyalanine repeat expansion mutations in the paired-like homeobox (PHOX)2B gene in more than 90% of cases, and alternative PHOX2B mutations in remaining cases.",
+ "publisher": "Frontiers in cellular neuroscience",
+ "issn": "1662-5102",
+ "date": "2018-11-23",
+ "abstract": "Spinocerebellar ataxia type 17 (SCA17) is a rare autosomal dominant neurodegenerative disease caused by a CAG repeat expansion in the TATA-box binding protein gene (",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16888290"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30532692"
},
{
- "id": "pmid:40488265",
+ "id": "pmid:27865706",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/40488265",
- "title": "Current understanding of skeletal muscle repeat expansion disorders.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27865706",
+ "title": "Age-related length variability of polymorphic CAG repeats.",
"type": "article-journal",
- "doi": "10.1097/wco.0000000000001394",
+ "doi": "10.1016/j.dnarep.2016.10.003",
"authors": [
- ["Manon", "Boivin"],
- ["Gianina", "Ravenscroft"]
+ ["Monica", "Sanchez-Contreras"],
+ ["Fernando", "Cardozo-Pelaez"]
],
- "publisher": "Current opinion in neurology",
- "issn": "1473-6551",
- "date": "2025-06-10",
- "abstract": "Here, we summarize the current knowledge about the genetics and proposed mechanisms of disease underlying skeletal muscle short tandem repeat (STR) expansion disorders.",
+ "publisher": "DNA repair",
+ "issn": "1568-7856",
+ "date": "2016-10-15",
+ "abstract": "Somatic instability of CAG repeats has been associated with the clinical progression of CAG repeat diseases. Aging and DNA repair processes influence the somatic stability of CAG repeat in disease and in mouse models. However, most of the studies have focused on genetically engineered transgenic repeats and little is known about the stability of naturally polymorphic CAG repeats. To study whether age and/or DNA repair activity have an effect on the somatic stability of CAG repeats, we analyzed variations of the length of naturally polymorphic CAG repeats in the striatum of young and aged WT and ogg1 KO mice. Some multiple and long polymorphic CAG repeats were observed to have variable length in the striatum of aged mice. Interestingly, a low level of repeat variability was detected in the CAG repeat located in tbp, the only mouse polymorphic CAG repeat that is associated with a trinucleotide disease in humans, in the striatum of aged mice and not in young mice. We propose that age may have an effect on the somatic stability of polymorphic CAG repeats and that such an effect depends on intrinsic CAG repeat characteristics.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40488265"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27865706"
},
{
- "id": "pmid:29029963",
+ "id": "pmid:27172828",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/29029963",
- "title": "Genetic risk factors in Finnish patients with Parkinson's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27172828",
+ "title": "Trinucleotide repeat expansion of TATA-binding protein gene associated with Parkinson's disease: A Thai multicenter study.",
"type": "article-journal",
- "doi": "10.1016/j.parkreldis.2017.09.021",
+ "doi": "10.1016/j.parkreldis.2016.05.008",
"authors": [
- ["Susanna", "Yl\u00f6nen"],
- ["Ari", "Siitonen"],
- ["Michael A", "Nalls"],
- ["Pauli", "Ylikotila"],
- ["Jaana", "Autere"],
- ["Johanna", "Eerola-Rautio"],
- ["Raphael", "Gibbs"],
- ["Mikko", "Hiltunen"],
- ["Pentti J", "Tienari"],
- ["Hilkka", "Soininen"],
- ["Andrew B", "Singleton"],
- ["Kari", "Majamaa"]
+ ["Lulin", "Choubtum"],
+ ["Pirada", "Witoonpanich"],
+ ["Kongkiat", "Kulkantrakorn"],
+ ["Suchat", "Hanchaiphiboolkul"],
+ ["Sunsanee", "Pongpakdee"],
+ ["Somsak", "Tiamkao"],
+ ["Teeratorn", "Pulkes"]
],
"publisher": "Parkinsonism & related disorders",
"issn": "1873-5126",
- "date": "2017-09-29",
- "abstract": "Variation contributing to the risk of Parkinson's disease (PD) has been identified in several genes and at several loci including GBA, SMPD1, LRRK2, POLG1, CHCHD10 and MAPT, but the frequencies of risk variants seem to vary according to ethnic background. Our aim was to analyze how variation in these genes contributes to PD in the Finnish population.",
+ "date": "2016-05-04",
+ "abstract": "Spinocerebellar ataxia type 17 (SCA17) is an inherited cerebellar degeneration associated with trinucleotide repeat expansions in the TATA-binding protein gene (TBP). Low-range expansions of TBP have recently been described in association with Parkinson's disease (PD). However, these low-range expansion alleles were also observed in healthy individuals. Prior distinct findings may result from reduced penetrance or age-dependent susceptibility, which may influence phenotypic expression.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29029963"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27172828"
},
{
- "id": "pmid:25767537",
+ "id": "pmid:26476771",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25767537",
- "title": "The POLG Polyglutamine Tract Variants in Iranian Patients with Multiple Sclerosis.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26476771",
+ "title": "Pathological repeat variation at the SCA17/TBP gene in south Indian patients.",
"type": "article-journal",
- "doi": "",
+ "doi": "10.1016/j.jns.2015.07.044",
"authors": [
- ["Mehri", "Khatami"],
- ["Mohammad Mehdi", "Heidari"],
- ["Reza", "Mansouri"],
- ["Fatemeh", "Mousavi"]
+ ["Waseem Gul", "Lone"],
+ ["Imran Ali", "Khan"],
+ ["Noor Ahmad", "Shaik"],
+ ["Angmuthu Kanikannan", "Meena"],
+ ["Kaipa Prabhakar", "Rao"],
+ ["Qurratulain", "Hasan"]
],
- "publisher": "Iranian journal of child neurology",
- "issn": "1735-4668",
- "date": "2015-01-01",
- "abstract": "Multiple Sclerosis (MS) is a common disease of the central nervous system. The interaction between inflammatory and neurodegenerative processes typically results in irregular neurological disturbances followed by progressive disability. Mitochondrial dysfunction has been implicated in neurodegenerative disorders. The DNA polymerase-gamma (POLG) gene, which encodes the catalytic subunit of enzyme responsible for directing mtDNA replication, contains a poly glutamine tract (poly-Q) in the N-terminal, encoded by a CAG sequence in exon 2.",
- "language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25767537"
-},
-{
- "id": "pmid:23493802",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/23493802",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:23493802']' timed out after 3 seconds"
+ "publisher": "Journal of the neurological sciences",
+ "issn": "1878-5883",
+ "date": "2015-08-21",
+ "abstract": "Despite the intense debate around the repeat instability reported on the large group of neurological disorders caused by trinucleotide repeat expansions, little is known about the mutation process underlying alleles in the normal range, diseases range, large normal alleles (LNAs). In this study, we assessed the CAG repeats at SCA17 in 188 clinical SCA patients and 100 individuals without any neurological signs. This highly polymorphic population displayed high variability in the CAG repeats and ranged from 19-38 CAG repeats in patients with mode of 20 and 19-32 CAG repeats in controls with mode of 24. The triplet repeat expansion was not detected in any of the 188 patients, as per the reference pathogenic range (>43 repeats); however, 2.7% of the patients had >33 CAG repeats with a clinical phenotype close to what is expected of SCA 17 patients. The findings of this study implicate a more sophisticated interpretation of SCA17 gene and raise the question about the diagnostic thresh hold between normal and expanded repeats in our population.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26476771"
},
{
- "id": "pmid:20803511",
+ "id": "pmid:26387956",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/20803511",
- "title": "POLG, but not PEO1, is a frequent cause of cerebellar ataxia in Central Europe.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26387956",
+ "title": "Large Polyglutamine Repeats Cause Muscle Degeneration in SCA17 Mice.",
"type": "article-journal",
- "doi": "10.1002/mds.23286",
+ "doi": "10.1016/j.celrep.2015.08.060",
"authors": [
- ["Julia", "Schicks"],
- ["Matthis", "Synofzik"],
- ["Claudia", "Schulte"],
- ["Ludger", "Sch\u00f6ls"]
+ ["Shanshan", "Huang"],
+ ["Su", "Yang"],
+ ["Jifeng", "Guo"],
+ ["Sen", "Yan"],
+ ["Marta A", "Gaertig"],
+ ["Shihua", "Li"],
+ ["Xiao-Jiang", "Li"]
],
- "publisher": "Movement disorders : official journal of the Movement Disorder Society",
- "issn": "1531-8257",
- "date": "2010-11-15",
- "abstract": "Nuclear genes, in particular mitochondrial polymerase gamma (POLG) and PEO1, have been increasingly recognized to cause mitochondrial diseases. Both genes assume a complementary role as part of the mitochondrial DNA (mtDNA) replication fork and, accordingly, seem to present with largely overlapping phenotypical spectra. We assessed the frequency and phenotypic spectrum of PEO1 compared to POLG mutations in a cohort of 80 patients with cerebellar ataxia for which common repeat expansion diseases had been excluded. Patients were selected to present additional features previously described for PEO1 mutations, namely early age of onset, progressive external ophthalmoplegia (PEO), or epilepsy. Whereas PEO1 mutations were not found in our cohort, POLG frequently caused ataxia with PEO (47%), psychiatric comorbidities (20%) and, more rarely, with epilepsy (14%). Thus, PEO1 is rare in Central Europe even in those patients displaying characteristic phenotypic features. In contrast, POLG is rather common in Central European ataxia patients. It should be particularly considered in ataxia patients with PEO, psychiatric comorbidities, and/or sensory neuropathy, even if characteristic mitochondrial extra-CNS features are absent.",
+ "publisher": "Cell reports",
+ "issn": "2211-1247",
+ "date": "2015-09-17",
+ "abstract": "In polyglutamine (polyQ) diseases, large polyQ repeats cause juvenile cases with different symptoms than those of adult-onset patients, who carry smaller expanded polyQ repeats. The mechanisms behind the differential pathology mediated by different polyQ repeat lengths remain unknown. By studying knockin mouse models of spinal cerebellar ataxia-17 (SCA17), we found that a large polyQ (105 glutamines) in the TATA-box-binding protein (TBP) preferentially causes muscle degeneration and reduces the expression of muscle-specific genes. Direct expression of TBP with different polyQ repeats in mouse muscle revealed that muscle degeneration is mediated only by the large polyQ repeats. Different polyQ repeats differentially alter TBP's interaction with neuronal and muscle-specific transcription factors. As a result, the large polyQ repeat decreases the association of MyoD with TBP and DNA promoters. Our findings suggest that specific alterations in protein interactions by large polyQ repeats may account for the unique pathology in juvenile polyQ diseases.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20803511"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26387956"
},
{
- "id": "pmid:12036482",
+ "id": "pmid:25672822",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/12036482",
- "title": "Lack of correlation between length variation in the DNA polymerase gamma gene CAG repeat and lactic acidosis or neuropathy during antiretroviral treatment.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25672822",
+ "title": "Trehalose attenuates the gait ataxia and gliosis of spinocerebellar ataxia type 17 mice.",
"type": "article-journal",
- "doi": "10.1089/088922202753747879",
+ "doi": "10.1007/s11064-015-1530-4",
"authors": [
- ["Xianghong", "Chen"],
- ["Jaap", "Goudsmit"],
- ["Antoinette C", "van der Kuyl"]
+ ["Zhi-Zhong", "Chen"],
+ ["Chien-Ming", "Wang"],
+ ["Guan-Chiun", "Lee"],
+ ["Ho-Chiang", "Hsu"],
+ ["Tzu-Ling", "Wu"],
+ ["Chia-Wei", "Lin"],
+ ["Chih-Kang", "Ma"],
+ ["Guey-Jen", "Lee-Chen"],
+ ["Hei-Jen", "Huang"],
+ ["Hsiu Mei", "Hsieh-Li"]
],
- "publisher": "AIDS research and human retroviruses",
- "issn": "0889-2229",
- "date": "2002-05-20",
- "abstract": "Antiretroviral therapy, although successful in reducing HIV load and accordingly decreasing the incidence of HIV infection-related symptoms, has its drawbacks in the form of severe side effects. Recognized drug-related side effects are, for example, nausea, fatigue, lactic acidosis, neuropathy, lipodystrophy, and myopathy. Because not all patients experience these side effects, genetic factors could be involved. It is believed that the main toxicity of nucleoside analog drugs is due to a decrease in mitochondrial function, possibly by inhibition of mitochondrial DNA (mtDNA) replication. mtDNA is replicated by a multienzyme complex, the main component of which is the nuclear-encoded DNA polymerase gamma. Presently, the only known variation in the DNA polymerase gamma gene is variation in the number of CAG repeats in the second exon. To investigate whether CAG repeat expansion or mutations in the DNA polymerase gamma (POLG) gene could predispose to peripheral neuropathy or lactic acidosis, we have sequenced part of the second exon of the DNA polymerase gamma gene, containing the CAG repeat, of 59 drug-treated HIV-infected patients, 11 of whom experienced drug-induced neuropathy, and 3 of whom died from lactic acidosis. No correlation was found between numbers of CAG repeats and any of the symptoms. The coding regions of the POLG gene from the three lactic acidosis patients were then completely sequenced, but no mutations were found. In addition, no variation was detected in exons 3, 8, and 19 of seven neuropathy patients and three control subjects without symptoms. These exons were the only sites of amino acid changes between human and chimpanzee POLG genes, and were chosen as targets of tolerated variation.",
+ "publisher": "Neurochemical research",
+ "issn": "1573-6903",
+ "date": "2015-02-12",
+ "abstract": "Spinocerebellar ataxia type 17 (SCA17) is caused by CAG/CAA repeat expansion on the gene encoding a general transcription factor, TATA-box-binding protein (TBP). The CAG repeat expansion leads to the reduced solubility of polyglutamine TBP and induces aggregate formation. The TBP aggregation, mostly present in the cell nuclei, is distinct from that in most other neurodegenerative diseases, in which the aggregation is formed in cytosol or extracellular compartments. Trehalose is a disaccharide issued by the Food and Drug Administration with a Generally Recognized As Safe status. Lines of evidence suggest trehalose could prevent protein aggregate formation in several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. In this study, we evaluated the therapeutic potential of trehalose on SCA17 using cerebellar primary and organotypic culture systems and a mouse model. Our results showed that TBP nuclear aggregation was significantly decreased in both the primary and slice cultures. Trehalose (4 %) was further supplied in the drinking water of SCA17 transgenic mice. We found both the gait behavior in the footprint analysis and motor coordination in the rotarod task were significantly improved in the trehalose-treated SCA17 mice. The cerebellar weight was increased and the astrocyte gliosis was reduced in SCA17 mice after trehalose treatment. These data suggest that trehalose could be a potential nontoxic treatment for SCA17.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12036482"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25672822"
},
{
- "id": "pmid:38798069",
+ "id": "pmid:23665119",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/38798069",
- "title": "Role of B\u03b21 overexpression in the pathogenesis of SCA12.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23665119",
+ "title": "Automated home cage assessment shows behavioral changes in a transgenic mouse model of spinocerebellar ataxia type 17.",
"type": "article-journal",
- "doi": "10.1002/mds.29839",
+ "doi": "10.1016/j.bbr.2013.04.042",
"authors": [
- ["Chengqian", "Zhou"],
- ["Fan", "Tang"],
- ["Tao", "Dong"],
- ["Hans B", "Liu"],
- ["Leon", "Deng"],
- ["Russell L", "Margolis"],
- ["Pan P", "Li"]
+ ["Esteban", "Portal"],
+ ["Olaf", "Riess"],
+ ["Huu Phuc", "Nguyen"]
],
- "publisher": "Movement disorders : official journal of the Movement Disorder Society",
- "issn": "1531-8257",
- "date": "2024-05-26",
- "abstract": "Spinocerebellar ataxia type 12 (SCA12) is a neurodegenerative disease caused by a CAG/CTG repeat expansion at the PPP2R2B locus.",
+ "publisher": "Behavioural brain research",
+ "issn": "1872-7549",
+ "date": "2013-05-07",
+ "abstract": "Spinocerebellar Ataxia type 17 (SCA17) is an autosomal dominantly inherited, neurodegenerative disease characterized by ataxia, involuntary movements, and dementia. A novel SCA17 mouse model having a 71 polyglutamine repeat expansion in the TATA-binding protein (TBP) has shown age related motor deficit using a classic motor test, yet concomitant weight increase might be a confounding factor for this measurement. In this study we used an automated home cage system to test several motor readouts for this same model to confirm pathological behavior results and evaluate benefits of automated home cage in behavior phenotyping. Our results confirm motor deficits in the Tbp/Q71 mice and present previously unrecognized behavioral characteristics obtained from the automated home cage, indicating its use for high-throughput screening and testing, e.g. of therapeutic compounds.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38798069"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23665119"
},
{
- "id": "pmid:38711441",
+ "id": "pmid:23475385",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/38711441",
- "title": "Molecular clues unveiling spinocerebellar ataxia type-12 pathogenesis.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23475385",
+ "title": "From normal gait to loss of ambulation in 6 months: a novel presentation of SCA17.",
"type": "article-journal",
- "doi": "10.1016/j.isci.2024.109768",
+ "doi": "10.1007/s12311-013-0466-y",
"authors": [
- ["Manish", "Kumar"],
- ["Shweta", "Sahni"],
- ["Vivekanand", "A"],
- ["Deepak", "Kumar"],
- ["Neetu", "Kushwah"],
- ["Divya", "Goel"],
- ["Himanshi", "Kapoor"],
- ["Achal K", "Srivastava"],
- ["Mohammed", "Faruq"]
+ ["R", "Mehanna"],
+ ["I", "Itin"]
],
- "publisher": "iScience",
- "issn": "2589-0042",
- "date": "2024-04-18",
- "abstract": "Spinocerebellar Ataxia type-12 (SCA12) is a neurodegenerative disease caused by tandem CAG repeat expansion in the 5'-UTR/non-coding region of",
+ "publisher": "Cerebellum (London, England)",
+ "issn": "1473-4230",
+ "date": "2013-08-01",
+ "abstract": "Spinocerebellar ataxias are a group of rare and heterogeneous autosomal dominant disorders characterized by progressive ataxia and other features. Spinocerebellar ataxia 17 (SCA17) is one of the 32 subtypes described to date and is secondary to CAG/CAA repeat expansion in the gene coding for the TATA-box binding protein (TBP). SCA17 is clinically heterogeneous and typically presents with slowly evolving ataxia, dysarthria, dementia, depression, and other movement disorders such as chorea. More than 41 CAG/CAA repeats are considered diagnostic of SCA17, with more than 49 being associated with full penetrance. We report one patient presenting with isolated rapidly evolving ataxia who was found to have 44 CAG/CAA repeats in the TBP gene. This suggests that, while SCA17 typically slowly progresses over years, its repertoire of presentations should be expanded to include rapidly progressive isolated ataxia resembling paraneoplastic disorders or prion disease.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38711441"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23475385"
},
{
- "id": "pmid:30130680",
+ "id": "pmid:21562248",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/30130680",
- "title": "Generation of three spinocerebellar ataxia type-12 patients derived induced pluripotent stem cell lines (IGIBi002-A, IGIBi003-A and IGIBi004-A).",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21562248",
+ "title": "Evaluating the prevalence of polyglutamine repeat expansions in amyotrophic lateral sclerosis.",
"type": "article-journal",
- "doi": "10.1016/j.scr.2018.08.008",
+ "doi": "10.1212/wnl.0b013e31821f4447",
"authors": [
- ["Deepak", "Kumar"],
- ["Ashaq", "Hussain"],
- ["Achal K", "Srivastava"],
- ["Mitali", "Mukerji"],
- ["Odity", "Mukherjee"],
- ["Mohammed", "Faruq"]
+ ["T", "Lee"],
+ ["Y R", "Li"],
+ ["A", "Chesi"],
+ ["M P", "Hart"],
+ ["D", "Ramos"],
+ ["N", "Jethava"],
+ ["D", "Hosangadi"],
+ ["J", "Epstein"],
+ ["B", "Hodges"],
+ ["N M", "Bonini"],
+ ["A D", "Gitler"]
],
- "publisher": "Stem cell research",
- "issn": "1876-7753",
- "date": "2018-08-14",
- "abstract": "Spinocerebellar ataxia type-12 (SCA12) is a neurological disorder caused due to triplet (CAG) repeat expansion in 5' UTR of PPP2R2B. It is one of the most prominent SCA-subtype in Indian population and till date no patient specific models have been described. Human-induced-pluripotent-stem cell (HiPSC) based disease modelling has become the next generation tool for studying various human pathologies. In the present study we established three SCA12 patient specific iPSC lines. All the generated lines have shown pluripotency markers, normal karyotype, in-vitro three germ layers differentiation potential, vector clearance, SCA12 mutation, parental genomic identity and contamination free culture.",
+ "publisher": "Neurology",
+ "issn": "1526-632X",
+ "date": "2011-05-11",
+ "abstract": "Given the recent finding of an association between intermediate-length polyglutamine (polyQ) expansions in ataxin 2 and amyotrophic lateral sclerosis (ALS), we sought to determine whether expansions in other polyQ disease genes were associated with ALS.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30130680"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21562248"
},
{
- "id": "pmid:25586539",
+ "id": "pmid:21437269",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25586539",
- "title": "Unusual cerebral white matter change in a Chinese family with Spinocerebellar ataxia type 12.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21437269",
+ "title": "Triplet repeat-derived siRNAs enhance RNA-mediated toxicity in a Drosophila model for myotonic dystrophy.",
"type": "article-journal",
- "doi": "10.1016/j.jns.2014.12.045",
+ "doi": "10.1371/journal.pgen.1001340",
"authors": [
- ["Tao", "Hu"],
- ["Bi", "Zhao"],
- ["Qian-qian", "Wei"],
- ["Huifang", "Shang"]
+ ["Zhenming", "Yu"],
+ ["Xiuyin", "Teng"],
+ ["Nancy M", "Bonini"]
],
- "publisher": "Journal of the neurological sciences",
- "issn": "1878-5883",
- "date": "2015-01-05",
- "abstract": "In a Chinese family with Spinocerebellar ataxia type 12 (SCA12), presenting with action tremor, mild cerebellar dysfunction, and hyperreflexia, genetic testing revealed abnormal CAG repeat length in the brain-specific protein phosphatase 2, regulatory subunit B, beta isoform (PPP2R2B) gene. To our knowledge, this is the first report on patients with SCA12 presenting with prominent cerebral white matter change besides cerebral and/or cerebellar atrophy.",
+ "publisher": "PLoS genetics",
+ "issn": "1553-7404",
+ "date": "2011-03-17",
+ "abstract": "More than 20 human neurological and neurodegenerative diseases are caused by simple DNA repeat expansions; among these, non-coding CTG repeat expansions are the basis of myotonic dystrophy (DM1). Recent work, however, has also revealed that many human genes have anti-sense transcripts, raising the possibility that human trinucleotide expansion diseases may be comprised of pathogenic activities due both to a sense expanded-repeat transcript and to an anti-sense expanded-repeat transcript. We established a Drosophila model for DM1 and tested the role of interactions between expanded CTG transcripts and expanded CAG repeat transcripts. These studies revealed dramatically enhanced toxicity in flies co-expressing CTG with CAG expanded repeats. Expression of the two transcripts led to novel pathogenesis with the generation of dcr-2 and ago2-dependent 21-nt triplet repeat-derived siRNAs. These small RNAs targeted the expression of CAG-containing genes, such as Ataxin-2 and TATA binding protein (TBP), which bear long CAG repeats in both fly and man. These findings indicate that the generation of triplet repeat-derived siRNAs may dramatically enhance toxicity in human repeat expansion diseases in which anti-sense transcription occurs.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25586539"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21437269"
},
{
- "id": "pmid:25274186",
+ "id": "pmid:20587494",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25274186",
- "title": "Diffusion tensor imaging of spinocerebellar ataxia type 12.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/20587494",
+ "title": "Spinocerebellar ataxia type 17 associated with an expansion of 42 glutamine residues in TATA-box binding protein gene.",
"type": "article-journal",
- "doi": "10.12659/msm.891104",
+ "doi": "10.1136/jnnp.2009.180711",
"authors": [
- ["Haitao", "Li"],
- ["Jingjing", "Ma"],
- ["Xiaoning", "Zhang"]
+ ["D", "Nolte"],
+ ["E", "Sobanski"],
+ ["A", "Wissen"],
+ ["J U", "Regula"],
+ ["C", "Lichy"],
+ ["U", "M\u00fcller"]
],
- "publisher": "Medical science monitor : international medical journal of experimental and clinical research",
- "issn": "1643-3750",
- "date": "2014-10-02",
- "abstract": "Spinocerebellar ataxias (SCAs) are autosomal-dominant neurodegenerative diseases that are clinically and genetically heterogeneous. SCAs are characterized by a range of neurological symptoms. SCA12 is an autosomal-dominant (AD) ataxia caused by a CAG repeat expansion mutation in a presumed promoter region of the gene PPP2R2B in a non-coding region on chromosome 5q32. This study sought to determine changes in different positions in a single Uyghur SCA12 pedigree by measuring the apparent diffusion coefficient (ADC) and fractional anisotropy (FA).",
+ "publisher": "Journal of neurology, neurosurgery, and psychiatry",
+ "issn": "1468-330X",
+ "date": "2010-06-28",
+ "abstract": "Spinocerebellar ataxia type 17 (SCA17) is caused by abnormal expansions of CAG/CAA trinucleotides within the TATA-box binding protein gene (TBP). The currently accepted critical threshold of abnormal expansions is \u226543.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25274186"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20587494"
},
{
- "id": "pmid:20937954",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/20937954",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:20937954']' timed out after 3 seconds"
+ "id": "pmid:20199210",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/20199210",
+ "title": "A spinocerebellar ataxia family with expanded alleles in the TATA-binding protein gene and ataxin-3 gene.",
+ "type": "article-journal",
+ "doi": "10.3109/00207450903389149",
+ "authors": [
+ ["Qian", "Xu"],
+ ["Qinghua", "Li"],
+ ["Junling", "Wang"],
+ ["Hong", "Jiang"],
+ ["Lu", "Shen"],
+ ["Xiaohui", "Li"],
+ ["Beisha", "Tang"]
+ ],
+ "publisher": "The International journal of neuroscience",
+ "issn": "1563-5279",
+ "date": "2010-02-01",
+ "abstract": "We report on a Chinese family with three members who have CAG repeat expansion in the ataxin-3, two members present with expanded trinucleotide repeat in both the ataxin-3 and tata-binding protein (TBP) and an individual who carries expanded CAG/CAA repeat in the TBP. Only the patients who carry an allele with expansion in the ataxin-3 gene presented with clinical symptoms. This interesting family presents a unique mutation state. We will continue to track this family in the future, which may help us further elucidate the pathogenic mechanism of spinocerebellar ataxia (SCA) type 3 and 17. The study also provides us a novel conception that mutations from two pathogenetic genes may coexist in one patient and SCA-affected patients with intermediate allele need to be further excluded for other SCA subtypes.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20199210"
},
{
- "id": "pmid:18484086",
+ "id": "pmid:20004653",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/18484086",
- "title": "PPP2R2B CAG repeat length in the Han Chinese in Taiwan: Association analyses in neurological and psychiatric disorders and potential functional implications.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/20004653",
+ "title": "SCA17 repeat expansion: mildly expanded CAG/CAA repeat alleles in neurological disorders and the functional implications.",
"type": "article-journal",
- "doi": "10.1002/ajmg.b.30785",
+ "doi": "10.1016/j.cca.2009.12.002",
"authors": [
["Chiung-Mei", "Chen"],
- ["Yi-Ting", "Hou"],
- ["Ju-Yun", "Liu"],
- ["Yih-Ru", "Wu"],
- ["Chih-Hsin", "Lin"],
+ ["Li-Ching", "Lee"],
+ ["Bing-Wen", "Soong"],
["Hon-Chung", "Fung"],
["Wen-Chuin", "Hsu"],
- ["Yuying", "Hsu"],
- ["Shen-Hung", "Lee"],
- ["Hsiu-Mei", "Hsieh-Li"],
- ["Ming-Tsan", "Su"],
- ["Shui-Tein", "Chen"],
- ["Hsien-Yuan", "Lane"],
- ["Guey-Jen", "Lee-Chen"]
+ ["Pei-Ying", "Lin"],
+ ["Hui-Ju", "Huang"],
+ ["Fen-Lin", "Chen"],
+ ["Cheng-Yueh", "Lin"],
+ ["Guey-Jen", "Lee-Chen"],
+ ["Yih-Ru", "Wu"]
],
- "publisher": "American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics",
- "issn": "1552-485X",
- "date": "2009-01-05",
- "abstract": "PPP2R2B, a protein widely expressed in neurons throughout the brain, regulates the protein phosphatase 2A (PP2A) activity for the microtubule-associated protein tau and other substrates. Altered PP2A activity has been implicated in spinocerebellar ataxia 12, Alzheimer's disease (AD), and other tauopathies. Through a case-control study and a reporter assay, we investigated the association of PPP2R2B CAG repeat polymorphism with Taiwanese AD, essential tremor (ET), Parkinson's disease (PD), and schizophrenia and clarified the functional implication of this polymorphism. The distribution of the alleles was not significantly different between patients and controls, with 68.6-76.1% alleles at lengths of 10, 13, and 16 triplets. No expanded alleles were detected in either group. However, the frequency of the individuals carrying the short 5-, 6-, and 7-triplet alleles was notably higher in patients with AD (5/180 [2.8%], Fisher's exact test, P = 0.003; including 2 homozygotes) and ET (4/132 [3.0%], Fisher's exact test, P < 0.001) than in the controls (1/625 [0.2%]). The PPP2R2B transcriptional activity was significantly lower in the luciferase reporter constructs containing the (CAG)(5-7) allele than in those containing the common 10-, 13-, and 16-triplet alleles in both neuroblastoma and embryonic kidney cells. Therefore, our preliminary results suggest that the PPP2R2B gene CAG repeat polymorphism may be functional and may, in part, play a role in conferring susceptibility to AD and ET in Taiwan.",
+ "publisher": "Clinica chimica acta; international journal of clinical chemistry",
+ "issn": "1873-3492",
+ "date": "2009-12-11",
+ "abstract": "Spinocerebellar ataxia type 17 (SCA17) involves the expression of a CAG/CAA expansion mutation in the gene encoding TATA-box binding protein (TBP), a general transcription initiation factor. The spectrum of SCA17 clinical presentation is broad.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18484086"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20004653"
},
{
- "id": "pmid:11171892",
+ "id": "pmid:19566714",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/11171892",
- "title": "SCA-12: Tremor with cerebellar and cortical atrophy is associated with a CAG repeat expansion.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19566714",
+ "title": "TATA box-binding protein gene is associated with risk for schizophrenia, age at onset and prefrontal function.",
"type": "article-journal",
- "doi": "10.1212/wnl.56.3.299",
+ "doi": "10.1111/j.1601-183x.2009.00497.x",
"authors": [
- ["E", "O'Hearn"],
- ["S E", "Holmes"],
- ["P C", "Calvert"],
- ["C A", "Ross"],
- ["R L", "Margolis"]
+ ["K", "Ohi"],
+ ["R", "Hashimoto"],
+ ["Y", "Yasuda"],
+ ["M", "Kiribayashi"],
+ ["N", "Iike"],
+ ["T", "Yoshida"],
+ ["M", "Azechi"],
+ ["K", "Ikezawa"],
+ ["H", "Takahashi"],
+ ["T", "Morihara"],
+ ["R", "Ishii"],
+ ["S", "Tagami"],
+ ["M", "Iwase"],
+ ["M", "Okochi"],
+ ["K", "Kamino"],
+ ["H", "Kazui"],
+ ["T", "Tanaka"],
+ ["T", "Kudo"],
+ ["M", "Takeda"]
],
- "publisher": "Neurology",
- "issn": "0028-3878",
- "date": "2001-02-13",
- "abstract": "To characterize the clinical and neuroradiologic features of a new spinocerebellar ataxia, SCA-12, in the index family.",
+ "publisher": "Genes, brain, and behavior",
+ "issn": "1601-183X",
+ "date": "2009-06-01",
+ "abstract": "Schizophrenia is a common polygenic disease in distinct populations, while spinocerebellar ataxia type 17 (SCA17) is a rare autosomal dominant neurodegenerative disorder. Both diseases involve psychotic symptoms. SCA17 is caused by an expanded polyglutamine tract in the TATA box-binding protein (TBP) gene. In the present study, we investigated the association between schizophrenia and CAG repeat length in common TBP alleles with fewer than 42 CAG repeats in a Japanese population (326 patients with schizophrenia and 116 healthy controls). We found that higher frequency of alleles with greater than 35 CAG repeats in patients with schizophrenia compared with that in controls (p = 0.042). We also examined the correlation between CAG repeats length and age at onset of schizophrenia. We observed a negative correlation between the number of CAG repeats in the chromosome with longer CAG repeats out of two chromosomes and age at onset of schizophrenia (p = 0.020). We further provided evidence that TBP genotypes with greater than 35 CAG repeats, which were enriched in patients with schizophrenia, were significantly associated with hypoactivation of the prefrontal cortex measured by near-infrared spectroscopy during the tower of Hanoi, a task of executive function (right PFC; p = 0.015, left PFC; p = 0.010). These findings suggest possible associations of the genetic variations of the TBP gene with risk for schizophrenia, age at onset and prefrontal function.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11171892"
-},
-{
- "id": "pmid:29939637",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/29939637",
- "note": "WARNING: Couldn't parse Manubot response: list index out of range"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19566714"
},
{
- "id": "pmid:35585119",
+ "id": "pmid:18218637",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/35585119",
- "title": "Prion protein gene mutation detection using long-read Nanopore sequencing.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18218637",
+ "title": "Polyglutamine expansion reduces the association of TATA-binding protein with DNA and induces DNA binding-independent neurotoxicity.",
"type": "article-journal",
- "doi": "10.1038/s41598-022-12130-7",
+ "doi": "10.1074/jbc.m709674200",
"authors": [
- ["Fran\u00e7ois", "Kroll"],
- ["Athanasios", "Dimitriadis"],
- ["Tracy", "Campbell"],
- ["Lee", "Darwent"],
- ["John", "Collinge"],
- ["Simon", "Mead"],
- ["Emmanuelle", "Vire"]
+ ["Meyer J", "Friedman"],
+ ["Chuan-En", "Wang"],
+ ["Xiao-Jiang", "Li"],
+ ["Shihua", "Li"]
],
- "publisher": "Scientific reports",
- "issn": "2045-2322",
- "date": "2022-05-18",
- "abstract": "Prion diseases are fatal neurodegenerative conditions that affect humans and animals. Rapid and accurate sequencing of the prion gene PRNP is paramount to human prion disease diagnosis and for animal surveillance programmes. Current methods for PRNP genotyping involve sequencing of small fragments within the protein-coding region. The contribution of variants in the non-coding regions of PRNP including large structural changes is poorly understood. Here, we used long-range PCR and Nanopore sequencing to sequence the full length of PRNP, including its regulatory region, in 25 samples from blood and brain of individuals with inherited or sporadic prion diseases. Nanopore sequencing detected the same variants as identified by Sanger sequencing, including repeat expansions/deletions. Nanopore identified additional single-nucleotide variants in the non-coding regions of PRNP, but no novel structural variants were discovered. Finally, we explored somatic mosaicism of PRNP's octapeptide repeat region, which is a hypothetical cause of sporadic prion disease. While we found changes consistent with somatic mutations, we demonstrate that they may have been generated by the PCR. Our study illustrates the accuracy of Nanopore sequencing for rapid and field prion disease diagnosis and highlights the need for single-molecule sequencing methods for the detection of somatic mutations.",
+ "publisher": "The Journal of biological chemistry",
+ "issn": "0021-9258",
+ "date": "2008-01-24",
+ "abstract": "TATA-binding protein (TBP) is essential for eukaryotic gene transcription. Human TBP contains a polymorphic polyglutamine (polyQ) domain in its N terminus and a DNA-binding domain in its highly conserved C terminus. Expansion of the polyQ domain to >42 glutamines typically results in spinocerebellar ataxia type 17 (SCA17), a neurodegenerative disorder that resembles Huntington disease. Our recent studies have demonstrated that polyQ expansion causes abnormal interaction of TBP with the general transcription factor TFIIB and induces neurodegeneration in transgenic SCA17 mice (Friedman, M. J., Shah, A. G., Fang, Z. H., Ward, E. G., Warren, S. T., Li, S., and Li, X. J. (2007) Nat. Neurosci. 10, 1519-1528). However, it remains unknown how polyQ expansion influences DNA binding by TBP. Here we report that polyQ expansion reduces in vitro binding of TBP to DNA and that mutant TBP fragments lacking an intact C-terminal DNA-binding domain are present in transgenic SCA17 mouse brains. polyQ-expanded TBP with a deletion spanning part of the DNA-binding domain does not bind DNA in vitro but forms nuclear aggregates and inhibits TATA-dependent transcription activity in cultured cells. When this TBP double mutant is expressed in transgenic mice, it forms nuclear inclusions in neurons and causes early death. These findings suggest that the polyQ tract affects the binding of TBP to promoter DNA and that polyQ-expanded TBP can induce neuronal toxicity independent of its interaction with DNA.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35585119"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18218637"
},
{
- "id": "pmid:21686668",
+ "id": "pmid:16223509",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21686668",
- "title": "De novo seven extra repeat expanded mutation in the PRNP gene in an Italian patient with early onset dementia.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/16223509",
+ "title": "Minimum prevalence of spinocerebellar ataxia 17 in the north east of England.",
"type": "article-journal",
- "doi": "10.1136/bcr.08.2008.0711",
+ "doi": "10.1016/j.jns.2005.08.009",
"authors": [
- ["M", "Cannella"],
- ["Tiziana", "Martino"],
- ["Maria", "Simonelli"],
- ["Andrea", "Ciammola"],
- ["Roberto", "Gradini"],
- ["Andrea", "Ciarmiello"],
- ["Fernando", "Gianfrancesco"],
- ["Ferdinando", "Squitieri"]
+ ["Kate", "Craig"],
+ ["Sharon M", "Keers"],
+ ["Timothy J", "Walls"],
+ ["Anne", "Curtis"],
+ ["Patrick F", "Chinnery"]
],
- "publisher": "BMJ case reports",
- "issn": "1757-790X",
- "date": "2009-02-02",
- "abstract": "Point and octapeptide repeat (24 bp) insertional mutations in the prion protein gene (PRNP) cause a dominantly transmitted dementia, associated with spongiform degeneration of the brain, astrocytic gliosis and neuronal loss due to cell accumulation of mutated protease resistant prion protein. The octapeptide repeat region lies between codon 51 and 91, and comprises a nonapeptide followed by a tandem repeat containing four copies of an octapeptide. The normal tandem length in healthy individuals is five repeats R1-R2-R2-R3-R4, but mutations can contain up to nine additional extra repeats. Some insight into this genetic mechanism comes from the de novo meiotic insertional extra repeat mutation in PRNP we detected in a patient whose parents had a normal phenotype and a wild-type sequence in the same gene. To our knowledge, this is the first time this condition has been described.",
+ "publisher": "Journal of the neurological sciences",
+ "issn": "0022-510X",
+ "date": "2005-10-11",
+ "abstract": "To determine the minimum prevalence of spinocerebellar ataxia type 17 (SCA17) in the north east of England.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21686668"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16223509"
},
{
- "id": "pmid:19092329",
+ "id": "pmid:15850778",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/19092329",
- "title": "A patient with Creutzfeldt-Jakob disease with an insertion of 7 octa-repeats in the PRNP gene: molecular characteristics and clinical features.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15850778",
+ "title": "No evidence for association of the TATA-box binding protein glutamine repeat sequence or the flanking chromosome 6q27 region with type 1 diabetes.",
"type": "article-journal",
- "doi": "10.1097/maj.0b013e3181643e50",
+ "doi": "10.1016/j.bbrc.2005.03.203",
"authors": [
- ["Yan-Jun", "Guo"],
- ["Xiao-Fan", "Wang"],
- ["Jun", "Han"],
- ["Bao-Yun", "Zhang"],
- ["Wei-Qin", "Zhao"],
- ["Qi", "Shi"],
- ["Yan-Zhen", "Wan"],
- ["Chen", "Gao"],
- ["Ji-Mei", "Li"],
- ["De-Xin", "Wang"],
- ["Xiao-Ping", "Dong"]
+ ["Felicity", "Payne"],
+ ["Deborah J", "Smyth"],
+ ["Rebecca", "Pask"],
+ ["Jason D", "Cooper"],
+ ["Jennifer", "Masters"],
+ ["William Y S", "Wang"],
+ ["Lisa M", "Godfrey"],
+ ["Georgina", "Bowden"],
+ ["Jeffrey", "Szeszko"],
+ ["Luc J", "Smink"],
+ ["Alex C", "Lam"],
+ ["Oliver", "Burren"],
+ ["Neil M", "Walker"],
+ ["Sarah", "Nutland"],
+ ["Helen", "Rance"],
+ ["Dag E", "Undlien"],
+ ["Kjersti S", "R\u00f8nningen"],
+ ["Cristian", "Guja"],
+ ["Constantin", "Ionescu-T\u00eergovi\u015fte"],
+ ["John A", "Todd"],
+ ["Rebecca C J", "Twells"]
],
- "publisher": "The American journal of the medical sciences",
- "issn": "0002-9629",
- "date": "2008-12-01",
- "abstract": "We evaluated the features of neuropathology, abnormal prion protein (PrP) molecules, and clinical data of a Chinese woman diagnosed with familiar Creutzfeldt-Jakob disease (CJD), having 7 octa-repeats inserted with codon 129 methionine homozygote in the PRNP gene.",
+ "publisher": "Biochemical and biophysical research communications",
+ "issn": "0006-291X",
+ "date": "2005-06-03",
+ "abstract": "Susceptibility to the autoimmune disease type 1 diabetes has been linked to human chromosome 6q27 and, moreover, recently associated with one of the genes in the region, TATA box-binding protein (TBP). Using a much larger sample of T1D families than those studied by others, and by extensive re-sequencing of nine other genes in the proximity, in which we identified 279 polymorphisms, 83 of which were genotyped in up to 725 T1D multiplex and simplex families, we obtained no evidence for association of the TBP CAG/CAA (glutamine) microsatellite repeat sequence with disease, or for nine other genes, PDCD2, PSMB1, KIAA1838, DLL1, dJ894D12.4, FLJ25454, FLJ13162, FLJ11152, PHF10 and CCR6. This study also provides an exon-based tag single nucleotide polymorphism map for these 10 genes that can be used for analysis of other diseases.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19092329"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15850778"
},
{
- "id": "pmid:18366654",
+ "id": "pmid:15503103",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/18366654",
- "title": "Prion protein insertional mutations increase aggregation propensity but not fiber stability.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15503103",
+ "title": "Mutation at the SCA17 locus is not a common cause of primary dystonia.",
"type": "article-journal",
- "doi": "10.1186/1471-2091-9-7",
+ "doi": "10.1007/s00415-004-0520-2",
"authors": [
- ["Tejas", "Kalastavadi"],
- ["Heather L", "True"]
+ ["Kathrin", "Grundmann"],
+ ["Ulrike", "Laubis-Herrmann"],
+ ["Dirk", "Dressler"],
+ ["Juliane", "Vollmer-Haase"],
+ ["Peter", "Bauer"],
+ ["Manfred", "Stuhrmann"],
+ ["Thorsten", "Schulte"],
+ ["Ludger", "Sch\u00f6ls"],
+ ["Helge", "Topka"],
+ ["Olaf", "Riess"]
],
- "publisher": "BMC biochemistry",
- "issn": "1471-2091",
- "date": "2008-03-17",
- "abstract": "Mutations in the PRNP gene account for ~15% of all prion disease cases. Little is understood about the mechanism of how some of these mutations in PRNP cause the protein to aggregate into amyloid fibers or cause disease. We have taken advantage of a chimeric protein system to study the oligopeptide repeat domain (ORD) expansions of the prion protein, PrP, and their effect on protein aggregation and amyloid fiber formation. We replaced the ORD of the yeast prion protein Sup35p with that from wild type and expanded ORDs of PrP and compared their biochemical properties in vitro. We previously determined that these chimeric proteins maintain the [PSI+] yeast prion phenotype in vivo. Interestingly, we noted that the repeat expanded chimeric prions seemed to be able to maintain a stronger strain of [PSI+] and convert from [psi-] to [PSI+] with a much higher frequency. In this study we have attempted to understand the biochemical properties of these chimeric proteins and to establish a system to study the properties of the ORD of PrP both in vivo and in vitro.",
+ "publisher": "Journal of neurology",
+ "issn": "0340-5354",
+ "date": "2004-10-01",
+ "abstract": "Spinocerebellar ataxia type 17 (SCA17) is a dominant progressive neurodegenerative disorder, caused by a triplet repeat expansion within the TATA-binding protein. As well as ataxia and dementia, Parkinsonism and dystonia are common in SCA17. In some pedigrees focal dystonia in the absence of ataxia has been described as a main clinical feature. To evaluate the relevance of SCA17 mutations for primary dystonia, we examined the TBP repeat expansion in a series of 288 patients with different subtypes of primary torsion dystonia. We did not find any repeat sizes in the pathogenic range. We conclude that the SCA17 repeat expansion is not a common cause of familial and sporadic dystonia.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18366654"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15503103"
},
{
- "id": "pmid:14729275",
+ "id": "pmid:15381080",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/14729275",
- "title": "A processed pseudogene contributes to apparent mule deer prion gene heterogeneity.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15381080",
+ "title": "Association of a CAG/CAA repeat sequence in the TBP gene with type I diabetes.",
"type": "article-journal",
- "doi": "10.1016/j.gene.2003.10.022",
+ "doi": "10.1016/j.bbrc.2004.08.159",
"authors": [
- ["Kelly A", "Brayton"],
- ["Katherine I", "O'Rourke"],
- ["Amy K", "Lyda"],
- ["Michael W", "Miller"],
- ["Donald P", "Knowles"]
+ ["David", "Owerbach"],
+ ["Lazaro", "Pi\u00f1a"],
+ ["Kenneth H", "Gabbay"]
],
- "publisher": "Gene",
- "issn": "0378-1119",
- "date": "2004-02-04",
- "abstract": "Pathogenesis and transmission of the prion disorders (transmissible spongiform encephalopathies, TSEs) are mediated by a modified isoform of the prion protein (PrP). Prion protein gene (PRNP) alleles associated with relative susceptibility to TSE have been identified in sheep, humans and possibly elk. Comparable data have not been derived for mule deer, a species susceptible to the TSE chronic wasting disease (CWD). Initial analysis of the open reading frame (ORF) in exon 3 of the mule deer PRNP gene revealed polymorphisms in all 145 samples analyzed, with 10 potential polymorphic sites. Because 144/145 (99.3%) of the samples were heterozygous for a coding change (N/S) at codon 138 (bp 412) and a non-coding polymorphism at bp 418, and individual deer with three or four different alleles were identified a possible gene duplication was indicated. Analysis of BAC clones containing mule deer PRNP genes revealed a full length functional gene and a processed pseudogene. The pseudogene was characteristic of previously described retroelements, in that it lacks introns and is flanked by repeat sequences. Three alleles of the functional gene were identified, with coding changes only at codons 20 (D/G) and 225 (S/F). Determination of PRNP functional gene alleles from 47 CWD-positive mule deer showed the predominant allele encoded 20D225S (frequency 0.85). When alleles were grouped by coding changes in the functional gene, four of the six possible peptide combinations were identified in infected deer. Three pseudogene alleles with coding changes in exon 3 were identified in the mule deer samples examined. Because the TSEs appear to be \"protein only\" disorders, the presence of an untranslated pseudogene is not expected to affect disease resistance. Therefore, selection of a genotyping method specific for the functional gene is critical for large-scale studies to identify the role of the PRNP gene in susceptibility to CWD in mule deer.",
+ "publisher": "Biochemical and biophysical research communications",
+ "issn": "0006-291X",
+ "date": "2004-10-22",
+ "abstract": "Type I diabetes is a complex disease in which multiple susceptibility loci have been implicated by whole genome scans. IDDM8, a susceptibility locus, is located on chromosome 6q27, however the specific susceptibility gene has yet to be identified. We have examined five potential candidate genes using 36 genetic markers, spanning 360kb located near the chromosome 6q27 terminus in 478 families for diabetes association. No associations with type I diabetes susceptibility were detected with the strength previously observed for IDDM1 or IDDM2. However, a novel CAG/CAA polymorphism was detected in exon 3 of the TATA box-binding protein gene, which shows preliminary evidence of association with diabetes susceptibility (p<0.05).",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:14729275"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15381080"
},
{
- "id": "pmid:12451210",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/12451210",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:12451210']' timed out after 3 seconds"
+ "id": "pmid:14985389",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/14985389",
+ "title": "Trinucleotide repeat expansion in SCA17/TBP in white patients with Huntington's disease-like phenotype.",
+ "type": "article-journal",
+ "doi": "10.1136/jmg.2003.015602",
+ "authors": [
+ ["P", "Bauer"],
+ ["F", "Laccone"],
+ ["A", "Rolfs"],
+ ["U", "W\u00fcllner"],
+ ["S", "B\u00f6sch"],
+ ["H", "Peters"],
+ ["S", "Liebscher"],
+ ["M", "Scheible"],
+ ["J T", "Epplen"],
+ ["B H F", "Weber"],
+ ["E", "Holinski-Feder"],
+ ["H", "Weirich-Schwaiger"],
+ ["D J", "Morris-Rosendahl"],
+ ["J", "Andrich"],
+ ["O", "Riess"]
+ ],
+ "publisher": "Journal of medical genetics",
+ "issn": "1468-6244",
+ "date": "2004-03-01",
+ "abstract": "",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:14985389"
},
{
- "id": "pmid:9710033",
+ "id": "pmid:12953269",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/9710033",
- "title": "APOE in non-Alzheimer amyloidoses: transmissible spongiform encephalopathies.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/12953269",
+ "title": "Clinical features and neuropathology of autosomal dominant spinocerebellar ataxia (SCA17).",
"type": "article-journal",
- "doi": "10.1212/wnl.51.2.548",
+ "doi": "10.1002/ana.10676",
"authors": [
- ["J", "Chapman"],
- ["L", "Cerven\u00e1kov\u00e1"],
- ["R B", "Petersen"],
- ["H S", "Lee"],
- ["J", "Estupinan"],
- ["S", "Richardson"],
- ["C L", "Vnencak-Jones"],
- ["D C", "Gajdusek"],
- ["A D", "Korczyn"],
- ["P", "Brown"],
- ["L G", "Goldfarb"]
+ ["Arndt", "Rolfs"],
+ ["Arnulf H", "Koeppen"],
+ ["Ingrid", "Bauer"],
+ ["Peter", "Bauer"],
+ ["Sven", "Buhlmann"],
+ ["Helge", "Topka"],
+ ["Ludger", "Sch\u00f6ls"],
+ ["Olaf", "Riess"]
],
- "publisher": "Neurology",
- "issn": "0028-3878",
- "date": "1998-08-01",
- "abstract": "The APOE genotype has been shown to influence the risk of developing sporadic and familial AD. This effect is isoform-dependent, the APOE epsilon4 allele increasing susceptibility and the APOE epsilon2 allele providing protection. Amyloid formation is an important part of the pathogenesis in AD as well as in spongiform encephalopathies; apoE deposition in amyloid plaques has been documented in both conditions.",
+ "publisher": "Annals of neurology",
+ "issn": "0364-5134",
+ "date": "2003-09-01",
+ "abstract": "Autosomal dominant spinocerebellar ataxias (SCAs) are a group of neurodegenerative disorders clinically characterized by late-onset ataxia and variable other manifestations. Genetically and clinically, SCA is highly heterogeneous. Recently, CAG repeat expansions in the gene encoding TATA-binding protein (TBP) have been found in a new form of SCA, which has been designated SCA17. To estimate the frequency of SCA17 among white SCA patients and to define the phenotypic variability, we determined the frequency of SCA17 in a large sample of 1,318 SCA patients. In total, 15 patients in four autosomal dominant SCA families had CAG/CAA repeat expansions in the TBP gene ranging from 45 to 54 repeats. The clinical features of our SCA17 patients differ from other SCA types by manifesting with psychiatric abnormalities and dementia. The neuropathology of SCA17 can be classified as a \"pure cerebellar\" or \"cerebello-olivary\" form of ataxia. However, intranuclear neuronal inclusion bodies with immunoreactivity to anti-TBP and antipolyglutamine were much more widely distributed throughout the brain gray matter than in other SCAs. Based on clinical and genetic data, we conclude that SCA17 is rare among white SCA patients. SCA17 should be considered in sporadic and familial cases of ataxia with accompanying psychiatric symptoms and dementia.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9710033"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12953269"
},
{
- "id": "pmid:9565627",
+ "id": "pmid:12891385",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/9565627",
- "title": "Abnormal properties of prion protein with insertional mutations in different cell types.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/12891385",
+ "title": "SCA17 caused by homozygous repeat expansion in TBP due to partial isodisomy 6.",
"type": "article-journal",
- "doi": "10.1074/jbc.273.19.11980",
+ "doi": "10.1038/sj.ejhg.5201018",
"authors": [
- ["S A", "Priola"],
- ["B", "Chesebro"]
+ ["C H", "Z\u00fchlke"],
+ ["M", "Spranger"],
+ ["S", "Spranger"],
+ ["R", "Voigt"],
+ ["M", "Lanz"],
+ ["U", "Gehlken"],
+ ["F", "Hinrichs"],
+ ["E", "Schwinger"]
],
- "publisher": "The Journal of biological chemistry",
- "issn": "0021-9258",
- "date": "1998-05-08",
- "abstract": "Inherited forms of the human transmissible spongiform encephalopathy Creutzfeldt-Jakob disease (CJD) have been associated with mutations in the normal soluble, protease-sensitive form of the host prion protein (PrP-sen). Normal PrP protein contains five copies of a repeating eight-amino acid region, and PrP molecules with six or more copies of this region are associated with disease in familial CJD. It has been hypothesized that these mutations might facilitate spontaneous formation of the abnormal, aggregated protease-resistant PrP isoform, PrP-res, associated with clinical CJD and other transmissible spongiform encephalopathies (TSE). In the present experiments, hamster PrP molecules with 5 (wild-type), 7, 9, or 11 copies of this repeat region were generated and expressed in mouse fibroblast cells or mouse neuroblastoma cells. In mouse fibroblast cells, mutant hamster PrP molecules expressing 7, 9, and 11 copies of the octapeptide repeat sequence showed altered cell surface expression, but both mutant and wild-type hamster PrP-sen molecules demonstrated abnormal properties of aggregation and increased protease resistance. By contrast in mouse neuroblastoma cells, hamster PrP-sen with 5, 9, and 11 octapeptide repeats were expressed normally on the cell surface, but only PrP-sen molecules with 9 or 11 copies of the repeat motif had abnormal properties of aggregation and increased protease resistance. Overall, regardless of cell type, hamster PrP molecules with greater than 7 octapeptide repeats were more aggregated and more protease-resistant than molecules with 7 repeats or less. However, these abnormal molecules were at least 1000-fold less protease-resistant than bona fide PrP-res derived from TSE-infected brain tissue, and they showed no increased ability to form PrP-res in a cell-free system.",
+ "publisher": "European journal of human genetics : EJHG",
+ "issn": "1018-4813",
+ "date": "2003-08-01",
+ "abstract": "An expanded polyglutamine domain in the TATA-binding protein (TBP) has been described in patients with spinocerebellar ataxia type 17 (SCA17) characterized by cerebellar ataxia associated with dementia. TBP is a general transcription initiation factor that regulates the expression of most eukaryotic genes transcribed by RNA polymerase II. SCA17, as an autosomal dominantly inherited progressive neurodegenerative disorder, is caused by heterozygous expansion of a CAG repeat coding for glutamine. Alleles with 27 to a maximum of 44 glutamine residues were found as the normal range, whereas expansions above 45 repeat units were considered pathological. Here, we present a patient with a very severe phenotype with a late onset but rapidly progressing ataxia associated with dementia and homozygous 47 glutamine residues caused by an apparent partial isodisomy 6. This extraordinary case has important implications for the insights of TBP and SCA17. The expanded polyglutamine domain in both TBP copies is not correlated with embryonic death indicating that the normal function of the protein is not disrupted by this kind of mutation but may account for the dementia seen in this patient.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9565627"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12891385"
},
{
- "id": "pmid:33186760",
+ "id": "pmid:11313753",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/33186760",
- "title": "Digestive involvement in a severe form of Snyder-Robinson syndrome: Possible expansion of the phenotype.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11313753",
+ "title": "Different types of repeat expansion in the TATA-binding protein gene are associated with a new form of inherited ataxia.",
"type": "article-journal",
- "doi": "10.1016/j.ejmg.2020.104097",
+ "doi": "10.1038/sj.ejhg.5200617",
"authors": [
- ["Pauline", "Dontaine"],
- ["Elisa", "Kottos"],
- ["Martine", "Dassonville"],
- ["Ovidiu", "Balasel"],
- ["V\u00e9ronique", "Catros"],
- ["Julie", "Soblet"],
- ["Pascale", "Perlot"],
- ["Catheline", "Vilain"]
+ ["C", "Z\u00fchlke"],
+ ["Y", "Hellenbroich"],
+ ["A", "Dalski"],
+ ["N", "Kononowa"],
+ ["J", "Hagenah"],
+ ["P", "Vieregge"],
+ ["O", "Riess"],
+ ["C", "Klein"],
+ ["E", "Schwinger"]
],
- "publisher": "European journal of medical genetics",
- "issn": "1878-0849",
- "date": "2020-11-10",
- "abstract": "Snyder-Robinson syndrome (OMIM #309583) is a rare X-linked condition, caused by mutation in the SMS gene (MIM *300105), characterized by a wide spectrum of clinical signs including developmental delay, epilepsy, asthenic habitus, dysmorphism, osteopenia, and renal or genital anomalies. Here we describe two maternal half-brothers who both presented with severe neurodevelopmental delay, seizures, hearing loss, facial dysmorphism, renal and ophthalmologic anomalies, failure to thrive and premature death. A novel p.(Gly203Asp) variant was found at the hemizygous state in the two boys, and an elevated Spermidine/Spermine ratio confirmed the diagnosis of Snyder-Robinson syndrome. One of the brothers presented with gastrointestinal symptoms, with jejunal stenosis, enteral feeding intolerance, failure to thrive due to a dysfunctional gastrointestinal system, cholestasis and exocrine pancreatic insufficiency. Although more studies will be needed to understand its mechanisms, this observation lends further support to the possibility of severe digestive involvement in Snyder Robinson syndrome.",
+ "publisher": "European journal of human genetics : EJHG",
+ "issn": "1018-4813",
+ "date": "2001-03-01",
+ "abstract": "A novel neurological syndrome has recently been described to be associated with an expanded polyglutamine domain. The expansion results from partial duplication within the TATA-binding protein (TBP). By investigation of 604 sporadic and familial cases with various forms of neurological syndromes and 157 unaffected individuals, we found repeat expansions in the TBP in four patients of two families with autosomal dominant inheritance of ataxia, dystonia, and intellectual decline. Two different genotypes for the repetitive sequence could be demonstrated which led to elongated polyglutamine stretches between 50 and 55 residues, whereas normal alleles with 27 to a maximum of 44 glutamine residues were found in this study. The expansion to 50 or more glutamine residues results in a pathological phenotype and confirms the report of a new polyglutamine disease.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33186760"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11313753"
},
{
- "id": "pmid:32283749",
+ "id": "pmid:9399691",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/32283749",
- "title": "Expansion and Conservation of Biosynthetic Gene Clusters in Pathogenic",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9399691",
+ "title": "No evidence for expanded polyglutamine sequences in bipolar disorder and schizophrenia.",
"type": "article-journal",
- "doi": "10.3390/toxins12040242",
+ "doi": "10.1038/sj.mp.4000297",
"authors": [
- ["Paula M", "Moolhuijzen"],
- ["Mariano Jordi", "Muria-Gonzalez"],
- ["Robert", "Syme"],
- ["Catherine", "Rawlinson"],
- ["Pao Theen", "See"],
- ["Caroline S", "Moffat"],
- ["Simon R", "Ellwood"]
+ ["A L", "Jones"],
+ ["F", "Middle"],
+ ["C", "Guy"],
+ ["G", "Spurlock"],
+ ["N J", "Cairns"],
+ ["P", "McGuffin"],
+ ["N", "Craddock"],
+ ["M", "Owen"],
+ ["M C", "O'Donovan"]
],
- "publisher": "Toxins",
- "issn": "2072-6651",
- "date": "2020-04-09",
- "abstract": "",
+ "publisher": "Molecular psychiatry",
+ "issn": "1359-4184",
+ "date": "1997-01-01",
+ "abstract": "Several recent studies have suggested that expanded CAG repeats may contribute to the genetic transmission of bipolar disorder and schizophrenia. In all known disorders associated with expanded CAG repeats, the repeat sequence is translated into glutamine. Therefore the simplest hypothesis is that one or more proteins with expanded polyglutamine sequences are involved in the pathogenesis of bipolar disorder and schizophrenia. In order to examine this hypothesis, we have used an antibody against expanded polyglutamine sequences to examine Western blots prepared from lymphoblastoid cell lines of patients with schizophrenia and bipolar disorder. We also examined Western blots prepared from left frontal cortex tissue samples obtained from 11 schizophrenics post mortem. With the exception of the TATA-binding protein (TBP), we did not detect any proteins containing expanded polyglutamine sequences. Our data therefore suggest either that the expanded repeats which are associated with these disorders do not encode polyglutamine, or that they are within genes that are not expressed within the tissues investigated here.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32283749"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9399691"
},
{
- "id": "pmid:30622881",
+ "id": "pmid:8886170",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/30622881",
- "title": "Comparative genomics of",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/8886170",
+ "title": "Analysis of polyglutamine-coding repeats in the TATA-binding protein in different human populations and in patients with schizophrenia and bipolar affective disorder.",
"type": "article-journal",
- "doi": "10.5598/imafungus.2018.09.02.02",
+ "doi": "10.1002/(sici)1096-8628(19960920)67:5<495::aid-ajmg12>3.0.co;2-i",
"authors": [
- ["Bo", "Wang"],
- ["Xiaofei", "Liang"],
- ["Mark L", "Gleason"],
- ["Rong", "Zhang"],
- ["Guangyu", "Sun"]
+ ["D C", "Rubinsztein"],
+ ["J", "Leggo"],
+ ["T J", "Crow"],
+ ["L E", "DeLisi"],
+ ["C", "Walsh"],
+ ["S", "Jain"],
+ ["E S", "Paykel"]
],
- "publisher": "IMA fungus",
- "issn": "2210-6340",
- "date": "2018-08-20",
- "abstract": "Ring rot, one of the most destructive diseases of apple worldwide, is caused primarily by",
+ "publisher": "American journal of medical genetics",
+ "issn": "0148-7299",
+ "date": "1996-09-20",
+ "abstract": "A new class of disease (including Huntington disease, Kennedy disease, and spinocerebellar ataxias types 1 and 3) results from abnormal expansions of CAG trinucleotides in the coding regions of genes. In all of these diseases the CAG repeats are thought to be translated into polyglutamine tracts. There is accumulating evidence arguing for CAG trinucleotide expansions as one of the causative disease mutations in schizophrenia and bipolar affective disorder. We and others believe that the TATA-binding protein (TBP) is an important candidate to investigate in these diseases as it contains a highly polymorphic stretch of glutamine codons, which are close to the threshold length where the polyglutamine tracts start to be associated with disease. Thus, we examined the lengths of this polyglutamine repeat in normal unrelated East Anglians, South African Blacks, sub-Saharan Africans mainly from Nigeria, and Asian Indians. We also examined 43 bipolar affective disorder patients and 65 schizophrenic patients. The range of polyglutamine tractlengths that we found in humans was from 26-42 codons. No patients with bipolar affective disorder and schizophrenia had abnormal expansions at this locus.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30622881"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8886170"
},
{
- "id": "pmid:25663198",
+ "id": "pmid:16141220",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25663198",
- "title": "Derivation, Expansion, and Motor Neuron Differentiation of Human-Induced Pluripotent Stem Cells with Non-Integrating Episomal Vectors and a Defined Xenogeneic-free Culture System.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/16141220",
+ "title": "Timed mutation and cell-fate mapping reveal reiterated roles of Tbx1 during embryogenesis, and a crucial function during segmentation of the pharyngeal system via regulation of endoderm expansion.",
"type": "article-journal",
- "doi": "10.1007/s12035-014-9084-z",
+ "doi": "10.1242/dev.02018",
"authors": [
- ["Wentao", "Hu"],
- ["Yongpei", "He"],
- ["Yongjie", "Xiong"],
- ["Hong", "Lu"],
- ["Hong", "Chen"],
- ["Limin", "Hou"],
- ["Zhandong", "Qiu"],
- ["Yu", "Fang"],
- ["Suming", "Zhang"]
+ ["Huansheng", "Xu"],
+ ["Fabiana", "Cerrato"],
+ ["Antonio", "Baldini"]
],
- "publisher": "Molecular neurobiology",
- "issn": "1559-1182",
- "date": "2015-02-10",
- "abstract": "Induced pluripotent stem cells (iPSCs) generated from patient-derived somatic cells provides the opportunity for model development in order to study patient-specific disease states with the potential for drug discovery. However, use of lentivirus and exposure of iPSCs to animal-derived products limit their therapeutic utility and affect lineage differentiation and subsequent downstream functionality of iPSC derivatives. Within the context of this study, we describe a simple and practical protocol enabling the efficient reprogramming of terminally differentiated adult fibroblasts into integration-free human iPSCs (hiPSCs) using a combination of episomal plasmids with small molecules (SMs). Using this approach, there was a 10-fold increase in reprogramming efficiency over single plasmid vector-based methods. We obtained approximately 100 iPSCs colonies from 1\u2009\u00d7\u200910(5) human adult dermal fibroblasts (HADFs) and achieved approximately 0.1% reprogramming efficiencies. Concurrently, we developed a highly conducive culture system using xeno-free media and human vitronectin. The resulting hiPSCs were free of DNA integration and had completely lost episomal vectors, maintained long-term self-renewal, featured a normal karyotype, expressed pluripotent stem cell markers, and possessed the capability of differentiating into components of all three germ layers in vivo. Finally, we demonstrate that the integration-free hiPSCs could be differentiated into motor neurons under xeno-free culture conditions. This induction method will promote the derivation of patient-specific integration-free and xeno-free iPSCs and improve the strategy for motor neuron derivation. Our approach provides a useful tool for human disease models, drug screen, and clinical applications.",
+ "publisher": "Development (Cambridge, England)",
+ "issn": "0950-1991",
+ "date": "2005-09-01",
+ "abstract": "The definition of time-specific requirements for a developmental gene can pinpoint the processes within which the gene is involved and can reveal potential late functions in structures and organs that fail to develop in germline mutants. Here, we show the first systematic time-course deletion, in parallel with timed cell fate mapping, of a developmentally crucial gene, Tbx1, during mouse embryogenesis. Tbx1 mouse mutants model DiGeorge syndrome, a disorder of pharyngeal and cardiovascular development. Results revealed different time requirements for the development of individual structures, as well as multiple and time-distinct roles during the development of the same organ or system. We also show that Tbx1 is required throughout pharyngeal segmentation for the regulation of endoderm expansion, thus this is the first gene implicated directly in this process. A genetic-based blueprint of crucial developmental times for organs and systems should be a valuable asset for our understanding of birth defect pathogenesis.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25663198"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16141220"
},
{
- "id": "pmid:15148657",
+ "id": "pmid:10440825",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/15148657",
- "title": "Uncommon deletions of the Smith-Magenis syndrome region can be recurrent when alternate low-copy repeats act as homologous recombination substrates.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/10440825",
+ "title": "Patient with a 22q11.2 deletion with no overlap of the minimal DiGeorge syndrome critical region (MDGCR).",
"type": "article-journal",
- "doi": "10.1086/422016",
+ "doi": "",
"authors": [
- ["Christine J", "Shaw"],
- ["Marjorie A", "Withers"],
- ["James R", "Lupski"]
+ ["L", "McQuade"],
+ ["J", "Christodoulou"],
+ ["M", "Budarf"],
+ ["R", "Sachdev"],
+ ["M", "Wilson"],
+ ["B", "Emanuel"],
+ ["A", "Colley"]
],
- "publisher": "American journal of human genetics",
- "issn": "0002-9297",
- "date": "2004-05-13",
- "abstract": "Several homologous recombination \"hotspots,\" or sites of positional preference for strand exchanges, associated with recurrent deletions and duplications have been reported within large low-copy repeats (LCRs). Recently, such a hotspot was identified in patients with the Smith-Magenis syndrome (SMS) common deletion of approximately 4 Mb or a reciprocal duplication within the KER gene cluster of the SMS-REP LCRs, in which 50% of analyzed strand exchanges resulting in deletion and 23% of those resulting in duplication occurred. Here, we report an additional recombination hotspot within LCR17pA and LCR17pD, which serve as alternative substrates for nonallelic homologous recombination that results in large (approximately 5 Mb) deletions of 17p11.2, which include the SMS region. Using polymerase-chain-reaction mapping of somatic cell hybrid lines, we refined the breakpoints of six deletions within these LCRs. Sequence analysis of the recombinant junctions revealed that all six strand exchanges occurred within a 524-bp interval, and four of them occurred within an AluSq/x element. This interval represents only 0.5% of the 124-kb stretch of 98.6% sequence identity between LCR17pA and LCR17pD. A search for potentially stimulating sequence motifs revealed short AT-rich segments flanking the recombination hotspot. Our findings indicate that alternative LCRs can mediate rearrangements, resulting in haploinsufficiency of the SMS critical region, and reimplicate homologous recombination as a major mechanism for genomic disorders.",
+ "publisher": "American journal of medical genetics",
+ "issn": "0148-7299",
+ "date": "1999-09-03",
+ "abstract": "The apparent lack of genotype/phenotype correlation in patients with the DiGeorge anomaly and velocardiofacial syndrome (DGA/VCFS; the \"22q11 deletion syndrome\") indicates a complex genetic condition. Most cases, whatever the phenotype, have a 1.5-3 Mb chromosomal deletion that includes the minimal DiGeorge critical region (MDGCR). Another potential critical region on 22q11 has been suggested based on two patients with distal deletions outside the MDGCR. We report on a patient with a VCFS phenotype who has a deletion, mapped by short tandem repeat polymorphic loci and fluorescence in situ hybridization analysis, distal to and not overlapping the MDGCR. This patient is deleted for several genes, including the T-box 1 gene (TBX1; a transcription regulator expressed early in embryogenesis) and catechol-O-methyltransferase (COMT; involved in neurotransmitter metabolism). We discuss the role these two genes may play in the clinical phenotype of the patient.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15148657"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10440825"
},
{
- "id": "pmid:11594924",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/11594924",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:11594924']' timed out after 3 seconds"
+ "id": "pmid:40720054",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/40720054",
+ "title": "Long-Range PCR and Nanopore Sequencing Enables High-Throughput Detection of TCF4 Trinucleotide Repeat Expansions in Fuchs Endothelial Corneal Dystrophy.",
+ "type": "article-journal",
+ "doi": "10.1007/s40291-025-00803-8",
+ "authors": [
+ ["Bushra", "Alayed"],
+ ["Salina", "Siddiqui"],
+ ["Seema", "Anand"],
+ ["Chris F", "Inglehearn"],
+ ["Christopher M", "Watson"],
+ ["Manir", "Ali"]
+ ],
+ "publisher": "Molecular diagnosis & therapy",
+ "issn": "1179-2000",
+ "date": "2025-07-28",
+ "abstract": "Trinucleotide repeat expansion in CTG18.1, in intron 2 of TCF4 (MIM *602272, #613267), is the main cause of Fuchs endothelial corneal dystrophy (FECD), accounting for around 75% of cases in Caucasians. CTG18.1 repeat expansion has typically been detected in peripheral blood genomic DNA by Southern blotting or short tandem repeat polymerase chain reaction (STR-PCR) combined with triplet-repeat primed PCR (TP-PCR) if needed. However both methods estimate the size of the expanded repeat relative to a size standard, and the former requires microgram amounts of DNA. To support the development of therapies, a high-throughput screening approach for repeat expansions in FECD is required. Here, we present a sensitive assay using long-range PCR and nanopore sequencing of genomic DNA to accurately resolve the CTG18.1 repeat.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40720054"
},
{
- "id": "pmid:8817239",
+ "id": "pmid:39288343",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/8817239",
- "title": "Nuclear protein binding and functional activity of a variant insulin gene found in non-insulin-dependent diabetes mellitus.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/39288343",
+ "title": "Change in Visual Acuity of Patients With Fuchs Endothelial Corneal Dystrophy Over 1 Year.",
"type": "article-journal",
- "doi": "10.1055/s-0029-1211446",
+ "doi": "10.1097/ico.0000000000003590",
"authors": [
- ["N", "Yildiz"],
- ["T", "Diedrich"],
- ["W", "Knepel"]
+ ["Oliver", "Dorado-Cortez"],
+ ["Emmanuel", "Crouzet"],
+ ["Marie Caroline", "Trone"],
+ ["Philippe", "Gain"],
+ ["Zhiguo", "He"],
+ ["Hanielle", "Vaitinadapoule"],
+ ["Marielle", "Mentek"],
+ ["Fr\u00e9d\u00e9ric", "Mascarelli"],
+ ["Sylvain", "Poinard"],
+ ["Mari", "Yasunaga"],
+ ["Go", "Nishiuchi"],
+ ["Noriko", "Koizumi"],
+ ["Naoki", "Okumura"],
+ ["Gilles", "Thuret"]
],
- "publisher": "Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association",
- "issn": "0947-7349",
- "date": "1996-01-01",
- "abstract": "In a subset of patients with non-insulin-dependent diabetes mellitus an 8-base pair (bp) repeat was found from -322 to -315 in the 5'-flanking region of the insulin gene. This 8-bp repeat is inserted into a sequence that is highly homologous to a sequence motif, called PISCES (pancreatic islet cell-specific enhancer sequences), found within cell-specific enhancer elements of the rat insulin I (Ins-E1, from -332 to -285), rat glucagon (Glu-G3) and rat somatostatin (SMS-UE) genes. The PISCES motif confers pancreatic islet-specific activity and is recognized by an islet-specific transcription factor (PISCES-BP). The consequences on functional activity and on protein binding of the 8-bp repeat sequence in the human insulin promoter was investigated. When fused to a reporter gene and transiently transfected into an insulin-producing islet cell line, the 8-bp repeat decreased basal transcriptional activity of the human insulin promoter (from -366 to +42) whereas the induction of promoter activity by cAMP was unaffected. The isolated rat Ins-E1 element was sufficient to confer basal transcriptional activity to a minimal promoter; the corresponding fragments of the normal and variant human insulin genes (from -329 to -288), however, were not. Using nuclear extracts in an electrophoretic mobility shift assay, it was found that PISCES-BP recognizes rat Ins-E1, but PISCES-BP binding to the corresponding normal and variant human insulin promoter fragments was not detectable and weak, respectively. However, a nuclear protein was found that binds to the variant but not normal human sequence. These data suggest that the 8-bp repeat in the variant human insulin promoter found in patients with non-insulin-dependent diabetes mellitus allows the binding of a nuclear protein that interferes with promoter function.",
+ "publisher": "Cornea",
+ "issn": "1536-4798",
+ "date": "2024-07-09",
+ "abstract": "To determine whether the clinical and paraclinical course of Fuchs endothelial corneal dystrophy (FECD) over 1 year is related to the extent of triplet repetition in the transcription factor 4 (TCF4) gene.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8817239"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39288343"
},
{
- "id": "pmid:31483537",
+ "id": "pmid:37204786",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/31483537",
- "title": "Intronic (TTTGA)",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/37204786",
+ "title": "The TCF4 Trinucleotide Repeat Expansion of Fuchs' Endothelial Corneal Dystrophy: Implications for the Anterior Segment of the Eye.",
"type": "article-journal",
- "doi": "10.1002/mds.27832",
+ "doi": "10.1167/iovs.64.5.16",
"authors": [
- ["Zhidong", "Cen"],
- ["You", "Chen"],
- ["Dehao", "Yang"],
- ["Qingchen", "Zhu"],
- ["Si", "Chen"],
- ["Xinhui", "Chen"],
- ["Bo", "Wang"],
- ["Fei", "Xie"],
- ["Zhiyuan", "Ouyang"],
- ["Zhengwen", "Jiang"],
- ["Aisi", "Fu"],
- ["Ben", "Hu"],
- ["Houmin", "Yin"],
- ["Xia", "Qiu"],
- ["Feng", "Yu"],
- ["Xiaoping", "Du"],
- ["Weicheng", "Hao"],
- ["Yuxi", "Liu"],
- ["Haotian", "Wang"],
- ["Lebo", "Wang"],
- ["Xiafei", "Yu"],
- ["Yichuan", "Xiao"],
- ["Chunyu", "Liu"],
- ["Jianfeng", "Xiao"],
- ["Yongxing", "Zhou"],
- ["Wei", "Yang"],
- ["Baorong", "Zhang"],
- ["Wei", "Luo"]
+ ["Jiaxin", "Hu"],
+ ["Xin", "Gong"],
+ ["Samantha T", "Johnson"],
+ ["David R", "Corey"],
+ ["V Vinod", "Mootha"]
],
- "publisher": "Movement disorders : official journal of the Movement Disorder Society",
- "issn": "1531-8257",
- "date": "2019-09-04",
- "abstract": "Intronic (TTTCA)",
+ "publisher": "Investigative ophthalmology & visual science",
+ "issn": "1552-5783",
+ "date": "2023-05-01",
+ "abstract": "In the United States, 70% of Fuchs' endothelial corneal dystrophy (FECD) cases are caused by an intronic trinucleotide repeat expansion in the TCF4 gene. CUG repeat RNA transcripts from this expansion accumulate as nuclear foci in the corneal endothelium. In this study, we sought to detect foci in other anterior segment cell types and assess their molecular impact.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31483537"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37204786"
},
{
- "id": "pmid:40481300",
+ "id": "pmid:37169279",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/40481300",
- "title": "Comprehensive Characterisation of the RFC1 Repeat in an Australian Cohort.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/37169279",
+ "title": "Dysregulation of DNA repair genes in Fuchs endothelial corneal dystrophy.",
"type": "article-journal",
- "doi": "10.1007/s12311-025-01867-2",
+ "doi": "10.1016/j.exer.2023.109499",
"authors": [
- ["Kayli C", "Davies"],
- ["Haloom", "Rafehi"],
- ["Liam G", "Fearnley"],
- ["Penny", "Snell"],
- ["Greta", "Gillies"],
- ["Tess A", "Field"],
- ["G\u00e1bor M", "Halm\u00e1gyi"],
- ["Kishore R", "Kumar"],
- ["Kate", "Pope"],
- ["Renee", "Smyth"],
- ["Susan E", "Tomlinson"],
- ["Stephen", "Tisch"],
- ["Chi-Chang", "Tang"],
- ["Shaun R D", "Watson"],
- ["Thomas", "Wellings"],
- ["Kathy H C", "Wu"],
- ["David J", "Szmulewicz"],
- ["Martin B", "Delatycki"],
- ["Melanie", "Bahlo"],
- ["Paul J", "Lockhart"]
+ ["Shazia", "Ashraf"],
+ ["Neha", "Deshpande"],
+ ["Shivakumar", "Vasanth"],
+ ["Geetha", "Melangath"],
+ ["Raymond J", "Wong"],
+ ["Yan", "Zhao"],
+ ["Marianne O", "Price"],
+ ["Francis W", "Price"],
+ ["Ula V", "Jurkunas"]
],
- "publisher": "Cerebellum (London, England)",
- "issn": "1473-4230",
- "date": "2025-06-07",
- "abstract": "RFC1-related disease, which includes cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), is a late-onset neurodegenerative disorder primarily caused by biallelic AAGGG",
+ "publisher": "Experimental eye research",
+ "issn": "1096-0007",
+ "date": "2023-05-09",
+ "abstract": "Fuchs Endothelial Corneal Dystrophy (FECD), a late-onset oxidative stress disorder, is the most common cause of corneal endothelial degeneration and is genetically associated with CTG repeat expansion in Transcription Factor 4 (TCF4). We previously reported accumulation of nuclear (nDNA) and mitochondrial (mtDNA) damage in FECD. Specifically, mtDNA damage was a prominent finding in development of disease in the ultraviolet-A (UVA) induced FECD mouse model. We hypothesize that an aberrant DNA repair may contribute to the increased DNA damage seen in FECD. We analyzed differential expression profiles of 84 DNA repair genes by real-time PCR arrays using Human DNA Repair RT-Profiler plates using cDNA extracted from Descemet's membrane-corneal endothelium (DM-CE) obtained from FECD patients with expanded (>40) or non-expanded (<40) intronic CTG repeats in TCF4 gene and from age-matched normal donors. Change in mRNA expression of <0.5- or >2.0-fold in FECD relative to normal was set as cutoff for down- or upregulation. Downregulated mitochondrial genes were further validated using the UVA-based mouse model of FECD. FECD specimens exhibited downregulation of 9 genes and upregulation of 8 genes belonging to the four major DNA repair pathways, namely, base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), and double strand break (DSB) repair, compared to normal donors. MMR gene MSH2 and BER gene POLB were preferentially upregulated in expanded FECD. BER genes LIG3 and NEIL2, DSB repair genes PARP3 and TOP3A, NER gene XPC, and unclassified pathway gene TREX1, were downregulated in both expanded and non-expanded FECD. MtDNA repair genes, Lig3, Neil2, and Top3a, were also downregulated in the UVA-based mouse model of FECD. Our findings identify impaired DNA repair pathways that may play an important role in DNA damage due to oxidative stress as well as genetic predisposition noted in FECD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40481300"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37169279"
},
{
- "id": "pmid:40471691",
+ "id": "pmid:34946867",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/40471691",
- "title": "Chronic idiopathic axonal neuropathy: antibodies, genetics, and beyond.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/34946867",
+ "title": "Should Patients with Kearns-Sayre Syndrome and Corneal Endothelial Failure Be Genotyped for a",
"type": "article-journal",
- "doi": "10.1097/wco.0000000000001387",
+ "doi": "10.3390/genes12121918",
"authors": [
- ["Mehmet Can", "Sari"],
- ["Ahmet", "Hoke"]
+ ["Lubica", "Dudakova"],
+ ["Pavlina", "Skalicka"],
+ ["Alice E", "Davidson"],
+ ["Amanda N", "Sadan"],
+ ["Monika", "Chylova"],
+ ["Helena", "Jahnova"],
+ ["Nicole", "Anteneova"],
+ ["Marketa", "Tesarova"],
+ ["Tomas", "Honzik"],
+ ["Petra", "Liskova"]
],
- "publisher": "Current opinion in neurology",
- "issn": "1473-6551",
- "date": "2025-06-06",
- "abstract": "Chronic idiopathic axonal neuropathy (CIAP) remains a diagnostic challenge, with many cases historically classified as idiopathic due to the absence of identifiable genetic, metabolic, or immune-mediated causes. This review examines recent advancements in understanding CIAP, focusing on novel genetic mutations, autoantibodies, and metabolic pathways that challenge the \"idiopathic\" designation. Specifically, we highlight sorbitol dehydrogenase (SORD) deficiency and replication factor C subunit 1 (RFC1) repeat expansions, and comment on the controversy surrounding autoantibody-associated small fiber neuropathy (SFN).",
+ "publisher": "Genes",
+ "issn": "2073-4425",
+ "date": "2021-11-29",
+ "abstract": "The aim of this study was to describe the ocular phenotype in a case with Kearns-Sayre syndrome (KSS) spectrum and to determine if corneal endothelial cell dysfunction could be attributed to other known distinct genetic causes. Herein, genomic DNA was extracted from blood and exome sequencing was performed. Non-coding gene regions implicated in corneal endothelial dystrophies were screened by Sanger sequencing. In addition, a repeat expansion situated within an intron of",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40471691"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34946867"
},
{
- "id": "pmid:40461673",
+ "id": "pmid:34855896",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/40461673",
- "title": "Impact of the intronic RFC1 expansion size in CANVAS phenotype: an oculomotor study.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/34855896",
+ "title": "Comparison of TCF4 repeat expansion length in corneal endothelium and leukocytes of patients with Fuchs endothelial corneal dystrophy.",
"type": "article-journal",
- "doi": "10.1007/s00415-025-13150-9",
+ "doi": "10.1371/journal.pone.0260837",
"authors": [
- ["Mathieu", "Dupr\u00e9"],
- ["Ruben", "Hermann"],
- ["L\u00e9o", "Vidoni"],
- ["Isabelle", "Quadrio"],
- ["Philippe", "Latour"],
- ["Fabien", "Subtil"],
- ["Caroline", "Froment Tilikete"]
+ ["Eric D", "Wieben"],
+ ["Ross A", "Aleff"],
+ ["Tommy A", "Rinkoski"],
+ ["Keith H", "Baratz"],
+ ["Shubham", "Basu"],
+ ["Sanjay V", "Patel"],
+ ["Leo J", "Maguire"],
+ ["Michael P", "Fautsch"]
],
- "publisher": "Journal of neurology",
- "issn": "1432-1459",
- "date": "2025-06-03",
- "abstract": "The identification of the RFC1 homozygous intronic expansion in cerebellar ataxia neuropathy and vestibular areflexia syndrome (CANVAS) highlighted that genetically determined CANVAS patients exhibit a wide range of clinical presentations and natural course. Previous studies suggested a link between disease severity and the size of the intronic expansion. The aim of our study was to obtain quantitative data related to vestibular and cerebellar impairments using oculomotor recordings to provide further evidence of a link between RFC1 intronic expansion size and the phenotype. This study recruited 26 genetically determined CANVAS patients in whom the size of the pathological intronic expansion was measured on both alleles. In addition to clinical data, we also recorded the Overall Neuropathy Limitation Scale (ONLS) and conducted objective oculomotor testing. According to the median expansion length on one allele, the patients were divided in a longer intronic repeat subgroup and a shorter intronic repeat subgroup. Given the homozygous nature of this disease, this analysis was carried out for the smallest and for the longest allele. We found for the smallest allele that vestibular deficit and cerebellar impairment were significantly more frequent and mean ONLS, smooth pursuit, pendular visually enhanced vestibulo-ocular reflex, and head impulse vestibulo-ocular reflex gains were significantly more impaired in the subgroup of patients with the long intronic repeat. This work provides objective evidence for a functional impact of the pathological intronic expansion size in CANVAS and highlights the interest of oculomotor assessment in research and clinical practice both for diagnostic and potentially prognostic purposes.",
+ "publisher": "PloS one",
+ "issn": "1932-6203",
+ "date": "2021-12-02",
+ "abstract": "Expansion of CTG trinucleotide repeats (TNR) in the transcription factor 4 (TCF4) gene is highly associated with Fuchs Endothelial Corneal Dystrophy (FECD). Due to limitations in the availability of DNA from diseased corneal endothelium, sizing of CTG repeats in FECD patients has typically been determined using DNA samples isolated from peripheral blood leukocytes. However, it is non-feasible to extract enough DNA from surgically isolated FECD corneal endothelial tissue to determine repeat length based on current technology. To circumvent this issue, total RNA was isolated from FECD corneal endothelium and sequenced using long-read sequencing. Southern blotting of DNA samples isolated from primary cultures of corneal endothelium from these same affected individuals was also assessed. Both long read sequencing and Southern blot analysis showed significantly longer CTG TNR expansion (>1000 repeats) in the corneal endothelium from FECD patients than those characterized in leukocytes from the same individuals (<90 repeats). Our findings suggest that the TCF4 CTG repeat expansions in the FECD corneal endothelium are much longer than those found in leukocytes.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40461673"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34855896"
},
{
- "id": "pmid:40313272",
+ "id": "pmid:32934897",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/40313272",
- "title": "Heterozygous and Homozygous",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/32934897",
+ "title": "Trinucleotide Repeat-Targeting dCas9 as a Therapeutic Strategy for Fuchs' Endothelial Corneal Dystrophy.",
"type": "article-journal",
- "doi": "10.1101/2025.04.18.25325809",
+ "doi": "10.1167/tvst.9.9.47",
"authors": [
- ["Zitian", "Tang"],
- ["Sinem S", "Ovunc"],
- ["Elle", "Mehinovic"],
- ["Simone", "Thomas"],
- ["Jenna", "Ulibarri"],
- ["Zefan", "Li"],
- ["Dustin", "Baldridge"],
- ["Carlos", "Cruchaga"],
- ["Matt", "Johnson"],
- ["Jeffrey", "Milbrandt"],
- ["Brian", "Callaghan"],
- ["Ahmet", "H\u00f6ke"],
- ["Peter K", "Todd"],
- ["Sheng Chih", "Jin"]
+ ["Ziye", "Rong"],
+ ["Xin", "Gong"],
+ ["John D", "Hulleman"],
+ ["David R", "Corey"],
+ ["V Vinod", "Mootha"]
],
- "publisher": "medRxiv : the preprint server for health sciences",
- "issn": "",
- "date": "2025-04-23",
- "abstract": "Biallelic intronic AAGGG repeat expansions in",
+ "publisher": "Translational vision science & technology",
+ "issn": "2164-2591",
+ "date": "2020-08-31",
+ "abstract": "Fuchs' endothelial corneal dystrophy (FECD) is the leading indication for corneal transplantation. Seventy percent of cases are caused by an intronic CTG triplet repeat expansion in the",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40313272"
-},
-{
- "id": "pmid:40221271",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/40221271",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:40221271']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32934897"
},
{
- "id": "pmid:40211677",
+ "id": "pmid:32639312",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/40211677",
- "title": "Genetic and Clinical Features of 10 Families With Hereditary Sensory Neuropathies.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/32639312",
+ "title": "Lower Corneal Haze and Aberrations in Descemet Membrane Endothelial Keratoplasty Versus Descemet Stripping Automated Endothelial Keratoplasty in Fellow Eyes for Fuchs Endothelial Corneal Dystrophy.",
"type": "article-journal",
- "doi": "10.1111/jns.70020",
+ "doi": "10.1097/ico.0000000000002416",
"authors": [
- ["Ke", "Xu"],
- ["Zhongzheng", "Li"],
- ["Mengli", "Wang"],
- ["Lei", "Liu"],
- ["Sen", "Zeng"],
- ["Xiaobo", "Li"],
- ["Wanqian", "Cao"],
- ["Shunxiang", "Huang"],
- ["Huadong", "Zhao"],
- ["Yan", "Yang"],
- ["Yongzhi", "Xie"],
- ["Zhengmao", "Hu"],
- ["Beisha", "Tang"],
- ["Ruxu", "Zhang"]
+ ["William H", "Waldrop"],
+ ["Matthew J", "Gillings"],
+ ["Danielle M", "Robertson"],
+ ["W Matthew", "Petroll"],
+ ["V Vinod", "Mootha"]
],
- "publisher": "Journal of the peripheral nervous system : JPNS",
- "issn": "1529-8027",
- "date": "2025-06-01",
- "abstract": "Hereditary sensory neuropathies (HSNs) are a group of genetically and clinically heterogeneous diseases. Our study aims to summarize the genetic and clinical features of HSNs in 10 Chinese families.",
+ "publisher": "Cornea",
+ "issn": "1536-4798",
+ "date": "2020-10-01",
+ "abstract": "To investigate the long-term corneal changes in patients with Fuchs endothelial corneal dystrophy contributing to superior postoperative visual outcomes after Descemet membrane endothelial keratoplasty (DMEK) compared with Descemet stripping automated endothelial keratoplasty (DSAEK).",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40211677"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32639312"
},
{
- "id": "pmid:40204545",
+ "id": "pmid:30733599",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/40204545",
- "title": "Comment on \"Spectrum disorder of RFC1 expansions/CANVAS: Clinical and electrophysiological characterization of a group of 31 patients\".",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30733599",
+ "title": "CRISPR/Cas9-targeted enrichment and long-read sequencing of the Fuchs endothelial corneal dystrophy-associated TCF4 triplet repeat.",
"type": "article-journal",
- "doi": "10.1016/j.clinph.2025.03.037",
+ "doi": "10.1038/s41436-019-0453-x",
"authors": [
- ["Jos\u00e9", "Berciano"],
- ["Antonio", "Garc\u00eda"],
- ["Jon", "Infante"]
+ ["Nathaniel J", "Hafford-Tear"],
+ ["Yu-Chih", "Tsai"],
+ ["Amanda N", "Sadan"],
+ ["Beatriz", "Sanchez-Pintado"],
+ ["Christina", "Zarouchlioti"],
+ ["Geoffrey J", "Maher"],
+ ["Petra", "Liskova"],
+ ["Stephen J", "Tuft"],
+ ["Alison J", "Hardcastle"],
+ ["Tyson A", "Clark"],
+ ["Alice E", "Davidson"]
],
- "publisher": "Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology",
- "issn": "1872-8952",
- "date": "2025-04-05",
- "abstract": "",
+ "publisher": "Genetics in medicine : official journal of the American College of Medical Genetics",
+ "issn": "1530-0366",
+ "date": "2019-02-08",
+ "abstract": "To demonstrate the utility of an amplification-free long-read sequencing method to characterize the Fuchs endothelial corneal dystrophy (FECD)-associated intronic TCF4 triplet repeat (CTG18.1).",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40204545"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30733599"
},
{
- "id": "pmid:39721397",
+ "id": "pmid:29325021",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/39721397",
- "title": "Spectrum disorder of RFC1 expansions/CANVAS: Clinical and electrophysiological characterization of a group of 31 patients.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/29325021",
+ "title": "Oligonucleotides targeting TCF4 triplet repeat expansion inhibit RNA foci and mis-splicing in Fuchs' dystrophy.",
"type": "article-journal",
- "doi": "10.1016/j.clinph.2024.12.007",
+ "doi": "10.1093/hmg/ddy018",
"authors": [
- ["Elena", "Lainez"],
- ["Daniel", "S\u00e1nchez-Tejerina"],
- ["Paula", "Fern\u00e1ndez Alvarez"],
- ["Margarida", "Gratac\u00f2s-Vi\u00f1ola"],
- ["Jos\u00e9 Luis", "Seoane"],
- ["Daniela Isabel", "Santa-Cruz"],
- ["Lena", "Verdaguer"],
- ["Ra\u00fal", "Juntas"],
- ["Arnau", "Llaurad\u00f3"],
- ["Javier", "Sotoca"],
- ["Maria", "Salvado"],
- ["Elena", "Garc\u00eda Arumi"],
- ["N\u00faria", "Raguer"]
+ ["Jiaxin", "Hu"],
+ ["Ziye", "Rong"],
+ ["Xin", "Gong"],
+ ["Zhengyang", "Zhou"],
+ ["Vivek K", "Sharma"],
+ ["Chao", "Xing"],
+ ["Jonathan K", "Watts"],
+ ["David R", "Corey"],
+ ["V Vinod", "Mootha"]
],
- "publisher": "Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology",
- "issn": "1872-8952",
- "date": "2024-12-19",
- "abstract": "Biallelic expansion of the pentanucleotide AAGGG in the RFC1- gene is associated with cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). This study aimed to comprehensively characterise this condition by conducting an in-depth neurophysiological examination of afflicted patients.",
+ "publisher": "Human molecular genetics",
+ "issn": "1460-2083",
+ "date": "2018-03-15",
+ "abstract": "Fuchs' endothelial corneal dystrophy (FECD) is the most common repeat expansion disorder. FECD impacts 4% of U.S. population and is the leading indication for corneal transplantation. Most cases are caused by an expanded intronic CUG tract in the TCF4 gene that forms nuclear foci, sequesters splicing factors and impairs splicing. We investigated the sense and antisense RNA landscape at the FECD gene and find that the sense-expanded repeat transcript is the predominant species in patient corneas. In patient tissue, sense foci number were negatively correlated with age and showed no correlation with sex. Each endothelial cell has \u223c2 sense foci and each foci is single RNA molecule. We designed antisense oligonucleotides (ASOs) to target the mutant-repetitive RNA and demonstrated potent inhibition of foci in patient-derived cells. Ex vivo treatment of FECD human corneas effectively inhibits foci and reverses pathological changes in splicing. FECD has the potential to be a model for treating many trinucleotide repeat diseases and targeting the TCF4 expansion with ASOs represents a promising therapeutic strategy to prevent and treat FECD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39721397"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29325021"
},
{
- "id": "pmid:39543176",
+ "id": "pmid:29196769",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/39543176",
- "title": "Elucidating the pathobiology of Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome (CANVAS) with its expanded RNA structure formation and proteinopathy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/29196769",
+ "title": "CTG18.1 Expansion in TCF4 Among African Americans With Fuchs' Corneal Dystrophy.",
"type": "article-journal",
- "doi": "10.1038/s41598-024-78947-6",
+ "doi": "10.1167/iovs.17-21661",
"authors": [
- ["Krishna", "Singh"],
- ["Sakshi", "Shukla"],
- ["Uma", "Shankar"],
- ["Neha", "Jain"],
- ["Rishav", "Nag"],
- ["Kumari Aditi", "Pramod"],
- ["Amit", "Kumar"]
+ ["Allen O", "Eghrari"],
+ ["Sina", "Vahedi"],
+ ["Natalie A", "Afshari"],
+ ["S Amer", "Riazuddin"],
+ ["John D", "Gottsch"]
],
- "publisher": "Scientific reports",
- "issn": "2045-2322",
- "date": "2024-11-14",
- "abstract": "Numerous neurological disorders are linked to sequences rich in guanine repeats found in introns, exons, and regulatory regions of genes. These sequences have been observed to form stable G-quadruplex (GQ) structures both\u00a0in vitro\u00a0and in vitro.\u00a0Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome (CANVAS), a slowly progressive neurodegenerative disorder, is associated with the biallelic expansion of (AAGGG)",
+ "publisher": "Investigative ophthalmology & visual science",
+ "issn": "1552-5783",
+ "date": "2017-12-01",
+ "abstract": "Studies of Fuchs' dystrophy have largely focused on individuals of European origin. Characterization of disease among African Americans is required to ensure prognostic factors and therapeutic approaches are applicable across diverse patient populations.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39543176"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29196769"
},
{
- "id": "pmid:39507594",
+ "id": "pmid:26401622",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/39507594",
- "title": "Early Peripheral Nerve Involvement at the Time of Coughing in Patients With",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26401622",
+ "title": "Correlation of Severity of Fuchs Endothelial Corneal Dystrophy With Triplet Repeat Expansion in TCF4.",
"type": "article-journal",
- "doi": "10.1212/nxg.0000000000200166",
+ "doi": "10.1001/jamaophthalmol.2015.3430",
"authors": [
- ["Simon", "Frachet"],
- ["Pauline", "Chazelas"],
- ["Laurent", "Magy"],
- ["Pascal", "Cintas"],
- ["Danielle", "Brouqui\u00e8res"],
- ["Pierre", "Girardie"],
- ["Louise", "Espagno"],
- ["Boris", "Melloni"],
- ["Laurent", "Guilleminault"],
- ["Anne-Sophie", "Lia"]
+ ["Ahmed Z", "Soliman"],
+ ["Chao", "Xing"],
+ ["Salma H", "Radwan"],
+ ["Xin", "Gong"],
+ ["V Vinod", "Mootha"]
],
- "publisher": "Neurology. Genetics",
- "issn": "2376-7839",
- "date": "2024-07-19",
- "abstract": "Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome results from variations in",
+ "publisher": "JAMA ophthalmology",
+ "issn": "2168-6173",
+ "date": "2015-12-01",
+ "abstract": "The CTG18.1 triplet repeat expansion in TCF4 has recently been found to be a common functional variant contributing significant risk to the development of Fuchs endothelial corneal dystrophy (FECD) in Eurasian populations.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39507594"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26401622"
},
{
- "id": "pmid:39416949",
+ "id": "pmid:26218914",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/39416949",
- "title": "Case report: Neuroacanthocytosis associated with novel variants in the",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26218914",
+ "title": "Trinucleotide Repeat Expansion in the TCF4 Gene in Fuchs' Endothelial Corneal Dystrophy in Japanese.",
"type": "article-journal",
- "doi": "10.3389/fnins.2024.1409366",
+ "doi": "10.1167/iovs.15-17082",
"authors": [
- ["Martin", "Paucar"],
- ["Josephine", "Wincent"],
- ["Charlotta", "Rubin"],
- ["Kevin", "Peikert"],
- ["Josefin", "Kyhle"],
- ["Stellan", "Herteg\u00e5rd"],
- ["Riita", "M\u00f6ller"],
- ["Soheir", "Beshara"],
- ["Per", "Svenningsson"]
+ ["Masakazu", "Nakano"],
+ ["Naoki", "Okumura"],
+ ["Hiroko", "Nakagawa"],
+ ["Noriko", "Koizumi"],
+ ["Yoko", "Ikeda"],
+ ["Morio", "Ueno"],
+ ["Kengo", "Yoshii"],
+ ["Hiroko", "Adachi"],
+ ["Ross A", "Aleff"],
+ ["Malinda L", "Butz"],
+ ["W Edward", "Highsmith"],
+ ["Kei", "Tashiro"],
+ ["Eric D", "Wieben"],
+ ["Shigeru", "Kinoshita"],
+ ["Keith H", "Baratz"]
],
- "publisher": "Frontiers in neuroscience",
- "issn": "1662-4548",
- "date": "2024-10-02",
- "abstract": "The diseases historically known as neuroacanthocytosis (NA) conditions include",
+ "publisher": "Investigative ophthalmology & visual science",
+ "issn": "1552-5783",
+ "date": "2015-07-01",
+ "abstract": "The purpose of this study was to evaluate the association between the intronic expansion of a trinucleotide repeat (TNR) in the TCF4 gene and Fuchs' endothelial corneal dystrophy (FECD) in a Japanese population.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39416949"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26218914"
},
{
- "id": "pmid:39286915",
+ "id": "pmid:25298419",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/39286915",
- "title": "Electrophysiological features of the peripheral neuropathy in patients with pathologic biallelic RFC1 repeat expansions.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25298419",
+ "title": "Transethnic replication of association of CTG18.1 repeat expansion of TCF4 gene with Fuchs' corneal dystrophy in Chinese implies common causal variant.",
"type": "article-journal",
- "doi": "10.1002/mus.28257",
+ "doi": "10.1167/iovs.14-15390",
"authors": [
- ["Claudia", "Calezis"],
- ["Nathalie", "Bonello-Palot"],
- ["Annie", "Verschueren"],
- ["Jean-Philippe", "Azulay"],
- ["Etienne", "Fortanier"],
- ["Aude-Marie", "Grapperon"],
- ["Ludivine", "Kouton"],
- ["Julien", "Gallard"],
- ["Emmanuelle", "Salort-Campana"],
- ["Shahram", "Attarian"],
- ["Emilien", "Delmont"]
+ ["Chao", "Xing"],
+ ["Xin", "Gong"],
+ ["Imran", "Hussain"],
+ ["Chiea-Chuen", "Khor"],
+ ["Donald T H", "Tan"],
+ ["Tin", "Aung"],
+ ["Jodhbir S", "Mehta"],
+ ["Eranga N", "Vithana"],
+ ["V Vinod", "Mootha"]
],
- "publisher": "Muscle & nerve",
- "issn": "1097-4598",
- "date": "2024-09-17",
- "abstract": "Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is caused by RFC1 expansions. Sensory neuronopathy, polyneuropathy, and involvement of motor, autonomic, and cranial nerves have all been described with RFC1 expansions. We aimed to describe the electrodiagnostic features of patients with RFC1 expansions through multimodal electrophysiological investigations.",
+ "publisher": "Investigative ophthalmology & visual science",
+ "issn": "1552-5783",
+ "date": "2014-10-08",
+ "abstract": "To test the association between the CTG18.1 trinucleotide repeat expansion of TCF4 gene and Fuchs' endothelial corneal dystrophy (FECD) in a Chinese population.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39286915"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25298419"
},
{
- "id": "pmid:39231235",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/39231235",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:39231235']' timed out after 3 seconds"
+ "id": "pmid:24255041",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/24255041",
+ "title": "Association and familial segregation of CTG18.1 trinucleotide repeat expansion of TCF4 gene in Fuchs' endothelial corneal dystrophy.",
+ "type": "article-journal",
+ "doi": "10.1167/iovs.13-12611",
+ "authors": [
+ ["V Vinod", "Mootha"],
+ ["Xin", "Gong"],
+ ["Hung-Chih", "Ku"],
+ ["Chao", "Xing"]
+ ],
+ "publisher": "Investigative ophthalmology & visual science",
+ "issn": "1552-5783",
+ "date": "2014-01-02",
+ "abstract": "We tested the association between two intronic polymorphisms (CTG18.1 and rs613872) in TCF4 and Fuchs' endothelial corneal dystrophy (FECD), and analyzed their segregation patterns in families.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24255041"
},
{
- "id": "pmid:39076534",
+ "id": "pmid:15368101",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/39076534",
- "title": "Cerebellar ataxia, neuropathy and vestibular areflexia syndrome: a neurogenic cough prototype.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15368101",
+ "title": "SMARCA2 and THAP11: potential candidates for polyglutamine disorders as evidenced from polymorphism and protein-folding simulation studies.",
"type": "article-journal",
- "doi": "10.1183/23120541.00024-2024",
+ "doi": "10.1007/s10038-004-0194-8",
"authors": [
- ["Laurent", "Guilleminault"],
- ["Stuart B", "Mazzone"],
- ["Pauline", "Chazelas"],
- ["Simon", "Frachet"],
- ["Anne-Sophie", "Lia"],
- ["Laurent", "Magy"]
+ ["Neeraj", "Pandey"],
+ ["Uma", "Mittal"],
+ ["Achal K", "Srivastava"],
+ ["Mitali", "Mukerji"]
],
- "publisher": "ERJ open research",
- "issn": "2312-0541",
- "date": "2024-07-29",
- "abstract": "Chronic cough is a frequent disorder that is defined by cough of more than 8\u2005weeks duration. Despite extensive investigation, some patients exhibit no aetiology and others do not respond to specific treatments directed against apparent causes of cough. Such patients are identified as having unexplained or refractory chronic cough. Recently, a high proportion of patients with chronic cough in the context of cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) was highlighted. CANVAS is a rare neurological disorder with a biallelic variation in the replication factor C subunit 1 (",
+ "publisher": "Journal of human genetics",
+ "issn": "1434-5161",
+ "date": "2004-09-10",
+ "abstract": "CAG repeat expansion is the cause of an ever-increasing list of neurodegenerative disorders, especially hereditary ataxias. However, genes responsible for 10-50% of the clinically diagnosed ataxias are still unidentified in different populations. Traditional linkage and repeat expansion-detection based methods complemented with human genome sequence and expression information can now accelerate the pace of identification of putative disease candidates. We have analyzed two CAG repeat containing loci, human SMARCA2 and THAP11, which are expressed in the brain as putative candidates for SCAs, using computational as well as polymorphism scanning approaches. Both loci exhibited features characteristic of genes associated with repeat disorders. These loci are polymorphic with respect to size and interruption pattern in the Indian population. Furthermore, computational analysis of glutamine-stretch embedded domains in the respective proteins predicted these regions to be \"natively unfolded\" beyond a threshold of 40 glutamines. Comparative genome analysis suggested a stabilizing influence of CAA interspersions in repeat tract in THAP11 but not in SMARCA2. Although repeat expansion could not be detected within these genes in unidentified ataxia patients reported in India, we suggest that these loci be screened in other populations, as there is a wide heterogeneity in the prevalence of these disorders in different populations.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39076534"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15368101"
},
{
- "id": "pmid:38978724",
+ "id": "pmid:38411001",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/38978724",
- "title": "Pathologic",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38411001",
+ "title": "Real-time",
"type": "article-journal",
- "doi": "10.1093/braincomms/fcae163",
+ "doi": "10.1039/d3an02107f",
"authors": [
- ["Sara", "Nagy"],
- ["Aisling", "Carr"],
- ["Magdalena", "Mroczek"],
- ["Simon", "Rinaldi"],
- ["Riccardo", "Curro"],
- ["Natalia", "Dominik"],
- ["Nicole", "Japzon"],
- ["Francesca", "Magrinelli"],
- ["Michael P", "Lunn"],
- ["Hadi", "Manji"],
- ["Mary M", "Reilly"],
- ["Andrea", "Cortese"],
- ["Henry", "Houlden"]
+ ["Jiejie", "Guang"],
+ ["Shan", "Wang"],
+ ["Bingyuan", "Fan"],
+ ["Ziyao", "Yu"],
+ ["Yahui", "Gao"],
+ ["Jinru", "Pan"],
+ ["Junting", "Xi"],
+ ["Wei", "Meng"],
+ ["Fang", "Hu"]
],
- "publisher": "Brain communications",
- "issn": "2632-1297",
- "date": "2024-06-03",
- "abstract": "Biallelic expansions of the AAGGG repeat in the replication factor C subunit 1 (",
+ "publisher": "The Analyst",
+ "issn": "1364-5528",
+ "date": "2024-03-25",
+ "abstract": "A biosensor that can detect biomarkers accurately, quickly, and conveniently is important for the diagnosis of various diseases. However, most of the existing detection methods require sample extraction, which makes it difficult to detect and image intracellular molecules or to detect two different types of biomarkers simultaneously. In this study, we constructed a DNA tetrahedral nanoprobe (DTP) capable of detecting both miR378 and telomerase, both of which are tumor markers. In the presence of miR378, FAM on the molecular beacon of DTP fluoresced",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38978724"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38411001"
},
{
- "id": "pmid:38916676",
+ "id": "pmid:38134936",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/38916676",
- "title": "Analysis and occurrence of biallelic pathogenic repeat expansions in RFC1 in a German cohort of patients with a main clinical phenotype of motor neuron disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38134936",
+ "title": "Immune determinants of CAR-T cell expansion in solid tumor patients receiving GD2 CAR-T cell therapy.",
"type": "article-journal",
- "doi": "10.1007/s00415-024-12519-6",
+ "doi": "10.1016/j.ccell.2023.11.011",
"authors": [
- ["Annalisa", "Schaub"],
- ["Hannes", "Erdmann"],
- ["Veronika", "Scholz"],
- ["Manuela", "Timmer"],
- ["Isabell", "Cordts"],
- ["Rene", "G\u00fcnther"],
- ["Peter", "Reilich"],
- ["Angela", "Abicht"],
- ["Florian", "Sch\u00f6berl"]
+ ["Sabina", "Kaczanowska"],
+ ["Tara", "Murty"],
+ ["Ahmad", "Alimadadi"],
+ ["Cristina F", "Contreras"],
+ ["Caroline", "Duault"],
+ ["Priyanka B", "Subrahmanyam"],
+ ["Warren", "Reynolds"],
+ ["Norma A", "Gutierrez"],
+ ["Reema", "Baskar"],
+ ["Catherine J", "Wu"],
+ ["Franziska", "Michor"],
+ ["Jennifer", "Altreuter"],
+ ["Yang", "Liu"],
+ ["Aashna", "Jhaveri"],
+ ["Vandon", "Duong"],
+ ["Hima", "Anbunathan"],
+ ["Claire", "Ong"],
+ ["Hua", "Zhang"],
+ ["Radim", "Moravec"],
+ ["Joyce", "Yu"],
+ ["Roshni", "Biswas"],
+ ["Stephen", "Van Nostrand"],
+ ["James", "Lindsay"],
+ ["Mina", "Pichavant"],
+ ["Elena", "Sotillo"],
+ ["Donna", "Bernstein"],
+ ["Amanda", "Carbonell"],
+ ["Joanne", "Derdak"],
+ ["Jacquelyn", "Klicka-Skeels"],
+ ["Julia E", "Segal"],
+ ["Eva", "Dombi"],
+ ["Stephanie A", "Harmon"],
+ ["Baris", "Turkbey"],
+ ["Bita", "Sahaf"],
+ ["Sean", "Bendall"],
+ ["Holden", "Maecker"],
+ ["Steven L", "Highfill"],
+ ["David", "Stroncek"],
+ ["John", "Glod"],
+ ["Melinda", "Merchant"],
+ ["Catherine C", "Hedrick"],
+ ["Crystal L", "Mackall"],
+ ["Sneha", "Ramakrishna"],
+ ["Rosandra N", "Kaplan"]
],
- "publisher": "Journal of neurology",
- "issn": "1432-1459",
- "date": "2024-06-25",
- "abstract": "Biallelic pathogenic repeat expansions in RFC1 were recently identified as molecular origin of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) as well as of one of the most common causes of adult-onset ataxia. In the meantime, the phenotypic spectrum has expanded massively and now includes mimics of multiple system atrophy or parkinsonism. After identifying a patient with a clinical diagnosis of amyotrophic lateral sclerosis (ALS) as a carrier of biallelic pathogenic repeat expansions in RFC1, we studied a cohort of 106 additional patients with a clinical main phenotype of motor neuron disease (MND) to analyze whether such repeat expansions are more common in MND patients. Indeed, two additional MND patients (one also with ALS and one with primary lateral sclerosis/PLS) have been identified as carrier of biallelic pathogenic repeat expansions in RFC1 in the absence of another genetic alteration explaining the phenotype, suggesting motor neuron disease as another extreme phenotype of RFC1 spectrum disorder. Therefore, MND might belong to the expanding phenotypic spectrum of pathogenic RFC1 repeat expansions, particularly in those MND patients with additional features such as sensory and/or autonomic neuropathy, vestibular deficits, or cerebellar signs. By systematically analyzing the RFC1 repeat array using Oxford nanopore technology long-read sequencing, our study highlights the high intra- and interallelic heterogeneity of this locus and allows the identification of the novel repeat motif 'ACAAG'.",
+ "publisher": "Cancer cell",
+ "issn": "1878-3686",
+ "date": "2023-12-21",
+ "abstract": "Chimeric antigen receptor T\u00a0cells (CAR-Ts) have remarkable efficacy in liquid tumors, but limited responses in solid tumors. We conducted a Phase I trial (NCT02107963) of GD2 CAR-Ts (GD2-CAR.OX40.28.z.iC9), demonstrating feasibility and safety of administration in children and young adults with osteosarcoma and neuroblastoma. Since CAR-T efficacy requires adequate CAR-T expansion, patients were grouped into good or poor expanders across dose levels. Patient samples were evaluated by multi-dimensional proteomic, transcriptomic, and epigenetic analyses. T\u00a0cell assessments identified naive T\u00a0cells in pre-treatment apheresis associated with good expansion, and exhausted T\u00a0cells in CAR-T products with poor expansion. Myeloid cell assessment identified CXCR3",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38916676"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38134936"
},
{
- "id": "pmid:38789445",
+ "id": "pmid:34526668",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/38789445",
- "title": "Profiling complex repeat expansions in RFC1 in Parkinson's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/34526668",
+ "title": "Elevated common variant genetic risk for tourette syndrome in a densely-affected pedigree.",
"type": "article-journal",
- "doi": "10.1038/s41531-024-00723-0",
+ "doi": "10.1038/s41380-021-01277-w",
"authors": [
- ["Pilar", "Alvarez Jerez"],
- ["Kensuke", "Daida"],
- ["Abigail", "Miano-Burkhardt"],
- ["Hirotaka", "Iwaki"],
- ["Laksh", "Malik"],
- ["Guillaume", "Cogan"],
- ["Mary B", "Makarious"],
- ["Roisin", "Sullivan"],
- ["Jana", "Vandrovcova"],
- ["Jinhui", "Ding"],
- ["J Raphael", "Gibbs"],
- ["Androo", "Markham"],
- ["Mike A", "Nalls"],
- ["Rupesh K", "Kesharwani"],
- ["Fritz J", "Sedlazeck"],
- ["Bradford", "Casey"],
- ["John", "Hardy"],
- ["Henry", "Houlden"],
- ["Cornelis", "Blauwendraat"],
- ["Andrew B", "Singleton"],
- ["Kimberley J", "Billingsley"]
+ ["Matthew", "Halvorsen"],
+ ["Jin", "Szatkiewicz"],
+ ["Poorva", "Mudgal"],
+ ["Dongmei", "Yu"],
+ ["Ashley E", "Nordsletten"],
+ ["David", "Mataix-Cols"],
+ ["Carol A", "Mathews"],
+ ["Jeremiah M", "Scharf"],
+ ["Manuel", "Mattheisen"],
+ ["Mary M", "Robertson"],
+ ["Andrew", "McQuillin"],
+ ["James J", "Crowley"]
],
- "publisher": "NPJ Parkinson's disease",
- "issn": "2373-8057",
- "date": "2024-05-24",
- "abstract": "A biallelic (AAGGG) expansion in the poly(A) tail of an AluSx3 transposable element within the gene RFC1 is a frequent cause of cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS), and more recently, has been reported as a rare cause of Parkinson's disease (PD) in the Finnish population. Here, we investigate the prevalence of RFC1 (AAGGG) expansions in PD patients of non-Finnish European ancestry in 1609 individuals from the Parkinson's Progression Markers Initiative study. We identified four PD patients carrying the biallelic RFC1 (AAGGG) expansion and did not identify any carriers in controls.",
+ "publisher": "Molecular psychiatry",
+ "issn": "1476-5578",
+ "date": "2021-09-15",
+ "abstract": "Tourette syndrome (TS) is a highly heritable neuropsychiatric disorder with complex patterns of genetic inheritance. Recent genetic findings in TS have highlighted both numerous common variants with small effects and a few rare variants with moderate or large effects. Here we searched for genetic causes of TS in a large, densely-affected British pedigree using a systematic genomic approach. This pedigree spans six generations and includes 122 members, 85 of whom were individually interviewed, and 53 of whom were diagnosed as \"cases\" (consisting of 28 with definite or probable TS, 20 with chronic multiple tics [CMT], and five with obsessive-compulsive behaviors [OCB]). A total of 66 DNA samples were available (25 TS, 15 CMT, 4 OCB cases, and 22 unaffecteds) and all were genotyped using a dense single nucleotide polymorphism (SNP) array to identify shared segments, copy number variants (CNVs), and to calculate genetic risk scores. Eight cases were also whole genome sequenced to test whether any rare variants were shared identical by descent. While we did not identify any notable CNVs, single nucleotide variants, indels or repeat expansions of near-Mendelian effect, the most distinctive feature of this family proved to be an unusually high load of common risk alleles for TS. We found that cases within this family carried a higher load of TS common variant risk similar to that previously found in unrelated TS cases. Thus far, the strongest evidence from genetic data for contribution to TS risk in this family comes from multiple common risk variants rather than one or a few variants of strong effect.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38789445"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34526668"
},
{
- "id": "pmid:38579416",
+ "id": "pmid:34197619",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/38579416",
- "title": "Bilateral vestibulopathy as the initial presentation of CANVAS.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/34197619",
+ "title": "Strand-specific effect of Rad26 and TFIIS in rescuing transcriptional arrest by CAG trinucleotide repeat slip-outs.",
"type": "article-journal",
- "doi": "10.1016/j.jns.2024.122990",
+ "doi": "10.1093/nar/gkab573",
"authors": [
- ["Carlos R", "Gordon"],
- ["Roy", "Zaltzman"],
- ["Dario", "Geisinger"],
- ["Zohar", "Elyoseph"],
- ["Yoav", "Gimmon"]
+ ["Jun", "Xu"],
+ ["Jenny", "Chong"],
+ ["Dong", "Wang"]
],
- "publisher": "Journal of the neurological sciences",
- "issn": "1878-5883",
- "date": "2024-04-02",
- "abstract": "Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a slowly progressing autosomal recessive ataxic disorder linked to an abnormal biallelic intronic (most commonly) AAGGG repeat expansion in the replication factor complex subunit 1 (RFC1). While the clinical diagnosis is relatively straightforward when the three components of the disorder are present, it becomes challenging when only one of the triad (cerebellar ataxia, neuropathy or vestibular areflexia) manifests. Isolated cases of Bilateral Vestibulopathy (BVP) or vestibular areflexia that later developed the other components of CANVAS have not been documented. We report four cases of patients with chronic imbalance and BVP that, after several years, developed cerebellar and neuropathic deficits with positive genetic testing for RFC1. Our report supports the concept that CANVAS should be considered in every patient with BVP of unknown etiology, even without the presence of the other triad components. This is especially important given that about 50% of cases in many BVP series are diagnosed as idiopathic, some of which may be undiagnosed CANVAS.",
+ "publisher": "Nucleic acids research",
+ "issn": "1362-4962",
+ "date": "2021-07-21",
+ "abstract": "Transcription induced CAG repeat instability is associated with fatal neurological disorders. Genetic approaches found transcription-coupled nucleotide excision repair (TC-NER) factor CSB protein and TFIIS play critical roles in modulating the repeat stability. Here, we took advantage of an in vitro reconstituted yeast transcription system to investigate the underlying mechanism of RNA polymerase II (Pol II) transcriptional pausing/stalling by CAG slip-out structures and the functions of TFIIS and Rad26, the yeast ortholog of CSB, in modulating transcriptional arrest. We identified length-dependent and strand-specific mechanisms that account for CAG slip-out induced transcriptional arrest. We found substantial R-loop formation for the distal transcriptional pausing induced by template strand (TS) slip-out, but not non-template strand (NTS) slip-out. In contrast, Pol II backtracking was observed at the proximal transcriptional pausing sites induced by both NTS and TS slip-out blockage. Strikingly, we revealed that Rad26 and TFIIS can stimulate bypass of NTS CAG slip-out, but not TS slip-out induced distal pausing. Our biochemical results provide new insights into understanding the mechanism of CAG slip-out induced transcriptional pausing and functions of transcription factors in modulating transcription-coupled CAG repeat instability, which may pave the way for developing potential strategies for the treatment of repeat sequence associated human diseases.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38579416"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34197619"
},
{
- "id": "pmid:38311638",
+ "id": "pmid:32813677",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/38311638",
- "title": "The impact of folate pathway variants on the outcome of methotrexate therapy in rheumatoid arthritis patients.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/32813677",
+ "title": "Impact of parental origin of X-chromosome on clinical and biochemical profile in Turner syndrome.",
"type": "article-journal",
- "doi": "10.1007/s10067-024-06892-w",
+ "doi": "10.1515/jpem-2020-0104",
"authors": [
- ["Azhar M", "Nomair"],
- ["Abeer", "Abdelati"],
- ["Fatma I", "Dwedar"],
- ["Rehab", "Elnemr"],
- ["Yasmine N", "Kamel"],
- ["Hanan M", "Nomeir"]
+ ["Rakhi", "Malhotra"],
+ ["Rashmi", "Shukla"],
+ ["Madhulika", "Kabra"],
+ ["Yashdeep", "Gupta"],
+ ["Viveka P", "Jyotsna"],
+ ["Rajesh", "Khadgawat"]
],
- "publisher": "Clinical rheumatology",
- "issn": "1434-9949",
- "date": "2024-02-05",
- "abstract": "There are currently no validated criteria that entirely explain or predict response to methotrexate (MTX) treatment in rheumatoid arthritis (RA). We tried to identify the connection between three variants (RFC1 G80A (rs1051266), TYMS 2R/3R (rs34743033), and ATIC C347G (rs2372536)) in the folate pathway of MTX metabolism and the response to MTX monotherapy in a cohort of RA cases.",
+ "publisher": "Journal of pediatric endocrinology & metabolism : JPEM",
+ "issn": "2191-0251",
+ "date": "2020-09-25",
+ "abstract": "Objectives To evaluate if the parental origin of X-chromosome has an impact on the phenotype and biochemical profile in Turner syndrome (TS). Result of the previous studies have been equivocal and could be attributable to the multicentric study design with different experts examining heterogeneous TS population of various ethnic background. Methods A cross-sectional single center study from Northern India. Fifty nine diagnosed subjects of TS and their parents participated in the study. Parental origin of intact X-chromosome was determined using 12 highly polymorphic short tandem repeats (STR) on X-chromosome. For the evaluation of parent-of-origin effects, typical phenotypic traits including congenital malformations, anthropometry, body composition by dual energy X-ray absorptiometry (DXA) and biochemical profile were compared. Clinical stigmata of TS in all subjects were examined by a single expert. Results The intact X-chromosome was of maternal origin (Xm) in 49.1% subjects while 50.9% had paternal origin (Xp). Skeletal anomalies were more common in Xm group, out of which prevalence of short neck and short fourth metatarsal reached statistical significance (p=0.04 and 0.01 respectively). A strong correlation was observed between subject's baseline height standard deviation score (Ht SDS) and paternal height (r=0.593, p<0.001), maternal height (r=0.564, p<0.001) and mid-parental height (MPH) (r=0.372, p=0.047) in Xp group. This effect was not seen in Xm subjects whose baseline Ht SDS showed no significant correlation with maternal height, paternal height or MPH. No differences were detected between the groups with regard to biochemical profile or body composition. Conclusions We speculate that the differences in skeletal anomalies and height correlations between Xm and Xp groups could be due to the modifying effect of epigenetic signature on short stature homeobox (SHOX) gene of Xm. SHOX gene is not modified on Xp thereby explaining the paucity of skeletal changes and height correlations in Xp subjects.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38311638"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32813677"
},
{
- "id": "pmid:38306376",
+ "id": "pmid:32695278",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/38306376",
- "title": "Cerebellar Ataxia With Neuropathy and Vestibular Areflexia Syndrome Due to Replication Factor C Subunit 1 Gene Repeat Expansion.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/32695278",
+ "title": "The Role of",
"type": "article-journal",
- "doi": "10.1097/rlu.0000000000005047",
+ "doi": "",
"authors": [
- ["Mitsuteru", "Tsuchiya"],
- ["Tomoyasu", "Bunai"],
- ["Kazuki", "Watanabe"],
- ["Hirotomo", "Saitsu"],
- ["Satoshi", "Goshima"]
- ],
- "publisher": "Clinical nuclear medicine",
- "issn": "1536-0229",
- "date": "2024-01-15",
- "abstract": "A 56-year-old man was born to consanguineous parents. He experienced slow-progressing sensory disturbances in the upper extremities. T1-weighted images showed cerebellar atrophy. 123I-IMP SPECT revealed reduced cerebral blood flow in the cerebellum. 123I-FP-CIT SPECT showed low uptake of dopamine transporter in the bilateral tail of the striatum. 123I-MIBG scintigraphy shows a decreased heart-to-mediastinum ratio. Flanking polymerase chain reaction suggested biallelic repeat expansion in intron 2 of RFC1, and subsequent repeat-primed polymerase chain reaction revealed ACAGG repeat expansion. Thus, he was diagnosed as cerebellar ataxia with neuropathy and vestibular areflexia syndrome.",
+ ["Mohammad Hadi", "Abbasian"],
+ ["Nafiseh", "Ansarinejad"],
+ ["Bahareh", "Abbasi"],
+ ["Masoud", "Iravani"],
+ ["Tayeb", "Ramim"],
+ ["Fahime", "Hamedi"],
+ ["Ali M", "Ardekani"]
+ ],
+ "publisher": "Avicenna journal of medical biotechnology",
+ "issn": "2008-2835",
+ "date": "2020-01-01",
+ "abstract": "The fluoropyrimidine drug 5-Fluorouracil (5-FU) and the prodrug capecitabine have been extensively used for treatment of many types of cancer including colorectal, gastric, head and neck. Approximately, 10 to 25% of patients suffer from severe fluoropyrimidine-induced toxicity. This may lead to dose reduction and treatment discontinuation. Pharmacogenetics research could be useful for the identification of predictive markers in chemotherapy treatment. The aim of the study was to investigate the role of five genetic polymorphisms within two genes (",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38306376"
-},
-{
- "id": "pmid:38266156",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/38266156",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:38266156']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32695278"
},
{
- "id": "pmid:38193360",
+ "id": "pmid:30464574",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/38193360",
- "title": "Role of the repeat expansion size in predicting age of onset and severity in RFC1 disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30464574",
+ "title": "Influence of MSI and 18q LOH markers on capecitabine adjuvant monotherapy in colon cancer patients.",
"type": "article-journal",
- "doi": "10.1093/brain/awad436",
+ "doi": "10.2147/pgpm.s172467",
"authors": [
- ["Riccardo", "Curr\u00f2"],
- ["Natalia", "Dominik"],
- ["Stefano", "Facchini"],
- ["Elisa", "Vegezzi"],
- ["Roisin", "Sullivan"],
- ["Valentina", "Galassi Deforie"],
- ["Gorka", "Fern\u00e1ndez-Eulate"],
- ["Andreas", "Trasch\u00fctz"],
- ["Salvatore", "Rossi"],
- ["Matteo", "Garibaldi"],
- ["Mariusz", "Kwarciany"],
- ["Franco", "Taroni"],
- ["Alfredo", "Brusco"],
- ["Jean-Marc", "Good"],
- ["Francesca", "Cavalcanti"],
- ["Simon", "Hammans"],
- ["Gianina", "Ravenscroft"],
- ["Richard H", "Roxburgh"],
- ["Ricardo", "Parolin Schnekenberg"],
- ["Bianca", "Rugginini"],
- ["Elena", "Abati"],
- ["Arianna", "Manini"],
- ["Ilaria", "Quartesan"],
- ["Arianna", "Ghia"],
- ["Adolfo", "L\u00f2pez de Muna\u00ecn"],
- ["Fiore", "Manganelli"],
- ["Marina", "Kennerson"],
- ["Filippo Maria", "Santorelli"],
- ["Jon", "Infante"],
- ["Wilson", "Marques"],
- ["Manu", "Jokela"],
- ["Sin\u00e9ad M", "Murphy"],
- ["Paola", "Mandich"],
- ["Gian Maria", "Fabrizi"],
- ["Chiara", "Briani"],
- ["David", "Gosal"],
- ["Davide", "Pareyson"],
- ["Alberto", "Ferrari"],
- ["Ferran", "Prados"],
- ["Tarek", "Yousry"],
- ["Vikram", "Khurana"],
- ["Sheng-Han", "Kuo"],
- ["James", "Miller"],
- ["Claire", "Troakes"],
- ["Zane", "Jaunmuktane"],
- ["Paola", "Giunti"],
- ["Annette", "Hartmann"],
- ["Nazli", "Basak"],
- ["Matthis", "Synofzik"],
- ["Tanya", "Stojkovic"],
- ["Marios", "Hadjivassiliou"],
- ["Mary M", "Reilly"],
- ["Henry", "Houlden"],
- ["Andrea", "Cortese"]
+ ["Nadica", "Matevska-Geshkovska"],
+ ["Marija", "Staninova-Stojovska"],
+ ["Aleksandra", "Kapedanovska-Nestorovska"],
+ ["Natalija", "Petrushevska-Angelovska"],
+ ["Milco", "Panovski"],
+ ["Biljana", "Grozdanovska"],
+ ["Nenad", "Mitreski"],
+ ["Aleksandar", "Dimovski"]
],
- "publisher": "Brain : a journal of neurology",
- "issn": "1460-2156",
- "date": "2024-05-03",
- "abstract": "RFC1 disease, caused by biallelic repeat expansion in RFC1, is clinically heterogeneous in terms of age of onset, disease progression and phenotype. We investigated the role of the repeat size in influencing clinical variables in RFC1 disease. We also assessed the presence and role of meiotic and somatic instability of the repeat. In this study, we identified 553 patients carrying biallelic RFC1 expansions and measured the repeat expansion size in 392 cases. Pearson's coefficient was calculated to assess the correlation between the repeat size and age at disease onset. A Cox model with robust cluster standard errors was adopted to describe the effect of repeat size on age at disease onset, on age at onset of each individual symptoms, and on disease progression. A quasi-Poisson regression model was used to analyse the relationship between phenotype and repeat size. We performed multivariate linear regression to assess the association of the repeat size with the degree of cerebellar atrophy. Meiotic stability was assessed by Southern blotting on first-degree relatives of 27 probands. Finally, somatic instability was investigated by optical genome mapping on cerebellar and frontal cortex and unaffected peripheral tissue from four post-mortem cases. A larger repeat size of both smaller and larger allele was associated with an earlier age at neurological onset [smaller allele hazard ratio (HR) = 2.06, P < 0.001; larger allele HR = 1.53, P < 0.001] and with a higher hazard of developing disabling symptoms, such as dysarthria or dysphagia (smaller allele HR = 3.40, P < 0.001; larger allele HR = 1.71, P = 0.002) or loss of independent walking (smaller allele HR = 2.78, P < 0.001; larger allele HR = 1.60; P < 0.001) earlier in disease course. Patients with more complex phenotypes carried larger expansions [smaller allele: complex neuropathy rate ratio (RR) = 1.30, P = 0.003; cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) RR = 1.34, P < 0.001; larger allele: complex neuropathy RR = 1.33, P = 0.008; CANVAS RR = 1.31, P = 0.009]. Furthermore, larger repeat expansions in the smaller allele were associated with more pronounced cerebellar vermis atrophy (lobules I-V \u03b2 = -1.06, P < 0.001; lobules VI-VII \u03b2 = -0.34, P = 0.005). The repeat did not show significant instability during vertical transmission and across different tissues and brain regions. RFC1 repeat size, particularly of the smaller allele, is one of the determinants of variability in RFC1 disease and represents a key prognostic factor to predict disease onset, phenotype and severity. Assessing the repeat size is warranted as part of the diagnostic test for RFC1 expansion.",
+ "publisher": "Pharmacogenomics and personalized medicine",
+ "issn": "1178-7066",
+ "date": "2018-11-01",
+ "abstract": "The aim of this study was to evaluate whether pretreatment analysis of selected molecular markers can be used for the prediction of disease-free survival (DFS)/overall survival (OS) of capecitabine adjuvant monotherapy in colon cancer patients.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38193360"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30464574"
},
{
- "id": "pmid:38145611",
+ "id": "pmid:29394274",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/38145611",
- "title": "Unraveling the genetic landscape of undiagnosed cerebellar ataxia in Brazilian patients.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/29394274",
+ "title": "XRCC3 Thr241Met and TYMS variable number tandem repeat polymorphisms are associated with time-to-metastasis in colorectal cancer.",
"type": "article-journal",
- "doi": "10.1016/j.parkreldis.2023.105961",
+ "doi": "10.1371/journal.pone.0192316",
"authors": [
- ["Luiz Eduardo", "Novis"],
- ["Shahryar", "Alavi"],
- ["David", "Pellerin"],
- ["Marcus Vinicius", "Della Coleta"],
- ["Salmo", "Raskin"],
- ["Mariana", "Spitz"],
- ["Andrea", "Cortese"],
- ["Henry", "Houlden"],
- ["Helio Afonso", "Teive"]
+ ["Yanjing", "He"],
+ ["Michelle E", "Penney"],
+ ["Amit A", "Negandhi"],
+ ["Patrick S", "Parfrey"],
+ ["Sevtap", "Savas"],
+ ["Yildiz E", "Yilmaz"]
],
- "publisher": "Parkinsonism & related disorders",
- "issn": "1873-5126",
- "date": "2023-12-20",
- "abstract": "Hereditary ataxias (HAs) encompass a diverse and genetically intricate group of rare neurodegenerative disorders, presenting diagnostic challenges. Whole-exome sequencing (WES) has significantly improved diagnostic success. This study aimed to elucidate genetic causes of cerebellar ataxia within a diverse Brazilian cohort.",
+ "publisher": "PloS one",
+ "issn": "1932-6203",
+ "date": "2018-02-02",
+ "abstract": "Metastasis is a major cause of mortality in cancer. Identifying prognostic factors that distinguish patients who will experience metastasis in the short-term and those that will be free of metastasis in the long-term is of particular interest in current medical research. The objective of this study was to examine if select genetic polymorphisms can differentiate colorectal cancer patients based on timing and long-term risk of metastasis.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38145611"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29394274"
},
{
- "id": "pmid:38062616",
+ "id": "pmid:29321350",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/38062616",
- "title": "RNA Foci in Two bi-Allelic RFC1 Expansion Carriers.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/29321350",
+ "title": "Neuro-fuzzy model of homocysteine metabolism.",
"type": "article-journal",
- "doi": "10.1002/ana.26848",
+ "doi": "10.1007/s12041-017-0856-x",
"authors": [
- ["Taishi", "Wada"],
- ["Hiroshi", "Doi"],
- ["Masaki", "Okubo"],
- ["Mikiko", "Tada"],
- ["Naohisa", "Ueda"],
- ["Hidefumi", "Suzuki"],
- ["Wakana", "Tominaga"],
- ["Haruki", "Koike"],
- ["Hiroyasu", "Komiya"],
- ["Shun", "Kubota"],
- ["Shunta", "Hashiguchi"],
- ["Haruko", "Nakamura"],
- ["Keita", "Takahashi"],
- ["Misako", "Kunii"],
- ["Kenichi", "Tanaka"],
- ["Yosuke", "Miyaji"],
- ["Yuichi", "Higashiyama"],
- ["Eriko", "Koshimizu"],
- ["Satoko", "Miyatake"],
- ["Masahisa", "Katsuno"],
- ["Satoshi", "Fujii"],
- ["Hidehisa", "Takahashi"],
- ["Naomichi", "Matsumoto"],
- ["Hideyuki", "Takeuchi"],
- ["Fumiaki", "Tanaka"]
+ ["Shaik Mohammad", "Naushad"],
+ ["Akella Radha", "Rama Devi"],
+ ["Sriraman", "Nivetha"],
+ ["Ganapathy", "Lakshmitha"],
+ ["Alex Balraj", "Stanley"],
+ ["Tajamul", "Hussain"],
+ ["Vijay Kumar", "Kutala"]
],
- "publisher": "Annals of neurology",
- "issn": "1531-8249",
- "date": "2023-12-27",
- "abstract": "Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is a late-onset, autosomal recessive neurodegenerative disorder caused by biallelic AAGGG/ACAGG repeat expansion (AAGGG-exp/ACAGG-exp) in RFC1. The recent identification of patients with CANVAS exhibiting compound heterozygosity for AAGGG-exp and truncating variants supports the loss-of-function of RFC1 in CANVAS patients. We investigated the pathological changes in 2 autopsied patients with CANVAS harboring biallelic ACAGG-exp and AAGGG-exp. RNA fluorescence in situ hybridization of the 2 patients revealed CCTGT- and CCCTT-containing RNA foci, respectively, in neuronal nuclei of tissues with neuronal loss. Our findings suggest that RNA toxicity may be involved in the pathogenesis of CANVAS. ANN NEUROL 2024;95:607-613.",
+ "publisher": "Journal of genetics",
+ "issn": "0973-7731",
+ "date": "2017-12-01",
+ "abstract": "In view of well-documented association of hyperhomocysteinaemia with a wide spectrum of diseases and higher incidence of vitamin deficiencies in Indians, we proposed a mathematical model to forecast the role of demographic and genetic variables in influencing homocysteinemetabolism and investigated the influence of life style modulations in controlling homocysteine levels. Total plasma homocysteine levels were measured in fasting samples using reverse phase HPLC. Multiple linear regression (MLR) and neuro-fuzzy models were developed. The MLR model explained 64% variability in homocysteine, while the neurofuzzy model showed higher accuracy in predicting homocysteine with a mean absolute error of 0.00002 \u03bcmol/L. Methylene tetrahydrofolate reductase (MTHFR) C677T, 5-methyltetrahydrofolate homocysteine methyltransferase (MTR) A2756G and 5- methyltetrahydrofolate homocysteine methyltransferase reductase (MTRR) A66G were shown to be positively associatiated with homocysteine, while nonvegetarian diet, serine hydroxymethyltransferase 1 (SHMT1) C1420T and TYMS 5'-UTR 28 bp tandem repeat exhibited negative association with homocysteine. The protective role of SHMT1 C1420T was attributed to more H-bonding interactions in the mutant modelled compared to the wild type, as shown through in silico analysis. To conclude, polymorphisms in genes regulating remethylation of homocysteine strongly influence homocysteine levels. The restoration of one-carbon homeostasis by SHMT1 C1420T or increased flux of folate towards remethylation due to TYMS 5'-UTR 28 bp tandem repeat or nonvegetarian diet can lower homocysteine levels.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38062616"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29321350"
},
{
- "id": "pmid:38054570",
+ "id": "pmid:28280649",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/38054570",
- "title": "Serum Neurofilament Light Chain in Replication Factor Complex Subunit 1 CANVAS and Disease Spectrum.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/28280649",
+ "title": "First Case of Foot Drop Associated with Capecitabine in a Patient with Thymidylate Synthase Polymorphism.",
"type": "article-journal",
- "doi": "10.1002/mds.29680",
+ "doi": "10.7759/cureus.995",
"authors": [
- ["Ilaria", "Quartesan"],
- ["Elisa", "Vegezzi"],
- ["Riccardo", "Curr\u00f2"],
- ["Amanda", "Heslegrave"],
- ["Chiara", "Pisciotta"],
- ["Pablo", "Iruzubieta"],
- ["Alessandro", "Salvalaggio"],
- ["Gorka", "Fern\u00e1ndez-Eulate"],
- ["Natalia", "Dominik"],
- ["Bianca", "Rugginini"],
- ["Arianna", "Manini"],
- ["Elena", "Abati"],
- ["Stefano", "Facchini"],
- ["Katarina", "Manso"],
- ["Ines", "Albajar"],
- ["Rhiannon", "Laban"],
- ["Alexander M", "Rossor"],
- ["Anna", "Pichiecchio"],
- ["Giuseppe", "Cosentino"],
- ["Paola", "Saveri"],
- ["Ettore", "Salsano"],
- ["Francesca", "Andreetta"],
- ["Enza M", "Valente"],
- ["Henrik", "Zetterberg"],
- ["Paola", "Giunti"],
- ["Tanya", "Stojkovic"],
- ["Chiara", "Briani"],
- ["Adolfo", "L\u00f3pez de Munain"],
- ["Davide", "Pareyson"],
- ["Mary M", "Reilly"],
- ["Henry", "Houlden"],
- ["Cristina", "Tassorelli"],
- ["Andrea", "Cortese"]
+ ["Andrew B", "Wilks"],
+ ["Muhammad W", "Saif"]
],
- "publisher": "Movement disorders : official journal of the Movement Disorder Society",
- "issn": "1531-8257",
- "date": "2023-12-06",
- "abstract": "Biallelic intronic AAGGG repeat expansions in the replication factor complex subunit 1 (RFC1) gene were identified as the leading cause of cerebellar ataxia, neuropathy, vestibular areflexia syndrome. Patients exhibit significant clinical heterogeneity and variable disease course, but no potential biomarker has been identified to date.",
+ "publisher": "Cureus",
+ "issn": "2168-8184",
+ "date": "2017-01-24",
+ "abstract": "Capecitabine, an oral prodrug of 5-FU, has been approved by the FDA for use in patients with breast and colon cancers. In addition, capecitabine is commonly used in patients with other malignancies such as pancreatic, gastroesophageal, and hepatobiliary tract cancers. Though cerebellar toxicity is a rare but well-known side effect of intravenous 5-FU therapy, peripheral neuropathy with capecitabine has only been described in rare cases. In this case report, we describe a 79-year-old patient with locally advanced adenocarcinoma of the pancreas undergoing chemoradiation therapy with capecitabine who developed peripheral sensorimotor neuropathy. To the best of our knowledge, this is the first patient in the literature who was found to have two mutations (2R) of a 28 base-pair tandem repeat in the 5' promoter enhancer region (5'-TSER) on both alleles (2R/2R) of thymidylate synthetase (TYMS) gene, possibly responsible for the neurotoxicity.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38054570"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28280649"
},
{
- "id": "pmid:37892228",
+ "id": "pmid:28074308",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/37892228",
- "title": "Optical Genome Mapping Enables Detection and Accurate Sizing of",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/28074308",
+ "title": "Influence of TS and ABCB1\u00a0gene polymorphisms on survival outcomes of 5\u2011FU-based chemotherapy in a\u00a0Chinese population of advanced gastric cancer patients.",
"type": "article-journal",
- "doi": "10.3390/biom13101546",
- "authors": [
- ["Stefano", "Facchini"],
- ["Natalia", "Dominik"],
- ["Arianna", "Manini"],
- ["Stephanie", "Efthymiou"],
- ["Riccardo", "Curr\u00f2"],
- ["Bianca", "Rugginini"],
- ["Elisa", "Vegezzi"],
- ["Ilaria", "Quartesan"],
- ["Benedetta", "Perrone"],
- ["Shahedah Koya", "Kutty"],
- ["Valentina", "Galassi Deforie"],
- ["Ricardo P", "Schnekenberg"],
- ["Elena", "Abati"],
- ["Anna", "Pichiecchio"],
- ["Enza Maria", "Valente"],
- ["Cristina", "Tassorelli"],
- ["Mary M", "Reilly"],
- ["Henry", "Houlden"],
- ["Enrico", "Bugiardini"],
- ["Andrea", "Cortese"]
+ "doi": "10.1007/s00508-016-1147-x",
+ "authors": [
+ ["Jun", "Chen"],
+ ["Xueming", "Ying"],
+ ["Ling", "Zhang"],
+ ["Xiaojun", "Xiang"],
+ ["Jianping", "Xiong"]
],
- "publisher": "Biomolecules",
- "issn": "2218-273X",
- "date": "2023-10-19",
- "abstract": "A recessive Short Tandem Repeat expansion in",
+ "publisher": "Wiener klinische Wochenschrift",
+ "issn": "1613-7671",
+ "date": "2017-01-10",
+ "abstract": "To investigate the impacts of gene variations on survival outcomes of advanced gastric cancer (AGC) patients treated with 5\u2011fluorouracil (5-FU)-based chemotherapy, we analyzed the associations of 2 indels of the TS gene rs34743033 (double or triple tandem repeats of a\u00a028\u2009bp sequence in 5'-UTR, denoted as 2R or 3R allele) and rs16430 (a\u00a06\u2009bp variation at 1494\u2009bp in 3'-UTR, denoted as ins6 or del6\u00a0allele) and 2 single nucleotide polymorphisms (SNPs) of ABCB1gene rs2032582 in exon\u00a021 and rs1045642 in exon\u00a026, with clinical outcomes after 5\u2011FU treatment. Generally, indels rs34743033 and rs16430 were genotyped by PCR and polyacrylamide gel electrophoresis assay and SNPs rs2032582 and rs1045642 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in 110\u00a0Chinese AGC patients post-chemotherapy. Cox regression analysis was used to analyze the risk factors affecting patient survival. As a\u00a0result, rs34743033, rs1045642 and rs2032582 were shown to be significantly associated with overall survival (P\u00a0< 0.05), and associations between the four polymorphisms with disease-free survival were also observed (P\u00a0< 0.05). Moreover, we found that genotypes rs34743033 3R/2R, rs16430 ins6/del6, rs1045642 CC or CT, and rs2032582\u00a0GG were beneficial predictors of clinical treatment outcome in AGC patients, suggesting some clinical implications in chemotherapy of a\u00a0Chinese population.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37892228"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28074308"
},
{
- "id": "pmid:37853169",
+ "id": "pmid:27864985",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/37853169",
- "title": "CANVAS-related RFC1 mutations in patients with immune-mediated neuropathy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27864985",
+ "title": "Telomeric repeat-containing RNA (TERRA) related to polycystic ovary syndrome (PCOS).",
"type": "article-journal",
- "doi": "10.1038/s41598-023-45011-8",
+ "doi": "10.1111/cen.13283",
"authors": [
- ["Makito", "Hirano"],
- ["Motoi", "Kuwahara"],
- ["Yuko", "Yamagishi"],
- ["Makoto", "Samukawa"],
- ["Kanako", "Fujii"],
- ["Shoko", "Yamashita"],
- ["Masahiro", "Ando"],
- ["Nobuyuki", "Oka"],
- ["Mamoru", "Nagano"],
- ["Taro", "Matsui"],
- ["Toshihide", "Takeuchi"],
- ["Kazumasa", "Saigoh"],
- ["Susumu", "Kusunoki"],
- ["Hiroshi", "Takashima"],
- ["Yoshitaka", "Nagai"]
+ ["Caiqin", "Wang"],
+ ["Fengxian", "Shen"],
+ ["Yuning", "Zhu"],
+ ["Yuying", "Fang"],
+ ["Shiming", "Lu"]
],
- "publisher": "Scientific reports",
- "issn": "2045-2322",
- "date": "2023-10-18",
- "abstract": "Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) has recently been attributed to biallelic repeat expansions in RFC1. More recently, the disease entity has expanded to atypical phenotypes, including chronic neuropathy without cerebellar ataxia or vestibular areflexia. Very recently, RFC1 expansions were found in patients with Sj\u00f6gren syndrome who had neuropathy that did not respond to immunotherapy. In this study RFC1 was examined in 240 patients with acute or chronic neuropathies, including 105 with Guillain-Barr\u00e9 syndrome or Miller Fisher syndrome, 76 with chronic inflammatory demyelinating polyneuropathy, and 59 with other types of chronic neuropathy. Biallelic RFC1 mutations were found in three patients with immune-mediated neuropathies, including Guillain-Barr\u00e9 syndrome, idiopathic sensory ataxic neuropathy, or anti-myelin-associated glycoprotein (MAG) neuropathy, who responded to immunotherapies. In addition, a patient with chronic sensory autonomic neuropathy had biallelic mutations, and subclinical changes in Schwann cells on nerve biopsy. In summary,\u00a0we found CANVAS-related RFC1 mutations in patients with treatable immune-mediated neuropathy or demyelinating neuropathy.",
+ "publisher": "Clinical endocrinology",
+ "issn": "1365-2265",
+ "date": "2016-12-19",
+ "abstract": "Telomeric repeat-containing RNA (TERRA) participates in the regulation of telomere length, and leucocyte telomere length (LTL) plays an important role in the pathophysiology of polycystic ovary syndrome (PCOS), but little is known about the role of TERRA in PCOS.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37853169"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27864985"
},
{
- "id": "pmid:37747091",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/37747091",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:37747091']' timed out after 3 seconds"
+ "id": "pmid:29767611",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/29767611",
+ "title": "Tandem repeats of TSER significantly influence the efficacy of 5-fluorouracil in the treatment of plantar warts.",
+ "type": "article-journal",
+ "doi": "10.2217/pme-2015-0014",
+ "authors": [
+ ["Yue", "Zhao"],
+ ["Wangqing", "Chen"],
+ ["Wu", "Zhu"],
+ ["Jie", "Li"],
+ ["Juan", "Su"],
+ ["Shuang", "Zhao"],
+ ["Mingliang", "Chen"],
+ ["Jianglin", "Zhang"],
+ ["Aiyuan", "Guo"],
+ ["Siyu", "Yan"],
+ ["Xingchen", "Zhou"],
+ ["Xinwei", "Kuang"],
+ ["Zhaoqian", "Liu"],
+ ["Dan", "Luo"],
+ ["Todd C", "Knepper"],
+ ["Yijing", "He"],
+ ["Xiang", "Chen"]
+ ],
+ "publisher": "Personalized medicine",
+ "issn": "1744-828X",
+ "date": "2016-04-26",
+ "abstract": "To identify potential genetic risk markers associated with 5-fluorouracil (5-FU) treatment outcomes in plantar warts patients.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29767611"
},
{
- "id": "pmid:37660923",
+ "id": "pmid:26189437",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/37660923",
- "title": "Pathogenic CANVAS-causing but not nonpathogenic RFC1 DNA/RNA repeat motifs form quadruplex or triplex structures.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26189437",
+ "title": "Increased risk of severe fluoropyrimidine-associated toxicity in patients carrying a G to C substitution in the first 28-bp tandem repeat of the thymidylate synthase 2R allele.",
"type": "article-journal",
- "doi": "10.1016/j.jbc.2023.105202",
+ "doi": "10.1002/ijc.29694",
"authors": [
- ["Mohammad Hossein", "Abdi"],
- ["Bita", "Zamiri"],
- ["Gholamreza", "Pazuki"],
- ["Soroush", "Sardari"],
- ["Christopher E", "Pearson"]
+ ["Didier", "Meulendijks"],
+ ["Bart A W", "Jacobs"],
+ ["Abidin", "Aliev"],
+ ["Dick", "Pluim"],
+ ["Erik", "van Werkhoven"],
+ ["Maarten J", "Deenen"],
+ ["Jos H", "Beijnen"],
+ ["Annemieke", "Cats"],
+ ["Jan H M", "Schellens"]
],
- "publisher": "The Journal of biological chemistry",
- "issn": "1083-351X",
- "date": "2023-09-01",
- "abstract": "Biallelic expansions of various tandem repeat sequence motifs are possible in RFC1 (replication factor C subunit 1), encoding the DNA replication/repair protein RFC1, yet only certain repeat motifs cause cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS). CANVAS presents enigmatic puzzles: The pathogenic path for CANVAS neither is known nor is it understood why some, but not all expanded, motifs are pathogenic. The most common pathogenic repeat is (AAGGG)n\u2022(CCCTT)n, whereas (AAAAG)n\u2022(CTTTT)n is the most common nonpathogenic motif. While both intronic motifs can be expanded and transcribed, only r(AAGGG)n is retained in the mutant RFC1 transcript. We show that only the pathogenic forms unusual nucleic acid structures. Specifically, DNA and RNA of the pathogenic d(AAGGG)4 and r(AAGGG)4 form G-quadruplexes in potassium solution. Nonpathogenic repeats did not form G-quadruplexes. Triple-stranded structures are formed by the pathogenic motifs but not by the nonpathogenic motifs. G- and C-richness of the pathogenic strands favor formation of G\u2022G\u2022G\u2022G-tetrads and protonated C+-G Hoogsteen base pairings, involved in quadruplex and triplex structures, respectively, stabilized by increased hydrogen bonds and pi-stacking interactions relative to A-T Hoogsteen pairs that could form by the nonpathogenic motif. The ligand, TMPyP4, binds the pathogenic quadruplexes. Formation of quadruplexes and triplexes by pathogenic repeats supports toxic-DNA and toxic-RNA modes of pathogenesis at the RFC1 gene and the RFC1 transcript. Our findings with short repeats provide insights into the disease specificity of pathogenic repeat motif sequences and reveal nucleic acid structural features that may be pathogenically involved and targeted therapeutically.",
+ "publisher": "International journal of cancer",
+ "issn": "1097-0215",
+ "date": "2015-10-01",
+ "abstract": "The fluoropyrimidines act by inhibiting thymidylate synthase (TS). Recent studies have shown that patients' risk of severe fluoropyrimidine-associated toxicity is affected by polymorphisms in the 5'-untranslated region of TYMS, the gene encoding TS. A G>C substitution in the promoter enhancer region of TYMS, rs183205964 (known as the 2RC allele), markedly reduces TS activity in vitro, but its clinical relevance is unknown. We determined rs183205964 in 1605 patients previously enrolled in a prospective multicenter study. Associations between putative low TS expression genotypes (3RC/2RC, 2RG/2RC, and 2RC/2RC) and severe toxicity were investigated using univariable and multivariable logistic regression. Activity of TS and TYMS gene expression were determined in peripheral blood mononuclear cells (PBMCs) of a patient carrying genotype 2RC/2RC and of a control group of healthy individuals. Among 1,605 patients, 28 patients (1.7%) carried the 2RC allele. Twenty patients (1.2%) carried a risk-associated genotype (2RG/2RC, n=13; 3RC/2RC, n=6; and 2RC/2RC, n=1), the eight remaining patients had genotype 3RG/2RC. Early severe toxicity and toxicity-related hospitalization were significantly more frequent in risk-associated genotype carriers (OR 3.0, 95%CI 1.04-8.93, p=0.043 and OR 3.8, 95%CI 1.19-11.9, p=0.024, respectively, in multivariable analysis). The patient with genotype 2RC/2RC was hospitalized twice and had severe febrile neutropenia, diarrhea, and hand-foot syndrome. Baseline TS activity and gene expression in PBMCs of this patient, and a healthy individual with the 2RC allele, were found to be within the normal range. Our study suggests that patients carrying rs183205964 are at strongly increased risk of severe, potentially life-threatening, toxicity when treated with fluoropyrimidines.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37660923"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26189437"
},
{
- "id": "pmid:37546920",
+ "id": "pmid:25536611",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/37546920",
- "title": "Pathogenic CANVAS (AAGGG)",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25536611",
+ "title": "The influence of methylenetetrahydrofolate reductase and thymidylate synthetase gene polymorphisms on lung adenocarcinoma occurrence.",
"type": "article-journal",
- "doi": "10.1101/2023.07.25.550509",
+ "doi": "",
"authors": [
- ["Julia A", "Hisey"],
- ["Elina A", "Radchenko"],
- ["Silvia", "Ceschi"],
- ["Anastasia", "Rastokina"],
- ["Nicholas H", "Mandel"],
- ["Ryan J", "McGinty"],
- ["Gabriel", "Matos-Rodrigues"],
- ["Alfredo", "Hernandez"],
- ["Andr\u00e9", "Nussenzweig"],
- ["Sergei M", "Mirkin"]
+ ["Milena", "Cavic"],
+ ["Ana", "Krivokuca"],
+ ["Jelena", "Spasic"],
+ ["Ksenija", "Brotto"],
+ ["Emina", "Malisic"],
+ ["Davorin", "Radosavljevic"],
+ ["Sinisa", "Radulovic"],
+ ["Radmila", "Jankovic"]
],
- "publisher": "bioRxiv : the preprint server for biology",
- "issn": "2692-8205",
- "date": "2023-07-26",
- "abstract": "CANVAS is a recently characterized repeat expansion disease, most commonly caused by homozygous expansions of an intronic (A",
+ "publisher": "Journal of B.U.ON. : official journal of the Balkan Union of Oncology",
+ "issn": "1107-0625",
+ "date": "2014-01-01",
+ "abstract": "Methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthetase (TYMS) are suggested as risk factors for lung cancer. The purpose of this study was to analyze the association of MTHFR C677T polymorphism and variable number tandem repeat 2R/3R and single nucleotide polymorphism G>C in the 3R allele of the TYMS gene with lung adenocarcinoma.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37546920"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25536611"
},
{
- "id": "pmid:37476326",
+ "id": "pmid:25366766",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/37476326",
- "title": "Lower Facial Dystonia: An Unexpected Presentation Associated with Pathogenic",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25366766",
+ "title": "Association between polymorphisms in the thymidylate synthase gene and risk of breast cancer in a Mexican population.",
"type": "article-journal",
- "doi": "10.1002/mdc3.13730",
+ "doi": "10.4238/2014.october.27.16",
"authors": [
- ["Joana", "Fonte"],
- ["C\u00e9lia", "Machado"],
- ["Jorge", "Oliveira"],
- ["Marina", "Magalh\u00e3es"]
+ ["A", "Quintero-Ramos"],
+ ["S A", "Guti\u00e9rrez-Rubio"],
+ ["A", "Del Toro-Arreola"],
+ ["R A", "Franco-Topete"],
+ ["A", "Oceguera-Villanueva"],
+ ["L M", "Jim\u00e9nez-P\u00e9rez"],
+ ["J M", "Castro-Cervantes"],
+ ["A", "Barrag\u00e1n-Ruiz"],
+ ["J G", "V\u00e1zquez-Camacho"],
+ ["A", "Daneri-Navarro"]
],
- "publisher": "Movement disorders clinical practice",
- "issn": "2330-1619",
- "date": "2023-04-06",
- "abstract": "",
+ "publisher": "Genetics and molecular research : GMR",
+ "issn": "1676-5680",
+ "date": "2014-10-27",
+ "abstract": "Breast cancer (BC) is the leading cause of cancer-related deaths among women in Mexico. Two single-nucleotide polymorphisms (SNPs) in the thymidylate synthase (TS) gene, the 28-base pair (bp) tandem repeat in the TS 5'-untranslated enhanced region (TSER) and the 6-bp insertion/deletion in the TS 3'-untranslated region (TS 3'-UTR), increase the rate of misincorporation of uridylate into DNA and may lead to chromosomal damage. We examined the association between these polymorphisms and BC risk in Mexican women according to menopause status. Mexican patients with initial BC diagnosis (N = 230) and 145 individuals from a reference general population group (RGP) were included. For statistical analysis, the BC group was divided into pre- and post-menopause groups (PRE and POST groups, respectively). We analyzed both TS polymorphisms (TSER and TS 3'-UTR) using polymerase chain reaction. Finetti analysis was used to evaluate inter-and intra-group differences. The results showed a high frequency for the 3R and ins6 alleles in the BC, RGP, PRE, and POST groups. No significant differences were observed for the TS and TSER genotype and allele frequency distributions between groups. We found that the TSER and TS 3'-UTR SNPs are not associated with BC risk in Mexican patients.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37476326"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25366766"
},
{
- "id": "pmid:37460231",
+ "id": "pmid:25294632",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/37460231",
- "title": "Frequency and Phenotype of",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25294632",
+ "title": "Phase II trial of carboplatin and pemetrexed as first-line chemotherapy for non-squamous non-small cell lung cancer, and correlation between the efficacy/toxicity and genetic polymorphisms associated with pemetrexed metabolism: Hokkaido Lung Cancer Clinical Study Group Trial (HOT) 0902.",
"type": "article-journal",
- "doi": "10.1212/wnl.0000000000207553",
+ "doi": "10.1007/s00280-014-2589-3",
"authors": [
- ["Andreas", "Trasch\u00fctz"],
- ["Felix", "Heindl"],
- ["Muhammad", "Bilal"],
- ["Annette M", "Hartmann"],
- ["Claudia", "Dufke"],
- ["Olaf", "Riess"],
- ["Andreas", "Zwergal"],
- ["Dan", "Rujescu"],
- ["Tobias", "Haack"],
- ["Matthis", "Synofzik"],
- ["Michael", "Strupp"]
+ ["Kenya", "Kanazawa"],
+ ["Hiroshi", "Yokouchi"],
+ ["Xintao", "Wang"],
+ ["Takashi", "Ishida"],
+ ["Yuka", "Fujita"],
+ ["Satoru", "Fujiuchi"],
+ ["Toshiyuki", "Harada"],
+ ["Masao", "Harada"],
+ ["Kei", "Takamura"],
+ ["Satoshi", "Oizumi"],
+ ["Ichiro", "Kinoshita"],
+ ["Yutaka", "Katsuura"],
+ ["Osamu", "Honjo"],
+ ["Tetsuya", "Kojima"],
+ ["Hirotoshi", "Dosaka-Akita"],
+ ["Hiroshi", "Isobe"],
+ ["Mitsuru", "Munakata"],
+ ["Masaharu", "Nishimura"]
],
- "publisher": "Neurology",
- "issn": "1526-632X",
- "date": "2023-07-17",
- "abstract": "Bilateral vestibulopathy (BVP) is a chronic debilitating neurologic disorder with no monogenic cause established so far despite familiar presentations. We hypothesized that replication factor complex subunit 1 (RFC1) repeat expansions might present a recurrent monogenic cause of BVP.",
+ "publisher": "Cancer chemotherapy and pharmacology",
+ "issn": "1432-0843",
+ "date": "2014-10-08",
+ "abstract": "This phase II study evaluated the response rate (RR) and safety of combination therapy with carboplatin (CBDCA) and pemetrexed (PEM) in Japanese patients with non-squamous non-small cell lung cancer (non-sq NSCLC). Further, the relationship between therapy efficacy/toxicity and genetic polymorphisms associated with PEM metabolism was analyzed.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37460231"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25294632"
},
{
- "id": "pmid:36805468",
+ "id": "pmid:25258183",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/36805468",
- "title": "Generation and heterozygous repair of human iPSC lines from three individuals with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) carrying biallelic AAGGG expansions in RFC1.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25258183",
+ "title": "Variable number tandem repeats in dopamine receptor D4 in Tourette's syndrome.",
"type": "article-journal",
- "doi": "10.1016/j.scr.2023.103047",
+ "doi": "10.1002/mds.26027",
"authors": [
- ["Kayli C", "Davies"],
- ["Kiymet", "Bozaoglu"],
- ["Paul J", "Lockhart"]
- ],
- "publisher": "Stem cell research",
- "issn": "1876-7753",
- "date": "2023-02-14",
- "abstract": "Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is a progressive neurodegenerative disorder predominantly caused by biallelic AAGGG expansions in the second intron of the RFC1 gene. Here, we used a simultaneous reprogramming and CRISPR-Cas9 genome editing approach to generate three patient iPSC lines with homozygous AAGGG expansions along with three heterozygous gene corrected iPSC lines. The iPSC lines expressed pluripotency markers, had a normal karyotype, and were able to differentiate into all three embryonic germ layers. These mutant and corrected iPSC lines will be a valuable tool for studying the molecular mechanisms underlying CANVAS.",
+ ["Shiguo", "Liu"],
+ ["Jiajia", "Cui"],
+ ["Xinhua", "Zhang"],
+ ["Weifeng", "Wu"],
+ ["Haitao", "Niu"],
+ ["Xu", "Ma"],
+ ["Hongmei", "Xu"],
+ ["Mingji", "Yi"]
+ ],
+ "publisher": "Movement disorders : official journal of the Movement Disorder Society",
+ "issn": "1531-8257",
+ "date": "2014-09-25",
+ "abstract": "We attempted to clarify the association between dopamine receptor D4 (DRD4) 48-bp variable number of tandem repeats (VNTR) polymorphism and Tourette's syndrome.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36805468"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25258183"
},
{
- "id": "pmid:36753892",
+ "id": "pmid:25028118",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/36753892",
- "title": "RFC1 repeat expansions and cerebellar ataxia, neuropathy and vestibular areflexia syndrome: Experience and perspectives from a neuromuscular disorders unit.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/25028118",
+ "title": "Polymorphisms in TS, MTHFR and ERCC1 genes as predictive markers in first-line platinum and pemetrexed therapy in NSCLC patients.",
"type": "article-journal",
- "doi": "10.1016/j.jns.2023.120565",
+ "doi": "10.1007/s00432-014-1756-6",
"authors": [
- ["Daniel", "S\u00e1nchez-Tejerina"],
- ["Paula Fernandez", "Alvarez"],
- ["Elena", "La\u00ednez"],
- ["Victoria Gonzalez", "Martinez"],
- ["Daniela Isabel", "Santa-Cruz"],
- ["Lena", "Verdaguer"],
- ["Margarida", "Gratac\u00f2s"],
- ["Jose Luis", "Seoane"],
- ["N\u00faria", "Raguer"],
- ["Jorge", "Hern\u00e1ndez-Vara"],
- ["Arnau", "Llaurad\u00f3"],
- ["Javier", "Sotoca"],
- ["Maria", "Salvado"],
- ["Elena Garcia", "Arumi"],
- ["Eduardo F", "Tizzano"],
- ["Ra\u00fal", "Juntas"]
+ ["Pawe\u0142", "Krawczyk"],
+ ["Tomasz", "Kucharczyk"],
+ ["Dariusz M", "Kowalski"],
+ ["Tomasz", "Powr\u00f3zek"],
+ ["Rodryg", "Ramlau"],
+ ["Ewa", "Kalinka-Warzocha"],
+ ["Kinga", "Winiarczyk"],
+ ["Magdalena", "Knetki-Wr\u00f3blewska"],
+ ["Kamila", "Wojas-Krawczyk"],
+ ["Katarzyna", "Ka\u0142akucka"],
+ ["Wojciech", "Dyszkiewicz"],
+ ["Maciej", "Krzakowski"],
+ ["Janusz", "Milanowski"]
],
- "publisher": "Journal of the neurological sciences",
- "issn": "1878-5883",
- "date": "2023-01-28",
- "abstract": "Pathogenic expansions in RFC1 have been described as a cause of a spectrum of disorders including late-onset ataxia, chronic cough, and cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). Sensory neuronopathy/neuropathy appears to be a major symptom of RFC1-disorder, and RFC1 expansions are common in patients with sensory chronic idiopathic axonal neuropathy or sensory ganglionopathy. We aimed to investigate RFC1 expansions in patients with suspected RFC1-related disease followed-up in a Neuromuscular Diseases Unit, with a particular interest in the involvement of the peripheral nervous system.",
+ "publisher": "Journal of cancer research and clinical oncology",
+ "issn": "1432-1335",
+ "date": "2014-07-16",
+ "abstract": "We presented retrospective analysis of up to five polymorphisms in TS, MTHFR and ERCC1 genes as molecular predictive markers for homogeneous Caucasian, non-squamous NSCLC patients treated with pemetrexed and platinum front-line chemotherapy.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36753892"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25028118"
},
{
- "id": "pmid:36705320",
+ "id": "pmid:24726028",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/36705320",
- "title": "Association of biallelic RFC1 expansion with early-onset Parkinson's disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/24726028",
+ "title": "Thymidylate synthase polymorphisms in genomic DNA as clinical outcome predictors in a European population of advanced non-small cell lung cancer patients receiving pemetrexed.",
"type": "article-journal",
- "doi": "10.1111/ene.15717",
+ "doi": "10.1186/1479-5876-12-98",
"authors": [
- ["Pauli", "Ylikotila"],
- ["Jussi", "Sipil\u00e4"],
- ["Tiina", "Alapirtti"],
- ["Riitta", "Ahmasalo"],
- ["Eriko", "Koshimizu"],
- ["Satoko", "Miyatake"],
- ["Anri", "Hurme-Niiranen"],
- ["Ari", "Siitonen"],
- ["Hiroshi", "Doi"],
- ["Fumiaki", "Tanaka"],
- ["Naomichi", "Matsumoto"],
- ["Kari", "Majamaa"],
- ["Laura", "Kyt\u00f6vuori"]
+ ["Estefan\u00eda", "Ar\u00e9valo"],
+ ["Eduardo", "Casta\u00f1\u00f3n"],
+ ["In\u00e9s", "L\u00f3pez"],
+ ["Josefa", "Salgado"],
+ ["V\u00edctor", "Collado"],
+ ["Marta", "Santisteban"],
+ ["Mar\u00eda", "Rodr\u00edguez-Ruiz"],
+ ["Patricia", "Mart\u00edn"],
+ ["Leire", "Zubiri"],
+ ["Ana", "Pati\u00f1o-Garc\u00eda"],
+ ["Christian", "Rolfo"],
+ ["Ignacio", "Gil-Bazo"]
],
- "publisher": "European journal of neurology",
- "issn": "1468-1331",
- "date": "2023-02-12",
- "abstract": "The biallelic repeat expansion (AAGGG)",
+ "publisher": "Journal of translational medicine",
+ "issn": "1479-5876",
+ "date": "2014-04-14",
+ "abstract": "We studied whether thymidylate synthase (TS) genotype has an independent prognostic/predictive impact on a European population of advanced non-small cell lung cancer (NSCLC) patients receiving pemetrexed.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36705320"
-},
-{
- "id": "pmid:36381255",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/36381255",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:36381255']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24726028"
},
{
- "id": "pmid:36289003",
+ "id": "pmid:24554028",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/36289003",
- "title": "Truncating Variants in",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/24554028",
+ "title": "Thymidylate synthase polymorphisms are associated to therapeutic outcome of advanced non-small cell lung cancer patients treated with platinum-based chemotherapy.",
"type": "article-journal",
- "doi": "10.1212/wnl.0000000000201486",
+ "doi": "10.1007/s11033-014-3197-3",
"authors": [
- ["Riccardo", "Ronco"],
- ["Cecilia", "Perini"],
- ["Riccardo", "Curr\u00f2"],
- ["Natalia", "Dominik"],
- ["Stefano", "Facchini"],
- ["Alice", "Gennari"],
- ["Roberto", "Simone"],
- ["Skye", "Stuart"],
- ["Sara", "Nagy"],
- ["Elisa", "Vegezzi"],
- ["Ilaria", "Quartesan"],
- ["Amar", "El-Saddig"],
- ["Timothy", "Lavin"],
- ["Arianna", "Tucci"],
- ["Agnieszka", "Szymura"],
- ["Luiz Eduardo", "Novis De Farias"],
- ["Alexander", "Gary"],
- ["Megan", "Delfeld"],
- ["Priscilla", "Kandikatla"],
- ["Nifang", "Niu"],
- ["Sanjukta", "Tawde"],
- ["Joseph", "Shaw"],
- ["James", "Polke"],
- ["Mary M", "Reilly"],
- ["Nick W", "Wood"],
- ["Emmanuele", "Crespan"],
- ["Christopher", "Gomez"],
- ["Jin Yun Helen", "Chen"],
- ["Jeremy Dan", "Schmahmann"],
- ["David", "Gosal"],
- ["Henry", "Houlden"],
- ["Soma", "Das"],
- ["Andrea", "Cortese"]
+ ["Aurea", "Lima"],
+ ["V\u00edtor", "Seabra"],
+ ["Sandra", "Martins"],
+ ["Ana", "Coelho"],
+ ["Ant\u00f3nio", "Ara\u00fajo"],
+ ["Rui", "Medeiros"]
],
- "publisher": "Neurology",
- "issn": "1526-632X",
- "date": "2022-10-26",
- "abstract": "Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is an autosomal recessive neurodegenerative disease characterized by adult-onset and slowly progressive sensory neuropathy, cerebellar dysfunction, and vestibular impairment. In most cases, the disease is caused by biallelic (AAGGG)",
+ "publisher": "Molecular biology reports",
+ "issn": "1573-4978",
+ "date": "2014-02-20",
+ "abstract": "Thymidylate synthase (TYMS) has three polymorphisms that may modulate thymidylate synthase (TS) expression levels: (1) 28 base pairs (bp) variable number tandem repeat (VNTR) (rs34743033); (2) single nucleotide polymorphism (SNP) C>G at the twelfth nucleotide of the second repeat of 3R allele (rs2853542); and (3) 6 bp sequence deletion (1494del6, rs34489327). This study was conducted to evaluate the influence of TYMS polymorphisms on the survival of Portuguese patients with advanced non-small cell lung cancer (NSCLC) undergoing platinum-based chemotherapy. Our results showed no statistically significant differences between VNTR genotypes; although, considering the SNP C>G, homozygotes 3RG presented a better prognostic at 36 months (p=0.004) and overall survival (p=0.003) when compared to 2R3RG patients. Patients with \"median/high expression genotypes\" demonstrated a better survival at 12 months (p=0.041) when compared to \"low expression genotypes\". Furthermore, 6 bp- carriers (p=0.006) showed a better survival at 12 months when compared to 6 bp+ homozygotes patients. When analyzing TYMS haplotypes, better survival at 12 months was observed for patients carrying haplotypes with the 6 bp- allele (2R6 bp-; p=0.026 and 3RG6 bp-; p=0.045). This is the first report that evaluates the three major TYMS polymorphisms in the therapeutic outcome of NSCLC in Portugal. According to our results, the TYMS polymorphisms may be useful tools to predict which advanced NSCLC patients could benefit more from platinum-based chemotherapy regimens.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36289003"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24554028"
},
{
- "id": "pmid:36250766",
+ "id": "pmid:24137384",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/36250766",
- "title": "New Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome cases are caused by the presence of a nonsense variant in compound heterozygosity with the pathogenic repeat expansion in the RFC1 gene.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/24137384",
+ "title": "Polymorphisms of",
"type": "article-journal",
- "doi": "10.1111/cge.14249",
+ "doi": "10.3892/ol.2013.1467",
"authors": [
- ["Ana", "Arteche-L\u00f3pez"],
- ["Almudena", "Avila-Fernandez"],
- ["Alejandra", "Damian"],
- ["Emma", "Soengas-Gonda"],
- ["Rub\u00e9n P\u00e9rez", "de la Fuente"],
- ["Patricia Ramos", "G\u00f3mez"],
- ["Jes\u00fas Gallego", "Merlo"],
- ["Laura Horcajada", "Burgos"],
- ["Carlos Cemill\u00e1n", "Fern\u00e1ndez"],
- ["Jose Miguel Lezana", "Rosales"],
- ["Juan Francisco Gonz\u00e1lez", "Mart\u00ednez"],
- ["Juan Francisco", "Quesada-Espinosa"],
- ["Marta", "Corton"],
- ["Maria Paz", "Guerrero-Molina"]
+ ["Kensuke", "Kumamoto"],
+ ["Keiichiro", "Ishibashi"],
+ ["Norimichi", "Okada"],
+ ["Yusuke", "Tajima"],
+ ["Kouki", "Kuwabara"],
+ ["Yoichi", "Kumagai"],
+ ["Hiroyuki", "Baba"],
+ ["Norihiro", "Haga"],
+ ["Hideyuki", "Ishida"]
],
- "publisher": "Clinical genetics",
- "issn": "1399-0004",
- "date": "2022-11-03",
- "abstract": "The biallelic pathogenic repeat (AAGGG)",
+ "publisher": "Oncology letters",
+ "issn": "1792-1074",
+ "date": "2013-07-15",
+ "abstract": "The aim of the current study was to examine whether polymorphisms in drug metabolism genes have any clinical impact on patients treated with 5-fluorouracil (FU)/oxaliplatin for metastatic colorectal cancer (MCRC). In total, 63 patients with MCRC were recruited and treated with a modified FOLFOX6 (mFOLFOX6) treatment as a first-line chemotherapy. Polymorphisms in five drug metabolism genes and two DNA-repair genes were assessed in these patients using polymerase chain reaction (PCR), a PCR restriction fragment length polymorphism (PCR-RFLP) technique or invader techniques. These included a 28-bp tandem repeat in the 5'-untranslated region (UTR) and 6-bp deletions in the 3'-UTR of thymidylate synthase (",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36250766"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24137384"
},
{
- "id": "pmid:36177974",
+ "id": "pmid:23968134",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/36177974",
- "title": "Severe distinct dysautonomia in RFC1-related disease associated with Parkinsonism.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23968134",
+ "title": "Thymidylate synthase gene polymorphism and survival of colorectal cancer patients receiving adjuvant 5-fluorouracil.",
"type": "article-journal",
- "doi": "10.1111/jns.12515",
+ "doi": "10.1089/gtmb.2013.0171",
"authors": [
- ["Christopher J", "Record"],
- ["Rana Alnasser", "Alsukhni"],
- ["Riccardo", "Curro"],
- ["Diego", "Kaski"],
- ["John S", "Rubin"],
- ["Huw R", "Morris"],
- ["Andrea", "Cortese"],
- ["Valeria", "Iodice"],
- ["Mary M", "Reilly"]
+ ["Violetta", "Sulzyc-Bielicka"],
+ ["Dariusz", "Bielicki"],
+ ["Agnieszka", "Binczak-Kuleta"],
+ ["Mariusz", "Kaczmarczyk"],
+ ["Wies\u0142awa", "Pioch"],
+ ["Anna", "Machoy-Mokrzynska"],
+ ["Andrzej", "Ciechanowicz"],
+ ["Magdalena", "Go\u0142\u0119biewska"],
+ ["Marek", "Drozdzik"]
],
- "publisher": "Journal of the peripheral nervous system : JPNS",
- "issn": "1529-8027",
- "date": "2022-10-07",
- "abstract": "Biallelic repeat expansions in replication factor C subunit 1 (RFC1) have recently been found to cause cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS). Additional features that have been described include Parkinsonism and a multiple system atrophy (MSA)-like syndrome. CANVAS can include features of dysautonomia, but they are much milder than typically seen in MSA. We report a detailed autonomic phenotype of multisystem RFC1-related disease presenting initially as CANVAS. Our patient presented aged 61 with a sensory ataxic neuropathy who rapidly developed widespread autonomic failure and Parkinsonism. The autonomic profile was of a mixed pre- and post-ganglionic syndrome with progressive involvement of sympathetic and parasympathetic cardiovascular and sudomotor function. The Parkinsonism did not respond to levodopa. We present a patient with CANVAS and biallelic RFC1 expansions who developed Parkinsonism with severe autonomic involvement similar to that seen in classical MSA. The link between MSA and CANVAS remains uncertain.",
+ "publisher": "Genetic testing and molecular biomarkers",
+ "issn": "1945-0257",
+ "date": "2013-08-22",
+ "abstract": "Limited studies indicate a possible association of 5'-UTR thymidylate synthase enhancer region polymorphism and treatment outcome in patients medicated with 5-fluorouracil (5-FU). The study was designed to verify the relationship in patients with colorectal cancer (CRC), a Polish population that received 5-FU-based adjuvant chemotherapy. The study analyzed 145 Astler-Coller B2 and C CRC patients. Genotyping for a variable number of tandem repeats and G to C single-nucleotide polymorphism in the 5'-UTR of the thymidylate synthase (TS) gene was carried out. TS genotypes were classified into high expression (high TS) and low expression types (low TS). High TS was found in 22.8% of patients. The right-side tumors were more frequently associated with high TS than the left-side tumors (p=0.024). High TS was only found in 9.3% of rectal tumors, but in 29.7% of colon cancers (p=0.0042). Disease-free survival after 20 months (DFS 20) was longer in subjects with low TS than in high TS (p=0.043). Patients who underwent chemotherapy had longer DFS 20 in the low TS than in the high TS subgroup (p=0.051). The low TS was found to be an independent good prognostic factor for DFS 20 in the whole group as well as in the subgroup treated with chemotherapy (p=0.024 and p=0.034, respectively). Patients with low TS did not show any differences in DFS 20 whether they were treated with adjuvant chemotherapy or not. Proximal CRC tumors are characterized by higher TS expression genotypes than distal tumors, and are at significantly greater risk of early recurrence during the first 20 months after surgery.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36177974"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23968134"
},
{
- "id": "pmid:36088850",
+ "id": "pmid:23481061",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/36088850",
- "title": "Cognitive impairment is not uncommon in patients with biallelic RFC1 AAGGG repeat expansion, but the expansion is rare in patients with cognitive disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23481061",
+ "title": "Genetic variability & chemotoxicity of 5-fluorouracil & cisplatin in head & neck cancer patients: a preliminary study.",
"type": "article-journal",
- "doi": "10.1016/j.parkreldis.2022.08.034",
- "authors": [
- ["Anita", "Korpioja"],
- ["Johanna", "Kr\u00fcger"],
- ["Anri", "Hurme-Niiranen"],
- ["Eino", "Solje"],
- ["Kasper", "Katisko"],
- ["Joonas", "Lipponen"],
- ["Maria", "Lehtilahti"],
- ["Anne M", "Remes"],
- ["Kari", "Majamaa"],
- ["Laura", "Kyt\u00f6vuori"]
+ "doi": "",
+ "authors": [
+ ["Dipali", "Dhawan"],
+ ["Harsha", "Panchal"],
+ ["Shilin", "Shukla"],
+ ["Harish", "Padh"]
],
- "publisher": "Parkinsonism & related disorders",
- "issn": "1873-5126",
- "date": "2022-09-06",
- "abstract": "The biallelic repeat expansion (AAGGG)",
+ "publisher": "The Indian journal of medical research",
+ "issn": "0975-9174",
+ "date": "2013-01-01",
+ "abstract": "background & objectives: The efficacy and toxicity of a given chemotherapy regimen varies widely among patients due to the inherited variability of genes that are involved in drug metabolism. There are several crucial enzymes identified involving metabolism of 5-fluorouracil (5-FU) and cisplatin, which are polymorphic. We studied head and neck cancer patients (n=23) on 5-FU and cisplatin combination therapy attending a tertiary care cancer research institute in Gujarat, India, to understand the effect of a particular genotype on toxicity.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36088850"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23481061"
},
{
- "id": "pmid:35633373",
+ "id": "pmid:23226765",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/35633373",
- "title": "Screening for RFC-1 pathological expansion in late-onset ataxias: a contribution to the differential diagnosis.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23226765",
+ "title": "Correlation between thymidylate synthase gene polymorphisms and efficacy of pemetrexed in advanced non-small cell lung cancer.",
"type": "article-journal",
- "doi": "10.1007/s00415-022-11192-x",
+ "doi": "10.3892/etm.2012.730",
"authors": [
- ["Melissa", "Barghigiani"],
- ["Giovanna", "De Michele"],
- ["Alessandra", "Tessa"],
- ["Tommasina", "Fico"],
- ["Gemma", "Natale"],
- ["Francesco", "Sacc\u00e0"],
- ["Chiara", "Pane"],
- ["Nunzia", "Cuomo"],
- ["Anna", "De Rosa"],
- ["Sabina", "Pappat\u00e0"],
- ["Giuseppe", "De Michele"],
- ["Filippo M", "Santorelli"],
- ["Alessandro", "Filla"]
+ ["Qiong", "Hu"],
+ ["Xuefei", "Li"],
+ ["Chunxia", "Su"],
+ ["Xiaoxia", "Chen"],
+ ["Guanghui", "Gao"],
+ ["Jie", "Zhang"],
+ ["Yinmin", "Zhao"],
+ ["Jiayu", "Li"],
+ ["Caicun", "Zhou"]
],
- "publisher": "Journal of neurology",
- "issn": "1432-1459",
- "date": "2022-05-28",
- "abstract": "We screened 62 late-onset ataxia patients for the AAGGG pathological expansion in the RFC-1 gene that, when biallelic, causes Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome (CANVAS). Nine patients tested positive. Six had a previous diagnosis of sporadic adult-onset ataxia (SAOA) and three of multisystem atrophy type C (MSA-C). Further six patients were heterozygous for the pathological RFC-1 expansion, four with an initial diagnosis of MSA-C and two of SAOA. In comparison with CANVAS, MSA-C patients had faster progression and shorter disease duration to walking with aids. An abnormal DaTscan does not seem to contribute to differential diagnosis between CANVAS and MSA-C.",
+ "publisher": "Experimental and therapeutic medicine",
+ "issn": "1792-0981",
+ "date": "2012-09-28",
+ "abstract": "One of the target genes of pemetrexed (PEM), thymidylate synthase (TS), has been shown to have a close association with its efficacy. TS gene polymorphisms have been shown to be associated with the efficacy of antifolate treatment in enteron tumors. The purpose of this study was to investigate the clinical significance of TS gene polymorphisms in patients with advanced NSCLC receiving PEM-based treatment. The variable nucleoid tandem repeat in the 5'-UTR region was amplified and detected using fluorescently labeled multiplex short tandem repeat polymerase chain reaction. The polymorphism in the 3'-UTR region of the TS gene was detected using the Taqman probe. Efficacy of PEM was assessed according to the Response Evaluation Criteria in Solid Tumors, version 1.1. None of the genotypes were associated with gender, smoking status and age. Disease control rate (DCR), objective response rate (ORR) and progression-free survival (PFS) were similar between patients harboring 2R and 3R alleles (PFS, p=0.518; DCR, p=0.631; ORR, p=0.541), as well as those with a 6-bp insertion and 6-bp deletion (PFS, p=0.776; DCR, p=0.626; ORR, p=0.330). To study the combined effect of TS polymorphisms, the study population was divided into three groups: 2R&6 del, 2R&6 ins and 3R&6 del. No significant differences were observed among the different groups according to DCR (p=0.517), ORR (p=0.611) and PFS (p=0.938). In conclusion, polymorphisms of the TS gene do not appear to be a prognostic marker for advanced NSCLC patients receiving PEM-based treatment.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35633373"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23226765"
},
{
- "id": "pmid:35585435",
+ "id": "pmid:22576918",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/35585435",
- "title": "Beyond canvas: behavioral onset of rfc1-expansion disease in an Italian family-causal or casual?",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22576918",
+ "title": "Thymidylate synthase enhancer region polymorphism not related to susceptibility to acute lymphoblastic leukemia in the Kashmir population.",
"type": "article-journal",
- "doi": "10.1007/s10072-022-06137-1",
+ "doi": "10.4238/2012.april.10.6",
"authors": [
- ["Fabiana", "Colucci"],
- ["Daniela", "Di Bella"],
- ["Chiara", "Pisciotta"],
- ["Elisa", "Sarto"],
- ["Francesca", "Gualandi"],
- ["Marcella", "Neri"],
- ["Alessandra", "Ferlini"],
- ["Elena", "Contaldi"],
- ["Maura", "Pugliatti"],
- ["Davide", "Pareyson"],
- ["Mariachiara", "Sensi"]
+ ["F H", "Nazki"],
+ ["A", "Masood"],
+ ["M A", "Banday"],
+ ["A", "Bhat"],
+ ["B A", "Ganai"]
],
- "publisher": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology",
- "issn": "1590-3478",
- "date": "2022-05-18",
- "abstract": "Biallelic intronic AAGGG repeat expansion in the replication factor C subunit 1 (RFC1) gene was recently identified in two/third of patients with cerebellar ataxia, sensory neuropathy, and bilateral vestibular areflexia syndrome (CANVAS). The phenotypic spectrum has expanded since (i.e., parkinsonism, motor neuron involvement, cognitive decline); no behavioral symptoms have been reported yet.",
+ "publisher": "Genetics and molecular research : GMR",
+ "issn": "1676-5680",
+ "date": "2012-04-10",
+ "abstract": "Thymidylate synthase (TS) is a crucial enzyme in folate metabolism and plays a vital role in DNA synthesis and repair. The most common polymorphism in TS is a unique double (2R) or triple (3R) 28-bp tandem repeat sequence in the enhancer region of the TS gene (TSER). This genetic variation in TSER has been widely investigated and has been implicated as a risk factor for the development of various cancers, including acute lymphoblastic leukemia. It has also been found to influence sensitivity to anti-cancer drugs, such as methotrexate. We evaluated this polymorphism in acute lymphoblastic leukemia patients in the Kashmir population. In order to determine whether a double (2R2R) versus a triple (3R3R) 28-bp tandem repeat in the TSER modulates risk for acute lymphoblastic leukemia, 72 acute lymphoblastic leukemia cases and 144 age and gender matched, unrelated healthy individuals from the Kashmir region of India were evaluated for this polymorphism by PCR and direct sequencing. We found the frequency of the TS 2R allele to be 32.6 and 26.0%, in cases and controls, respectively. The TS 2R/2R genotype was found to be present in 15.27% of the cases and 9.72% of the controls, the 2R/3R variant in 34.72% of the cases and 32.63% of the controls, and the 3R/3R genotype in 50.0% of the cases and 57.63% of the controls. There was a significant association between the TS 2R/2R genotype and gender of acute lymphoblastic leukemia patients with males harboring the 2R/2R genotype exhibiting a higher risk of developing acute lymphoblastic leukemia than females (P = 0.009) We concluded that the TSER polymorphism appears not to be a risk factor for susceptibility to acute lymphoblastic leukemia in the Kashmir population.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35585435"
-},
-{
- "id": "pmid:35013364",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/35013364",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:35013364']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22576918"
},
{
- "id": "pmid:34968871",
+ "id": "pmid:22044939",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/34968871",
- "title": "Cramp-fasciculation syndrome phenotype of cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) due to RFC1 repeat expansion.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22044939",
+ "title": "Impact of SHMT1 polymorphism on the clinical outcome of patients with metastatic colorectal cancer treated with first-line FOLFIRI+bevacizumab.",
"type": "article-journal",
- "doi": "10.1016/j.clinph.2021.11.005",
+ "doi": "10.1097/fpc.0b013e32834d8376",
"authors": [
- ["Hugo", "Kermorvant"],
- ["Rabab", "Debs"],
- ["Thierry", "Maisonobe"],
- ["Vincent", "Huin"],
- ["Tanya", "Stojkovic"],
- ["Timoth\u00e9e", "Lenglet"]
+ ["Barna", "Budai"],
+ ["Viktor", "Koml\u00f3si"],
+ ["Vilmos", "Adleff"],
+ ["\u00c9va", "Pap"],
+ ["Andrea", "R\u00e9ti"],
+ ["T\u00fcnde", "Nagy"],
+ ["Judit", "Kralov\u00e1nszky"],
+ ["Istv\u00e1n", "L\u00e1ng"],
+ ["Erika", "Hitre"]
],
- "publisher": "Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology",
- "issn": "1872-8952",
- "date": "2021-12-03",
- "abstract": "",
+ "publisher": "Pharmacogenetics and genomics",
+ "issn": "1744-6880",
+ "date": "2012-01-01",
+ "abstract": "The impact of thymidylate synthase (TYMS), methylenetetrahydrofolate reductase (MTHFR), and serine hydroxymethyltransferase 1 (SHMT1) gene polymorphisms and that of dihydropyrimidine dehydrogenase (DPD) enzyme activity, serum total homocysteine level, and estimated serum creatinine clearance on first-line 5-fluorouracil, leucovorin, irinotecan, and bevacizumab (FOLFIRI+bevacizumab) regimen efficacy in metastatic colorectal cancer patients was investigated. DNA was extracted from peripheral blood mononuclear cells. Genotyping was performed for TYMS 5'UTR variable number tandem repeat, TYMS 3'UTR ins/del, MTHFR C677T, and SHMT1 C1420T polymorphisms. The DPD activity of peripheral blood mononuclear cells was also determined. The univariate and multivariate analyses demonstrated that the SHMT1 1420T allele was associated with better response (P=0.025) and longer progression-free survival (PFS) (P=0.00004) and overall survival (OS) (P=0.034). Grade \u22652 hypertension was also an independent prognostic factor of longer progression-free survival and OS. Bevacizumab-related hypertension might be a predictive marker of treatment efficacy (P=0.0002 for OS) in the case of wild (CC) SHMT1 1420 genotypes only.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34968871"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22044939"
},
{
- "id": "pmid:33884451",
+ "id": "pmid:21196216",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/33884451",
- "title": "RFC1 AAGGG repeat expansion masquerading as Chronic Idiopathic Axonal Polyneuropathy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21196216",
+ "title": "TS gene tandem repeats in esophageal cancer patients receiving chemoradiotherapy.",
"type": "article-journal",
- "doi": "10.1007/s00415-021-10552-3",
+ "doi": "10.2741/3733",
"authors": [
- ["Matteo", "Tagliapietra"],
- ["Davide", "Cardellini"],
- ["Moreno", "Ferrarini"],
- ["Silvia", "Testi"],
- ["Sergio", "Ferrari"],
- ["Salvatore", "Monaco"],
- ["Tiziana", "Cavallaro"],
- ["Gian Maria", "Fabrizi"]
+ ["Kazuhiro", "Kaneko"],
+ ["Maho", "Nagai"],
+ ["Yoshitaka", "Murakami"],
+ ["Mari", "Kogo"],
+ ["Tsunehiro", "Oyama"],
+ ["Takashi", "Kojima"],
+ ["Atsushi", "Ohtsu"],
+ ["Michio", "Imawari"]
],
- "publisher": "Journal of neurology",
- "issn": "1432-1459",
- "date": "2021-04-21",
- "abstract": "A biallelic intronic AAGGG repeat expansion in the Replication Factor C subunit 1 (RFC1) gene has been recently associated with Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome, a disorder often presenting as a slowly evolving sensory neuropathy at the onset. \"Chronic Idiopathic Axonal Polyneuropathy\" (CIAP) is a common indolent axonal neuropathy of adulthood which remains without an identifiable cause despite thorough investigations.",
+ "publisher": "Frontiers in bioscience (Landmark edition)",
+ "issn": "2768-6698",
+ "date": "2011-01-01",
+ "abstract": "5-Fluorouracil (5-FU) interferes with tumor-cell proliferation by inhibiting thymidylate synthase (TS). We examined the relationship between tandem repeat (TR) variations in the TS gene and survival following concurrent chemoradiotherapy in patients with esophageal squamous cell carcinoma (ESCC). TS-TR variations were analyzed in 57 stage II-IV ESCC patients undergoing chemoradiotherapy combined with 5-FU and cisplatinum (CDDP), and in 106 controls. Pretreatment non-neoplastic biopsy specimens from ESCC patients and lymphocytes from controls were used for analysis. Variations were identified by the size of DNA fragments amplified by polymerase chain reaction. Two to five TRs were found in Japanese individuals. TR3 homozygotes were predominant in 74% of ESCC patients and 61% of controls. Three-year survival rates were significantly longer in patients with TR2/2 or TR2/3 genotypes (38%) than in patients with TR3/3, 3/4, or 3/5 genotypes (9%; p=0.011). In the Cox proportional hazard model, the TR2/2 or TR2/3 genotypes were the only independent predictor for survival (Hazard ratio, 2.647; 95% confidence interval, 1.271-5.513). The TS-TR variations exert an important influence on survival following chemoradiotherapy in ESCC patients.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33884451"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21196216"
},
{
- "id": "pmid:33807868",
+ "id": "pmid:20932673",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/33807868",
- "title": "Whole-Genome Sequencing in Diagnostics of Selected Slovenian Undiagnosed Patients with Rare Disorders.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/20932673",
+ "title": "Thymidylate synthase gene polymorphism affects the response to preoperative 5-fluorouracil chemoradiation therapy in patients with rectal cancer.",
"type": "article-journal",
- "doi": "10.3390/life11030205",
+ "doi": "10.1016/j.ijrobp.2010.06.049",
"authors": [
- ["Gaber", "Bergant"],
- ["Ale\u0161", "Maver"],
- ["Borut", "Peterlin"]
+ ["Hyuk", "Hur"],
+ ["Jeonghyun", "Kang"],
+ ["Nam Kyu", "Kim"],
+ ["Byung Soh", "Min"],
+ ["Kang Young", "Lee"],
+ ["Sang Joon", "Shin"],
+ ["Ki Chang", "Keum"],
+ ["Junjeong", "Choi"],
+ ["Hoguen", "Kim"],
+ ["Sung Ho", "Choi"],
+ ["Mi-Young", "Lee"]
],
- "publisher": "Life (Basel, Switzerland)",
- "issn": "2075-1729",
- "date": "2021-03-05",
- "abstract": "Several patients with rare genetic disorders remain undiagnosed following comprehensive diagnostic testing using whole-exome sequencing (WES). In these patients, pathogenic genetic variants may reside in intronic or regulatory regions or they may emerge through mutational mechanisms not detected by WES. For this reason, we implemented whole-genome sequencing (WGS) in routine clinical diagnostics of patients with undiagnosed genetic disorders and report on the outcome in 30 patients. Criteria for consideration included (1) negative WES, (2) a high likelihood of a genetic cause for the disorders, (3) positive family history, (4) detection of large blocks of homozygosity or (5) detection of a single pathogenic variant in a gene associated with recessive conditions. We successfully discovered a causative genetic variant in 6 cases, a retrotranspositional event in the APC gene, non-coding variants in the intronic region of the OTC gene and the promotor region of the UFM1 gene, repeat expansion in the RFC1 gene and a single exon duplication in the CNGB3 gene. We also discovered one coding variant, an indel, which was missed by variant caller during WES data analysis. Our study demonstrates the impact of WGS in the group of patients with undiagnosed genetic diseases after WES in the clinical setting and the diversity of mutational mechanisms discovered, which would remain undetected using other methods.",
+ "publisher": "International journal of radiation oncology, biology, physics",
+ "issn": "1879-355X",
+ "date": "2010-10-06",
+ "abstract": "This study aims to correlate thymidylate synthase (TS) gene polymorphisms with the tumor response to preoperative 5-fluorouracil (5-FU)-based chemoradiation therapy (CRT) in patients with rectal cancer.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33807868"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20932673"
},
{
- "id": "pmid:33068477",
+ "id": "pmid:20880668",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/33068477",
- "title": "Dopa-Responsive Parkinsonism in a Patient With Homozygous RFC1 Expansions.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/20880668",
+ "title": "Dyssynchronous systolic expansion of carotid artery in patients with marfan syndrome.",
"type": "article-journal",
- "doi": "10.1002/mds.28279",
+ "doi": "10.1016/j.echo.2010.08.022",
"authors": [
- ["Roisin", "Sullivan"],
- ["Wai Yan", "Yau"],
- ["Viorica", "Chelban"],
- ["Salvatore", "Rossi"],
- ["Emer", "O'Connor"],
- ["Nicholas W", "Wood"],
- ["Andrea", "Cortese"],
- ["Henry", "Houlden"]
+ ["Woo-In", "Yang"],
+ ["Chi-Young", "Shim"],
+ ["In-Jeong", "Cho"],
+ ["Hyuk-Jae", "Chang"],
+ ["Donghoon", "Choi"],
+ ["Yangsoo", "Jang"],
+ ["Namsik", "Chung"],
+ ["Seung-Yun", "Cho"],
+ ["Jong-Won", "Ha"]
],
- "publisher": "Movement disorders : official journal of the Movement Disorder Society",
- "issn": "1531-8257",
- "date": "2020-10-01",
- "abstract": "",
+ "publisher": "Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography",
+ "issn": "1097-6795",
+ "date": "2010-09-29",
+ "abstract": "Marfan syndrome is a multisystemic connective tissue disorder associated with a mutation affecting fibrillin-1, the main component of microfibrils. Fibrillin-1 gene mutations may affect the carotid arterial wall. The aim of this study was to investigate carotid arterial mechanics using Velocity Vector Imaging (VVI) in patients with Marfan syndrome.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33068477"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20880668"
},
{
- "id": "pmid:33068476",
+ "id": "pmid:20651387",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/33068476",
- "title": "Dopa-Responsive Parkinsonism in a Patient With Homozygous RFC1 Expansions.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/20651387",
+ "title": "Polymorphisms of thymidylate synthase gene 5'- and 3'-untranslated region and risk of gastric cancer in Koreans.",
"type": "article-journal",
- "doi": "10.1002/mds.28286",
+ "doi": "",
"authors": [
- ["Gabriel", "da Silva Schmitt"],
- ["Alberto R M", "Martinez"],
- ["Felipe F", "da Gra\u00e7a"],
- ["Fabr\u00edcio Diniz", "de Lima"],
- ["Luciana C", "Bonadia"],
- ["B\u00e1rbara Juarez", "Amorim"],
- ["Anamarli", "Nucci"],
- ["Marcondes Cavalcante", "Fran\u00e7a"]
+ ["Dong Jin", "Yim"],
+ ["Ok Jun", "Kim"],
+ ["Hee Jung", "An"],
+ ["Haeyoun", "Kang"],
+ ["Dae Ho", "Ahn"],
+ ["Seong Gyu", "Hwang"],
+ ["Doyeun", "Oh"],
+ ["Nam Keun", "Kim"]
],
- "publisher": "Movement disorders : official journal of the Movement Disorder Society",
- "issn": "1531-8257",
- "date": "2020-10-01",
- "abstract": "",
+ "publisher": "Anticancer research",
+ "issn": "1791-7530",
+ "date": "2010-06-01",
+ "abstract": "Thymidylate synthase (TS) plays an important role in the conversion of dUMP to dTMP. Polymorphisms of the TS gene affect the expression of the gene, which in turn may result in differences in the outcome of cancer chemotherapy and the progression of gastric cancer.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33068476"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20651387"
},
{
- "id": "pmid:32694621",
+ "id": "pmid:20372856",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/32694621",
- "title": "RFC1 repeat expansion in Japanese patients with late-onset cerebellar ataxia.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/20372856",
+ "title": "Influence of thymidylate synthase DNA polymorphisms and gender on the clinical evolution of patients with advanced colorectal cancer.",
"type": "article-journal",
- "doi": "10.1038/s10038-020-0807-x",
+ "doi": "10.3892/or_00000776",
"authors": [
- ["Mai", "Tsuchiya"],
- ["Haitian", "Nan"],
- ["Kishin", "Koh"],
- ["Yuta", "Ichinose"],
- ["Lihua", "Gao"],
- ["Keisuke", "Shimozono"],
- ["Takanori", "Hata"],
- ["Yeon-Jeong", "Kim"],
- ["Toshihisa", "Ohtsuka"],
- ["Andrea", "Cortese"],
- ["Yoshihisa", "Takiyama"]
+ ["Maria-Encarnaci\u00f3n", "Fern\u00e1ndez-Contreras"],
+ ["Jos\u00e9 Javier", "S\u00e1nchez-Hern\u00e1ndez"],
+ ["Mercedes", "Guijarro"],
+ ["Javier P", "Gisbert"],
+ ["Noa", "Rivas"],
+ ["Mar\u00eda-Luisa", "Garc\u00eda de Paredes"],
+ ["Adolfo", "Hinojar-Guti\u00e9rrez"],
+ ["Carlos", "Gamallo"]
],
- "publisher": "Journal of human genetics",
- "issn": "1435-232X",
- "date": "2020-07-21",
- "abstract": "Recently, the expansion of an intronic AAGGG repeat in the replication factor C subunit 1 (RFC1) gene was reported to cause cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). In Europeans, the expansion accounted for 22% of sporadic patients with late-onset ataxia. We genotyped 37 Japanese patients comprising 25 familial (autosomal recessive or undecided transmission) and 12 sporadic ones with late-onset ataxia. We found intronic repeat expansions in RFC1 in three (12%) of the familial patients and one (8.5%) of the sporadic ones. Although our cohort study was small, the disease frequency in Japanese patients with CANVAS might be lower than that in European ones. In addition, we found biallelic ACAGG repeat expansion in one patient, indicating ACAGG repeat expansion might cause CANVAS. Clinically, we found one patient with sleep apnea syndrome, which has not been reported previously. Thus, this study might expand the clinical and genetic spectrum of CANVAS.",
+ "publisher": "Oncology reports",
+ "issn": "1791-2431",
+ "date": "2010-05-01",
+ "abstract": "Experimental evidence has revealed that several thymidylate synthase (TS) DNA polymorphisms modulate gene expression, which, in turn is known to be down-regulated by oestrogen receptor subtypes. Consequently, this process might be influenced by female hormones. Based on these data, we investigated whether patient's gender and TS polymorphism exert an interactive effect on the clinical evolution of patients with advanced colorectal cancer (CRC) subjected to 5 fluorouracil (5FU)-based adjuvant chemotherapy. A retrospective study was carried out on paraffin-embedded sections from 81 CRC patients. A variable tandem repeat (VNTR) of 28 bp, a G/C single nucleotide polymorphism (SNP), and a deletion of 6 bp (ins1494del 6 bp) were studied. Genotyping methods were polymerase chain reaction (PCR) for VNTR, and PCR followed by restriction length fragment polymorphism (PCR-RFLP) for SNP and ins1494del 6 bp. The effect of TS genotype and gender on overall and progression-free survival was assessed in univariate and multivariate (Cox regression model) tests. In male patients, the study of combined TS genotypes showed that G&6+/6+ was an adverse marker for overall (P=0.04; median: not reached) and progression-free survival (P=0.03; median: 12 months, 95% CI: 0-32.4). In the multivariate analysis, the concurrence of G&6+/6+ combination and male patients resulted in a 5.5-fold increased risk of relapse or disease progression (95% CI: 1-32.1; likelihood test P=0.004; interaction P=0.06). TS genotype did not affect survival among women. The present study supports that the effect of TS polymorphisms on the clinical evolution of advanced CRC patients is significantly influenced by gender.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32694621"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20372856"
},
{
- "id": "pmid:32682126",
+ "id": "pmid:20005374",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/32682126",
- "title": "False-positive anti-neuronal nuclear antibody type 1 in a patient with RFC1 repeat expansion: Preventing \"phenotype creep\" in autoimmune neurology.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/20005374",
+ "title": "A significant expansion of CD8+ CD28- T-suppressor cells in adult-to-adult living donor liver transplant recipients.",
"type": "article-journal",
- "doi": "10.1016/j.jns.2020.117018",
+ "doi": "10.1016/j.transproceed.2009.09.072",
"authors": [
- ["Adrian", "Budhram"],
- ["John R", "Mills"],
- ["Kamal", "Shouman"],
- ["P James B", "Dyck"],
- ["Anhar", "Hassan"],
- ["Nicholas L", "Zalewski"]
+ ["Y-X", "Lin"],
+ ["L-N", "Yan"],
+ ["B", "Li"],
+ ["L-L", "Wang"],
+ ["T-F", "Wen"],
+ ["Y", "Zeng"],
+ ["W-T", "Wang"],
+ ["J-C", "Zhao"],
+ ["J-Y", "Yang"],
+ ["M-Q", "Xu"],
+ ["Y-K", "Ma"],
+ ["Z-Y", "Chen"],
+ ["Y-J", "Bai"]
],
- "publisher": "Journal of the neurological sciences",
- "issn": "1878-5883",
- "date": "2020-07-09",
- "abstract": "",
+ "publisher": "Transplantation proceedings",
+ "issn": "1873-2623",
+ "date": "2009-12-01",
+ "abstract": "The appearance of human regulatory CD8(+) CD28(-) T-suppressor (Ts) cells has been associated with a reduced need for maintenance immunosuppression in cadaveric heart- kidney transplant recipients and pediatric liver-intestine transplant recipients. However, few data are available in adult-to-adult living donor liver transplantation (A-A LDLT).",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32682126"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20005374"
},
{
- "id": "pmid:31370354",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/31370354",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:31370354']' timed out after 3 seconds"
+ "id": "pmid:19306093",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19306093",
+ "title": "Thymidylate synthetase allelic imbalance in clear cell renal carcinoma.",
+ "type": "article-journal",
+ "doi": "10.1007/s00280-009-0986-9",
+ "authors": [
+ ["Davide", "Colavito"],
+ ["Giuseppe", "Cartei"],
+ ["Massimo", "Dal Bianco"],
+ ["Anna", "Stecca"],
+ ["Fable", "Zustovich"],
+ ["Maurizio", "Dalle Carbonare"],
+ ["Eugenio", "Ragazzi"],
+ ["Miriam", "Farina"],
+ ["Eva", "Colombrino"],
+ ["Alberta", "Leon"]
+ ],
+ "publisher": "Cancer chemotherapy and pharmacology",
+ "issn": "1432-0843",
+ "date": "2009-03-22",
+ "abstract": "To investigate the allelic status of the thymidylate synthetase (TYMS) gene, located at chromosome band 18p11.32, in renal cell carcinoma (RCC). TYMS is a key target of the 5-fluorouracil (5-FU)-based class of drugs, frequently considered in combination therapies in advanced RCC. TYMS variants, such as the TYMS polymorphic 5'-untranslated region variable number tandem repeat sequence (VNTR), are under investigation to guide 5-FU treatment. Yet, no information is available with regard to changes in TYMS allele frequencies in RCC malignances.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19306093"
},
{
- "id": "pmid:30926972",
+ "id": "pmid:18273818",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/30926972",
- "title": "Biallelic expansion of an intronic repeat in RFC1 is a common cause of late-onset ataxia.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18273818",
+ "title": "Size of the exon 1-CAG repeats of the androgen receptor gene employed as a molecular marker in the diagnosis of Turner syndrome in girls with short stature.",
"type": "article-journal",
- "doi": "10.1038/s41588-019-0372-4",
+ "doi": "10.4238/vol7-1gmr391",
"authors": [
- ["Andrea", "Cortese"],
- ["Roberto", "Simone"],
- ["Roisin", "Sullivan"],
- ["Jana", "Vandrovcova"],
- ["Huma", "Tariq"],
- ["Wai Yan", "Yau"],
- ["Jack", "Humphrey"],
- ["Zane", "Jaunmuktane"],
- ["Prasanth", "Sivakumar"],
- ["James", "Polke"],
- ["Muhammad", "Ilyas"],
- ["Eloise", "Tribollet"],
- ["Pedro J", "Tomaselli"],
- ["Grazia", "Devigili"],
- ["Ilaria", "Callegari"],
- ["Maurizio", "Versino"],
- ["Vincenzo", "Salpietro"],
- ["Stephanie", "Efthymiou"],
- ["Diego", "Kaski"],
- ["Nick W", "Wood"],
- ["Nadja S", "Andrade"],
- ["Elena", "Buglo"],
- ["Adriana", "Rebelo"],
- ["Alexander M", "Rossor"],
- ["Adolfo", "Bronstein"],
- ["Pietro", "Fratta"],
- ["Wilson J", "Marques"],
- ["Stephan", "Z\u00fcchner"],
- ["Mary M", "Reilly"],
- ["Henry", "Houlden"]
+ ["C C", "Figueiredo"],
+ ["C", "Kochi"],
+ ["C A", "Longui"],
+ ["M N", "Rocha"],
+ ["F", "Richeti"],
+ ["N M A", "Evangelista"],
+ ["L E P", "Calliari"],
+ ["O", "Monte"]
],
- "publisher": "Nature genetics",
- "issn": "1546-1718",
- "date": "2019-03-29",
- "abstract": "Late-onset ataxia is common, often idiopathic, and can result from cerebellar, proprioceptive, or vestibular impairment; when in combination, it is also termed cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). We used non-parametric linkage analysis and genome sequencing to identify a biallelic intronic AAGGG repeat expansion in the replication factor C subunit 1 (RFC1) gene as the cause of familial CANVAS and a frequent cause of late-onset ataxia, particularly if sensory neuronopathy and bilateral vestibular areflexia coexist. The expansion, which occurs in the poly(A) tail of an AluSx3 element and differs in both size and nucleotide sequence from the reference (AAAAG)",
+ "publisher": "Genetics and molecular research : GMR",
+ "issn": "1676-5680",
+ "date": "2008-01-22",
+ "abstract": "Turner syndrome (TS) is one of the most common chromosomal abnormalities among girls. Complete monosomy of X chromosome is responsible for almost 50% of all cases of TS, and mosaicism and X anomaly are detected in the other half. It has already been demonstrated that early diagnosis of these children allows appropriate growth hormone treatment with better final height prognosis and introduction of estrogen at an ideal chronological age. Sixty-four short-stature girls were selected and the clinical data obtained were birth weight and height, weight and height at the first medical visit and target height. Other clinical data including cardiac and renal abnormalities, otitis, Hashimoto thyroiditis, cubitus valgus, short neck, widely separated nipples, and pigmented nevi were obtained from the patients' medical records. The aim of the present study was to evaluate the screening of a group of short-stature girls for TS based on the number of CAG repeats of the androgen receptor gene analyzed by GeneScan software. Patient samples with two alleles (heterozygous) were 49/64 (76.5%) and with one allele (homozygous) were 15/64 (23.5%). A karyotype was determined in 30 patients, 9 homozygous and 21 heterozygous. In the homozygous group, 6/9 were 45,X and 3/9 were 46,XX. In the heterozygous group, 17/21 were 46,XX, and 4/21 were TS patients with mosaicism (45,X/46,XX; 45,X/46XiXq; 46XdelXp). The pattern obtained by GeneScan in two patients with mosaicism in the karyotype was an imbalance between the peak heights of the two alleles, suggesting that this imbalance could be present when there is a mosaicism. The frequency of TS abnormalities (18.7%) did not differ between TS and 46,XX girls. Thus, it is important to accurately assess the incidence of TS in growth-retarded girls, even in the absence of other dysmorphisms. In this study, we diagnosed 6 cases of TS 45,X (9.4%) by molecular analysis, with a 100% sensitivity and 85% specificity. This molecular analysis was able to detect all cases of TS 45,X and the majority of mosaicisms, without the need for more X chromosome markers. In conclusion, determining the number of CAG repeats of the androgen receptor gene analyzed by GeneScan was a fast method with high sensitivity for the detection of TS 45,X, suggesting that it could be interesting as a method for screening a population of growth-retarded girls.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30926972"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18273818"
},
{
- "id": "pmid:12556494",
+ "id": "pmid:18267032",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/12556494",
- "title": "Replication and expansion of trinucleotide repeats in yeast.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18267032",
+ "title": "ERCC2 2251A>C genetic polymorphism was highly correlated with early relapse in high-risk stage II and stage III colorectal cancer patients: a preliminary study.",
"type": "article-journal",
- "doi": "10.1128/mcb.23.4.1349-1357.2003",
+ "doi": "10.1186/1471-2407-8-50",
"authors": [
- ["Richard", "Pelletier"],
- ["Maria M", "Krasilnikova"],
- ["George M", "Samadashwily"],
- ["Robert", "Lahue"],
- ["Sergei M", "Mirkin"]
+ ["Ming-Yii", "Huang"],
+ ["Wei-Yu", "Fang"],
+ ["Su-Chen", "Lee"],
+ ["Tian-Lu", "Cheng"],
+ ["Jaw-Yuan", "Wang"],
+ ["Shiu-Ru", "Lin"]
],
- "publisher": "Molecular and cellular biology",
- "issn": "0270-7306",
- "date": "2003-02-01",
- "abstract": "The mechanisms of trinucleotide repeat expansions, underlying more than a dozen hereditary neurological disorders, are yet to be understood. Here we looked at the replication of (CGG)(n) x (CCG)(n) and (CAG)(n) x (CTG)(n) repeats and their propensity to expand in Saccharomyces cerevisiae. Using electrophoretic analysis of replication intermediates, we found that (CGG)(n) x (CCG)(n) repeats significantly attenuate replication fork progression. Replication inhibition for this sequence becomes evident at as few as approximately 10 repeats and reaches a maximal level at 30 to 40 repeats. This is the first direct demonstration of replication attenuation by a triplet repeat in a eukaryotic system in vivo. For (CAG)(n) x (CTG)(n) repeats, on the contrary, there is only a marginal replication inhibition even at 80 repeats. The propensity of trinucleotide repeats to expand was evaluated in a parallel genetic study. In wild-type cells, expansions of (CGG)(25) x (CCG)(25) and (CAG)(25) x (CTG)(25) repeat tracts occurred with similar low rates. A mutation in the large subunit of the replicative replication factor C complex (rfc1-1) increased the expansion rate for the (CGG)(25) repeat approximately 50-fold but had a much smaller effect on the expansion of the (CTG)(25) repeat. These data show dramatic sequence-specific expansion effects due to a mutation in the lagging strand DNA synthesis machinery. Together, the results of this study suggest that expansions are likely to result when the replication fork attempts to escape from the stall site.",
+ "publisher": "BMC cancer",
+ "issn": "1471-2407",
+ "date": "2008-02-12",
+ "abstract": "Early relapse in colorectal cancer (CRC) patients is attributed mainly to the higher malignant entity (such as an unfavorable genotype, deeper tumor invasion, lymph node metastasis and advance cancer stage) and poor response to chemotherapy. Several investigations have demonstrated that genetic polymorphisms in drug-targeted genes, metabolizing enzymes, and DNA-repairing enzymes are all strongly correlated with inter-individual differences in the efficacy and toxicity of many treatment regimens. This preliminary study attempts to identify the correlation between genetic polymorphisms and clinicopathological features of CRC, and evaluates the relationship between genetic polymorphisms and chemotherapeutic susceptibility of Taiwanese CRC patients. To our knowledge, this study discusses, for the first time, early cancer relapse and its indication by multiple genes.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12556494"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18267032"
},
{
- "id": "pmid:39044557",
+ "id": "pmid:17278107",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/39044557",
- "title": "Clinical and pathological characteristics of OPDM4 patients in advanced disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17278107",
+ "title": "Identification of a novel single nucleotide polymorphism in the first tandem repeat sequence of the thymidylate synthase 2R allele.",
"type": "article-journal",
- "doi": "10.1002/mus.28200",
+ "doi": "10.1002/ijc.22568",
"authors": [
- ["Haixia", "Tang"],
- ["Ying", "Xiong"],
- ["Kaiyan", "Jiang"],
- ["Yu", "Shen"],
- ["Yanyan", "Yu"],
- ["Pengcheng", "Huang"],
- ["Min", "Zhu"],
- ["Xiaobing", "Li"],
- ["Yilei", "Zheng"],
- ["Meihong", "Zhou"],
- ["Jiaxi", "Yu"],
- ["Jianwen", "Deng"],
- ["Zhaoxia", "Wang"],
- ["Daojun", "Hong"],
- ["Yusen", "Qiu"],
- ["Dandan", "Tan"]
+ ["Lisa F", "Lincz"],
+ ["Fiona E", "Scorgie"],
+ ["Madhu B", "Garg"],
+ ["Stephen P", "Ackland"]
],
- "publisher": "Muscle & nerve",
- "issn": "1097-4598",
- "date": "2024-07-23",
- "abstract": "Oculopharyngodistal myopathy type 4 (OPDM4) arises from a CGG repeat expansion in the 5' UTR of the RILPL1 gene. Reported cases of OPDM4 have been limited. The aim of this study was to investigate the clinical and myopathological characteristics of OPDM4 patients with advanced disease.",
+ "publisher": "International journal of cancer",
+ "issn": "0020-7136",
+ "date": "2007-05-01",
+ "abstract": "Thymidylate synthase (TS) activity is an important determinant of response to chemotherapy with fluoropyrimidine prodrugs and its expression is largely determined by the number of functional upstream stimulatory factor (USF) E-box consensus elements present in the 5'regulatory region of the TYMS gene. Two known polymorphisms in this area, a variable number of tandem repeat (VNTR) consisting of 2 or 3 repeats (2R/3R) of a 28-bp sequence and a further G > C single nucleotide substitution within the second repeat of the 3R, result in genotypes with between 2 and 4 functional repeats in most humans. Here, we identify a further G > C SNP in the first repeat of the TYMS 2R allele, which effectively abolishes the only functional USF protein binding site in this promoter. The frequency of the new allele was found to be 4.2% (95% CI = 1.4-9.6%), accounting for 8.8% (95% CI = 2.9-19.3%) of all 2R alleles in our patient cohort. Thus, we observed that the lowest number of inherited functional binding sites is 1 instead of 2 as previously thought, and could potentially be 0 in a homozygous individual. This would severely decrease TS expression and may have implications for predicting efficacy and toxicity of therapy with commonly used fluorouracil-based therapy regimes.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39044557"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17278107"
},
{
- "id": "pmid:19264154",
+ "id": "pmid:17273745",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/19264154",
- "title": "The polycystic kidney disease 1 (Pkd1) gene is required for the responses of osteochondroprogenitor cells to midpalatal suture expansion in mice.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17273745",
+ "title": "Combined analysis of genetic polymorphisms in thymidylate synthase, uridine diphosphate glucoronosyltransferase and X-ray cross complementing factor 1 genes as a prognostic factor in advanced colorectal cancer patients treated with 5-fluorouracil plus oxaliplatin or irinotecan.",
"type": "article-journal",
- "doi": "10.1016/j.bone.2009.02.018",
+ "doi": "",
"authors": [
- ["Bo", "Hou"],
- ["Elona", "Kolpakova-Hart"],
- ["Naomi", "Fukai"],
- ["Kimberly", "Wu"],
- ["Bjorn R", "Olsen"]
+ ["Eva", "Martinez-Balibrea"],
+ ["Jose Luis", "Manzano"],
+ ["Anna", "Martinez-Cardus"],
+ ["Teresa", "Moran"],
+ ["Beatriz", "Cirauqui"],
+ ["Silvia", "Catot"],
+ ["Miguel", "Taron"],
+ ["Albert", "Abad"]
],
- "publisher": "Bone",
- "issn": "1873-2763",
- "date": "2009-03-02",
- "abstract": "Mechanical stress is known to modulate postnatal skeletal growth and development. However, the mechanisms underlying the mechanotransduction are not fully understood. Polycystin-1 (PC1) is a promising candidate among proteins that may play a role in the process as it has been shown to function as a flow sensor in renal epithelium and it is known to be important for skeletal development. To investigate whether PC1 is involved in mechanotransduction in skeletal tissues, mice with a conditional deficiency for PC1 in neural crest cells, osteoblasts or chondrocytes were subjected to midpalatal suture expansion. Dynamic bone labeling revealed that new bone formation in response to expansion was significantly reduced in Wnt1Cre;Pkd1 mice, as the suture area containing new bone was 14.0+/-3.4% in mutant mice versus 65.0+/-3.8% in control mice at 2 weeks (p<0.001). In contrast, stress-induced new bone formation was not affected in OsxCre;Pkd1 mice. The increase in cell proliferation and differentiation into osteoblasts, seen in wild-type mice 1 day after force delivery, was not observed until 14 days in Wnt1Cre;Pkd1 mice. TUNEL labeling showed a significant increase in apoptotic suture cells at days 1 and 3 (from 7.0+/-0.5% to 13.5+/-1.4% at day 1 and from 4.6+/-1.1% to 10.5+/-1.7% at day 3, p<0.05). Abnormal ossification of nasal cartilage of Wnt1Cre;Pkd1 mice was accelerated upon suture expansion. Such ossification was also observed, but to a lesser extent in Col2a1-ERCre;Pkd1 mice. Transcript levels of Runx2 and MMP13 were significantly increased in the nasal cartilage of Wnt1Cre;Pkd1 mice compared to controls (p<0.05 and p<0.001, respectively), and in mutant mice with expansion versus without expansion (p<0.05 and p<0.001, respectively). Lack of PC1 in chondroprogenitor cells also resulted in increased cell apoptosis and an altered arrangement of chondrocytes in nasal cartilage. These results indicate that PC1 plays a critical role in the response of osteochondroprogenitor cells to the mechanical tissue stress induced by midpalatal suture expansion. They also suggest that the combination of an in vivo mechanical model, such as midpalatal suture expansion, with conditional deficiency for proteins that play a role in mechanotransduction, represents a powerful experimental strategy to explore underlying mechanisms.",
+ "publisher": "Oncology reports",
+ "issn": "1021-335X",
+ "date": "2007-03-01",
+ "abstract": "The aim of this study was to investigate the influence of combining thymidylate synthase (TS), X-ray cross complementing factor 1 (XRCC1) and uridine diphosphate glucoronosyltransferase (UGT1A1 *28) polymorphism genotypes in response rate and time to progression (TTP) in metastatic colorectal cancer patients treated with 5-fluorouracil (5-FU) plus irinotecan or oxaliplatin (OXA). PCR, RFLP, allelic discrimination and direct sequencing were performed to elucidate TS, XRCC1 and UGT1A1 *28 genotypes in blood from 71 patients. Patients with a number of favourable genotypes (NFG) > or =1 had a lower progression rate and a better TTP than patients with NFG=0 (log-rank p<0.03). In the OXA + 5-FU group, patients with the TS 5' single nucleotide polymorphism and/or XRCC1 genotypes favourable to treatment had a better TTP (log-rank p=0.02). The TS 5' tandem repeat polymorphism and the NFG were independent prognostic factors in the Cox-based multivariate analysis (p<0.03). These results confirm the influence on patient out-come of these genetic polymorphisms and the possibility of studying them together to predict the outcome in first-line treated colorectal cancer patients.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19264154"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17273745"
},
{
- "id": "pmid:38467733",
+ "id": "pmid:16929515",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/38467733",
- "title": "Origin and evolution of pentanucleotide repeat expansions at the familial cortical myoclonic tremor with epilepsy type1 - SAMD12 locus.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/16929515",
+ "title": "The thymidylate synthase tandem repeat promoter polymorphism: A predictor for tumor-related survival in neoadjuvant treated locally advanced gastric cancer.",
"type": "article-journal",
- "doi": "10.1038/s41431-024-01586-y",
+ "doi": "10.1002/ijc.22235",
"authors": [
- ["Xinhui", "Chen"],
- ["Fan", "Zhang"],
- ["Yihua", "Shi"],
- ["Haotian", "Wang"],
- ["Miao", "Chen"],
- ["Dehao", "Yang"],
- ["Lebo", "Wang"],
- ["Peng", "Liu"],
- ["Fei", "Xie"],
- ["Jiawen", "Chen"],
- ["Aisi", "Fu"],
- ["Ben", "Hu"],
- ["Bo", "Wang"],
- ["Zhiyuan", "Ouyang"],
- ["Sheng", "Wu"],
- ["Zhiru", "Lin"],
- ["Zhidong", "Cen"],
- ["Wei", "Luo"]
+ ["Katja", "Ott"],
+ ["Holger", "Vogelsang"],
+ ["Noemi", "Marton"],
+ ["Karen", "Becker"],
+ ["Florian", "Lordick"],
+ ["Michael", "Kobl"],
+ ["Christoph", "Schuhmacher"],
+ ["Alexander", "Novotny"],
+ ["James", "Mueller"],
+ ["Ulrich", "Fink"],
+ ["Kurt", "Ulm"],
+ ["J\u00f6rg R\u00fcdiger", "Siewert"],
+ ["Heinz", "H\u00f6fler"],
+ ["Gisela", "Keller"]
],
- "publisher": "European journal of human genetics : EJHG",
- "issn": "1476-5438",
- "date": "2024-03-12",
- "abstract": "Familial cortical myoclonic tremor with epilepsy type 1 (FCMTE1) is caused by (TTTTA)exp(TTTCA)exp repeat expansions in SAMD12, while pure (TTTTA)exp is polymorphic. Our investigation focused on the origin and evolution of pure (TTTTA)exp and (TTTTA)exp(TTTCA)exp at this locus. We observed a founder effect between them. The phylogenetic analysis suggested that the (TTTTA)exp(TTTCA)exp might be generated from pure (TTTTA)exp through infrequent transformation events. Long-read sequencing revealed somatic generation of (TTTTA)exp(TTTCA)exp from pure (TTTTA)exp, likely via long segment (TTTCA) repeats insertion. Our findings indicate close relationships between the non-pathogenic (TTTTA)exp and the pathogenic (TTTTA)exp(TTTCA)exp, with dynamic interconversions. This sheds light on the genesis of pathogenic repeat expansions from ancestral premutation alleles. Our results may guide future studies in detecting novel repeat expansion disorders and elucidating repeat expansion mutational processes, thereby enhancing our understanding of human genomic variation.",
+ "publisher": "International journal of cancer",
+ "issn": "0020-7136",
+ "date": "2006-12-15",
+ "abstract": "We evaluated DNA polymorphisms in the thymidylate synthase (TS) and 5,10-methylene-tetrahydrofolate reductase (MTHFR) genes for an association with response and survival in locally advanced gastric cancer treated with 5-FU based preoperative chemotherapy (CTx). DNA of 238 patients (CTx-group: total n = 135, completely resected (R0) n = 102; without CTx: R0 n = 103) was isolated from blood or from nontumorous tissues. In the CTx-group, genotyping of the tandem repeat and the G/C polymorphism in the triple repeat in the promoter region of the TS gene and of the C677T polymorphism of the MTHFR gene was performed. None of the TS or MTHFR genotypes were associated with histopathological response and only the TS tandem repeat polymorphism was significantly related to survival (all patients n = 135, p = 0.002; R0 resected patients n = 102, p = 0.007; log-rank test). Multivariate analysis revealed ypN (p < 0.001) and the TS tandem repeat polymorphism as independent prognostic factors in the CTx-R0-group (p = 0.003). Analyzing the prognostic significance of the TS polymorphisms in the R0-group without CTx, TS genotypes were not significantly associated with survival. Comparing survival between R0 patients with and without CTx in the respective TS genotype groups of the tandem repeat polymorphism, a significant survival benefit for the patients with CTx was found for the 2rpt/2rpt (n = 49; p = 0.002) and 2rpt/3rpt genotypes (n = 99; p = 0.004), but not for the 3rpt/3rpt genotype (n = 57; p = 0.93). Patients' survival after CTx was associated with the TS tandem repeat polymorphism. CTx did not improve survival of patients with the 3rpt/3rpt genotype. Thus, a different therapy might be more appropriate for these patients.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38467733"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16929515"
},
{
- "id": "pmid:33681653",
+ "id": "pmid:16818689",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/33681653",
- "title": "Clinical and genomic analysis of a large Chinese family with familial cortical myoclonic tremor with epilepsy and",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/16818689",
+ "title": "Orotate phosphoribosyltransferase gene polymorphism predicts toxicity in patients treated with bolus 5-fluorouracil regimen.",
"type": "article-journal",
- "doi": "10.1002/epi4.12450",
+ "doi": "10.1158/1078-0432.ccr-05-2665",
"authors": [
- ["Yongxing", "Zhou"],
- ["Raman", "Sood"],
- ["Qun", "Wang"],
- ["Blake", "Carrington"],
- ["Morgan", "Park"],
- ["Alice C", "Young"],
- ["Daniel", "Birnbaum"],
- ["Zhao", "Liu"],
- ["Tetsuo", "Ashizawa"],
- ["James C", "Mullikin"],
- ["Mohamad Z", "Koubeissi"],
- ["Paul", "Liu"]
+ ["Wataru", "Ichikawa"],
+ ["Takehiro", "Takahashi"],
+ ["Kenichi", "Suto"],
+ ["Yasutsuna", "Sasaki"],
+ ["Renzo", "Hirayama"]
],
- "publisher": "Epilepsia open",
- "issn": "2470-9239",
- "date": "2021-02-02",
- "abstract": "Our goal was to perform detailed clinical and genomic analysis of a large multigenerational Chinese family with 21 individuals showing symptoms of Familial Cortical Myoclonic Tremor with Epilepsy (FCMTE) that we have followed for over 20\u00a0years.",
+ "publisher": "Clinical cancer research : an official journal of the American Association for Cancer Research",
+ "issn": "1078-0432",
+ "date": "2006-07-01",
+ "abstract": "We investigated whether the determination of orotate phosphoribosyltransferase (OPRT) and thymidylate synthase (TYMS) polymorphisms could predict the toxicity of 5-fluorouracil (5-FU) in colorectal cancer patients.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33681653"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16818689"
},
{
- "id": "pmid:33501421",
+ "id": "pmid:16182121",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/33501421",
- "title": "Genomic analysis of patients in a South Indian Community with autosomal dominant cortical tremor, myoclonus and epilepsy suggests a founder repeat expansion mutation in the",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/16182121",
+ "title": "Relationships between promoter polymorphisms in the thymidylate synthase gene and mRNA levels in colorectal cancers.",
"type": "article-journal",
- "doi": "10.1093/braincomms/fcaa214",
+ "doi": "10.1016/j.ejca.2005.06.016",
"authors": [
- ["Radha", "Mahadevan"],
- ["Rahul C", "Bhoyar"],
- ["Natarajan", "Viswanathan"],
- ["Raskin Erusan", "Rajagopal"],
- ["Bobby", "Essaki"],
- ["Varun", "Suroliya"],
- ["Rachel", "Chelladurai"],
- ["Saravanan", "Sankaralingam"],
- ["Ganesan", "Shanmugam"],
- ["Sriramakrishnan", "Vayanakkan"],
- ["Uzma", "Shamim"],
- ["Aradhana", "Mathur"],
- ["Abhinav", "Jain"],
- ["Mohamed", "Imran"],
- ["Mohammed", "Faruq"],
- ["Vinod", "Scaria"],
- ["Sridhar", "Sivasubbu"],
- ["Shantaraman", "Kalyanaraman"]
+ ["Maria", "Morganti"],
+ ["Monica", "Ciantelli"],
+ ["Beatrice", "Giglioni"],
+ ["Anna L", "Putignano"],
+ ["Stefania", "Nobili"],
+ ["Laura", "Papi"],
+ ["Ida", "Landini"],
+ ["Cristina", "Napoli"],
+ ["Rosa", "Valanzano"],
+ ["Fabio", "Cianchi"],
+ ["Vieri", "Boddi"],
+ ["Francesco", "Tonelli"],
+ ["Camillo", "Cortesini"],
+ ["Teresita", "Mazzei"],
+ ["Maurizio", "Genuardi"],
+ ["Enrico", "Mini"]
],
- "publisher": "Brain communications",
- "issn": "2632-1297",
- "date": "2020-12-19",
- "abstract": "Autosomal Dominant Cortical Tremor, Myoclonus and Epilepsy is a non-progressive disorder characterized by distal tremors. Autosomal Dominant Cortical Tremor, Myoclonus and Epilepsy has been reported globally with different genetic predispositions of autosomal dominant inheritance with a high degree of penetrance. In south India, Autosomal Dominant Cortical Tremor, Myoclonus and Epilepsy has been reported in a large cohort of 48 families, in which the genetic defect was not identified. This report pertains to the whole-genome analysis of four individuals followed by repeat-primed PCR for 102 patients from a familial cohort of 325 individuals. All the patients underwent extensive clinical evaluation including neuropsychological examinations. The whole-genome sequencing was done for two affected and two unaffected individuals, belonging to two different families. The whole-genome sequencing analysis revealed the repeat expansion of TTTTA and TTTCA in intron 4 of the",
+ "publisher": "European journal of cancer (Oxford, England : 1990)",
+ "issn": "0959-8049",
+ "date": "2005-09-01",
+ "abstract": "Thymidylate synthase (TS) intratumoural expression may be a prognostic marker and predict outcome of 5-fluorouracil (5-FU)-based chemotherapy in colorectal cancer patients. The TS gene promoter enhancer region contains two different polymorphisms which can influence TS mRNA transcriptional and translational efficiency: a polymorphic tandem repeat sequence (2 or 3 repeats; 2R and 3R) and a single nucleotide polymorphism (SNP), G > C, within the second repeat of the 3R alleles. We studied the relationship between tumoural TS mRNA expression levels and TS gene polymorphisms in the colonic mucosa of 48 colorectal cancer patients. The 3R/3R genotype was characterised by higher TS mRNA levels in the tumour than the 2R/2R-2R/3R genotypes (P = 0.071). Regarding the relationship with the SNP polymorphism, a statistically significant difference in TS gene expression between the 3RG/3RG genotype and 2R/2R-2R/3RC-2R/3RG genotype subset was observed (P = 0.017). No statistically significant correlation was observed between experimental data and baseline clinical-pathological characteristics as well as clinical outcome in the relatively small patient series investigated. This is the first study reporting an association between the TS intra-repeat SNP and gene expression levels in colorectal cancer patients. These results suggest that in 3R/3R patients, the G > C polymorphism may be an important factor in determining TS mRNA expression levels, and warrant further investigation of the role of TS promoter polymorphisms as predictors of sensitivity to 5-FU-based chemotherapy in larger case series.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33501421"
-},
-{
- "id": "pmid:32174879",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/32174879",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:32174879']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16182121"
},
{
- "id": "pmid:30559482",
+ "id": "pmid:15510613",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/30559482",
- "title": "Detecting a long insertion variant in SAMD12 by SMRT sequencing: implications of long-read whole-genome sequencing for repeat expansion diseases.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15510613",
+ "title": "Methylenetetrahydrofolate reductase and thymidylate synthase polymorphisms are not associated with breast cancer risk or phenotype.",
"type": "article-journal",
- "doi": "10.1038/s10038-018-0551-7",
+ "doi": "",
"authors": [
- ["Takeshi", "Mizuguchi"],
- ["Tomoko", "Toyota"],
- ["Hiroaki", "Adachi"],
- ["Noriko", "Miyake"],
- ["Naomichi", "Matsumoto"],
- ["Satoko", "Miyatake"]
+ ["Fabienne", "Grieu"],
+ ["Brenda", "Powell"],
+ ["John", "Beilby"],
+ ["Barry", "Iacopetta"]
],
- "publisher": "Journal of human genetics",
- "issn": "1435-232X",
- "date": "2018-12-17",
- "abstract": "Long-read sequencing technology is now capable of reading single-molecule DNA with an average read length of more than 10\u2009kb, fully enabling the coverage of large structural variations (SVs). This advantage may pave the way for the detection of unprecedented SVs as well as repeat expansions. Pathogenic SVs of only known genes used to be selectively analyzed based on prior knowledge of target DNA sequence. The unbiased application of long-read whole-genome sequencing (WGS) for the detection of pathogenic SVs has just begun. Here, we apply PacBio SMRT sequencing in a Japanese family with benign adult familial myoclonus epilepsy (BAFME). Our SV selection of low-coverage WGS data (7\u00d7) narrowed down the candidates to only six SVs in a 7.16-Mb region of the BAFME1 locus and correctly determined an approximately 4.6-kb SAMD12 intronic repeat insertion, which is causal of BAFME1. These results indicate that long-read WGS is potentially useful for evaluating all of the known SVs in a genome and identifying new disease-causing SVs in combination with other genetic methods to resolve the genetic causes of currently unexplained diseases.",
+ "publisher": "Anticancer research",
+ "issn": "0250-7005",
+ "date": "2004-01-01",
+ "abstract": "Aberrations in folate metabolism contribute to the risk of cancer via effects on the synthesis, methylation and repair of DNA. Functional genetic variants in the methylene tetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) genes may be risk factors for breast cancer because of their central roles in cellular folate metabolism.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30559482"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15510613"
},
{
- "id": "pmid:40463055",
+ "id": "pmid:15115918",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/40463055",
- "title": "",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15115918",
+ "title": "A 6 bp polymorphism in the thymidylate synthase gene causes message instability and is associated with decreased intratumoral TS mRNA levels.",
"type": "article-journal",
- "doi": "10.1101/2025.05.14.653432",
+ "doi": "10.1097/00008571-200405000-00007",
"authors": [
- ["Alan Mejia", "Maza"],
- ["Madison", "Hincher"],
- ["Kevin", "Correia"],
- ["Tammy", "Gillis"],
- ["Ayumi", "Nishiyama"],
- ["Ellen B", "Penney"],
- ["Aloysius", "Domingo"],
- ["Rachita", "Yadav"],
- ["Micaela G", "Murcar"],
- ["Patrick D Villafria", "Mercado"],
- ["Justin S", "Han"],
- ["Ean P", "Norenberg"],
- ["Cara", "Fernandez-Cerado"],
- ["G Paul", "Legarda"],
- ["Michelle", "Sy"],
- ["Edwin", "Mu\u00f1oz"],
- ["Mark C", "Ang"],
- ["Cid Czarina E", "Diesta"],
- ["Criscely", "Go"],
- ["Nutan", "Sharma"],
- ["D Cristopher", "Bragg"],
- ["Michael E", "Talkowski"],
- ["Marcy E", "MacDonald"],
- ["Jong-Min", "Lee"],
- ["Laurie J", "Ozelius"],
- ["Vanessa Chantal", "Wheeler"]
+ ["Michael V", "Mandola"],
+ ["Jan", "Stoehlmacher"],
+ ["Wu", "Zhang"],
+ ["Susan", "Groshen"],
+ ["Mimi C", "Yu"],
+ ["Syma", "Iqbal"],
+ ["Heinz-Josef", "Lenz"],
+ ["Robert D", "Ladner"]
],
- "publisher": "bioRxiv : the preprint server for biology",
- "issn": "2692-8205",
- "date": "2025-05-16",
- "abstract": "X-linked dystonia parkinsonism (XDP) is a progressive adult-onset neurogenerative disorder caused by the insertion of a SINE-VNTR-Alu (SVA) retrotransposon in",
+ "publisher": "Pharmacogenetics",
+ "issn": "0960-314X",
+ "date": "2004-05-01",
+ "abstract": "A 6 bp deletion polymorphism in the thymidylate synthase (TS) gene was investigated in order to determine its function.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40463055"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15115918"
},
{
- "id": "pmid:38834915",
+ "id": "pmid:12460463",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/38834915",
- "title": "Mini-heterochromatin domains constrain the cis-regulatory impact of SVA transposons in human brain development and disease.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/12460463",
+ "title": "Functional polymorphism of the thymidylate synthase gene in colorectal cancer accompanied by frequent loss of heterozygosity.",
"type": "article-journal",
- "doi": "10.1038/s41594-024-01320-8",
+ "doi": "10.1111/j.1349-7006.2002.tb01227.x",
"authors": [
- ["Vivien", "Horv\u00e1th"],
- ["Raquel", "Garza"],
- ["Marie E", "J\u00f6nsson"],
- ["Pia A", "Johansson"],
- ["Anita", "Adami"],
- ["Georgia", "Christoforidou"],
- ["Ofelia", "Karlsson"],
- ["Laura", "Castilla Vallmanya"],
- ["Symela", "Koutounidou"],
- ["Patricia", "Gerdes"],
- ["Ninoslav", "Pandiloski"],
- ["Christopher H", "Douse"],
- ["Johan", "Jakobsson"]
- ],
- "publisher": "Nature structural & molecular biology",
- "issn": "1545-9985",
- "date": "2024-06-04",
- "abstract": "SVA (SINE (short interspersed nuclear element)-VNTR (variable number of tandem repeats)-Alu) retrotransposons remain active in humans and contribute to individual genetic variation. Polymorphic SVA alleles harbor gene regulatory potential and can cause genetic disease. However, how SVA insertions are controlled and functionally impact human disease is unknown. Here we dissect the epigenetic regulation and influence of SVAs in cellular models of X-linked dystonia parkinsonism (XDP), a neurodegenerative disorder caused by an SVA insertion at the TAF1 locus. We demonstrate that the KRAB zinc finger protein ZNF91 establishes H3K9me3 and DNA methylation over SVAs, including polymorphic alleles, in human neural progenitor cells. The resulting mini-heterochromatin domains attenuate the cis-regulatory impact of SVAs. This is critical for XDP pathology; removal of local heterochromatin severely aggravates the XDP molecular phenotype, resulting in increased TAF1 intron retention and reduced expression. Our results provide unique mechanistic insights into how human polymorphic transposon insertions are recognized and how their regulatory impact is constrained by an innate epigenetic defense system.",
+ ["Kazuyuki", "Kawakami"],
+ ["Yoshinori", "Ishida"],
+ ["Kathleen D", "Danenberg"],
+ ["Kenji", "Omura"],
+ ["Go", "Watanabe"],
+ ["Peter V", "Danenberg"]
+ ],
+ "publisher": "Japanese journal of cancer research : Gann",
+ "issn": "0910-5050",
+ "date": "2002-11-01",
+ "abstract": "The thymidylate synthase (TS) gene has a polymorphic repeated sequence in its 5'-untranslated region. The repeat length is associated with TS protein expression, which suggests that we may be able to predict the efficacy of 5-fluorouracil (5-FU)-based chemotherapy from a patient's TS genotype determined through analysis of normal tissue obtained non-invasively. However, it is not yet elucidated whether the TS genotype is identical in tumor and normal tissue. In this study, we investigated the TS genotype in 151 matched tumor and normal DNA samples isolated from colorectal cancer and adjacent normal tissues by PCR analysis. The results showed that TS genotypes are identical in normal and tumor tissues of homozygous individuals, suggesting that the repeat sequence is stable through carcinogenesis. However, in heterozygous samples, an imbalance between the 2R and 3R alleles in the tumor DNA was frequently observed, suggesting loss of heterozygosity (LOH) at the TS locus. Detailed LOH analysis revealed that 62% (31 of 50) of 2R/3R-heterozygous samples had LOH. Frequent LOH at the TS locus was confirmed by RT-PCR of TS mRNA and microsatellite analysis using the marker D18S59, located on 18p11.3. There was no difference in the expressions of TS mRNA and TS protein between LOH and non-LOH samples. However, when the heterozygous genotype bearing LOH was subdivided according to the number of repeats, the cancer tissue with 2R/loss genotype expressed a significantly lower level of TS protein than did that with 3R/loss genotype. The results suggest that the difference in TS genotype between tumor and normal tissue due to LOH should be considered when the genotype is analyzed with normal tissue, such as peripheral blood cells, because it is important for TS protein expression.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38834915"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12460463"
},
{
- "id": "pmid:38616406",
+ "id": "pmid:11913730",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/38616406",
- "title": "Stability of Mosaic Divergent Repeat Interruptions in X-Linked Dystonia-Parkinsonism.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11913730",
+ "title": "Thymidylate synthase gene polymorphism determines response and toxicity of 5-FU chemotherapy.",
"type": "article-journal",
- "doi": "10.1002/mds.29809",
+ "doi": "10.1038/sj.tpj.6500012",
"authors": [
- ["Joshua", "La\u00df"],
- ["Theresa", "L\u00fcth"],
- ["Kathleen", "Schl\u00fcter"],
- ["Susen", "Schaake"],
- ["Bj\u00f6rn-Hergen", "Laabs"],
- ["Christoph", "Much"],
- ["Roland Dominic", "Jamora"],
- ["Raymond L", "Rosales"],
- ["Gerard", "Saranza"],
- ["Cid Czarina E", "Diesta"],
- ["Christopher E", "Pearson"],
- ["Inke R", "K\u00f6nig"],
- ["Norbert", "Br\u00fcggemann"],
- ["Christine", "Klein"],
- ["Ana", "Westenberger"],
- ["Joanne", "Trinh"]
+ ["S T", "Pullarkat"],
+ ["J", "Stoehlmacher"],
+ ["V", "Ghaderi"],
+ ["Y P", "Xiong"],
+ ["S A", "Ingles"],
+ ["A", "Sherrod"],
+ ["R", "Warren"],
+ ["D", "Tsao-Wei"],
+ ["S", "Groshen"],
+ ["H J", "Lenz"]
],
- "publisher": "Movement disorders : official journal of the Movement Disorder Society",
- "issn": "1531-8257",
- "date": "2024-04-14",
- "abstract": "X-Linked dystonia-parkinsonism (XDP) is an adult-onset neurodegenerative disorder characterized by rapidly progressive dystonia and parkinsonism. Mosaic Divergent Repeat Interruptions affecting motif Length and Sequence (mDRILS) were recently found within the TAF1 SVA repeat tract and were shown to associate with repeat stability and age at onset in XDP, specifically the AGGG [5'-SINE-VNTR-Alu(AGAGGG)",
+ "publisher": "The pharmacogenomics journal",
+ "issn": "1470-269X",
+ "date": "2001-01-01",
+ "abstract": "Thymidylate synthase (TS) catalyses the conversion of deoxy-uridylate to deoxy-thymidylate and is essential for DNA synthesis. The human TS gene promoter is polymorphic, having either double or triple tandem repeats of a 28-bp sequence. Here we determined the significance of this polymorphism in humans and its prediction for clinical outcome of patients with metastatic colorectal cancer treated with 5-fluorouracil. The TS mRNA level was analyzed using RT-PCR. Individuals homozygous for the triple repeat variant (L/L) had 3.6 times higher TS mRNA levels compared to those homozygous for the double repeat variant (S/S) in tumor tissue (P = 0.004). We tested 50 patients with disseminated colorectal cancer who received 5-FU treatment to determine whether this TS polymorphism will predict clinical outcome. We found individuals with S/S genotype had a response rate of 50% (4/8) when compared to 9% (2/22) in those with L/L and 15% (3/20) in those with S/L genotype (P = 0.041). Patients with L/L had less severe side effects to 5-FU (P = 0.008). The data suggest that genotyping for the TS polymorphism may have the potential to identify patients more likely to respond to 5-FU based chemotherapy.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38616406"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11913730"
},
{
- "id": "pmid:38835911",
+ "id": "pmid:10652619",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/38835911",
- "title": "Factors influencing reduced penetrance and variable expressivity in X-linked dystonia-parkinsonism.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/10652619",
+ "title": "Polymorphic tandem repeats in the thymidylate synthase gene is associated with its protein expression in human gastrointestinal cancers.",
"type": "article-journal",
- "doi": "10.1515/medgen-2022-2135",
+ "doi": "",
"authors": [
- ["Jelena", "Pozojevic"],
- ["Bj\u00f6rn-Hergen", "von Holt"],
- ["Ana", "Westenberger"]
+ ["K", "Kawakami"],
+ ["K", "Omura"],
+ ["E", "Kanehira"],
+ ["Y", "Watanabe"]
],
- "publisher": "Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V",
- "issn": "1863-5490",
- "date": "2022-08-12",
- "abstract": "X-linked dystonia-parkinsonism (XDP) is a neurodegenerative movement disorder that primarily affects adult Filipino men. It is caused by a founder retrotransposon insertion in",
+ "publisher": "Anticancer research",
+ "issn": "0250-7005",
+ "date": "1999-01-01",
+ "abstract": "Thymidylate synthase (TS) is a target enzyme of 5-fluorouracil (5-FU), and the TS gene has a polymorphic tandem repeated sequence in the 5'-untranslated region. We investigated the polymorphism on the repeat length of the TS gene and its relation to the number of 5-fluoro-dUMP (FdUMP) binding sites in human gastrointestinal cancers.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38835911"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10652619"
},
{
- "id": "pmid:38835428",
+ "id": "pmid:38684900",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/38835428",
- "title": "X-linked dystonia-parkinsonism: over and above a repeat disorder.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38684900",
+ "title": "A GGC-repeat expansion in ZFHX3 encoding polyglycine causes spinocerebellar ataxia type 4 and impairs autophagy.",
"type": "article-journal",
- "doi": "10.1515/medgen-2021-2105",
+ "doi": "10.1038/s41588-024-01719-5",
"authors": [
+ ["Karla P", "Figueroa"],
+ ["Caspar", "Gross"],
+ ["Elena", "Buena-Atienza"],
+ ["Sharan", "Paul"],
+ ["Mandi", "Gandelman"],
+ ["Naseebullah", "Kakar"],
+ ["Marc", "Sturm"],
+ ["Nicolas", "Casadei"],
+ ["Jakob", "Admard"],
+ ["Joohyun", "Park"],
+ ["Christine", "Z\u00fchlke"],
+ ["Yorck", "Hellenbroich"],
["Jelena", "Pozojevic"],
- ["Joseph Neos", "Cruz"],
- ["Ana", "Westenberger"]
+ ["Saranya", "Balachandran"],
+ ["Kristian", "H\u00e4ndler"],
+ ["Simone", "Zittel"],
+ ["Dagmar", "Timmann"],
+ ["Friedrich", "Erdlenbruch"],
+ ["Laura", "Herrmann"],
+ ["Thomas", "Feindt"],
+ ["Martin", "Zenker"],
+ ["Thomas", "Klopstock"],
+ ["Claudia", "Dufke"],
+ ["Daniel R", "Scoles"],
+ ["Arnulf", "Koeppen"],
+ ["Malte", "Spielmann"],
+ ["Olaf", "Riess"],
+ ["Stephan", "Ossowski"],
+ ["Tobias B", "Haack"],
+ ["Stefan M", "Pulst"]
],
- "publisher": "Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V",
- "issn": "1863-5490",
- "date": "2022-01-12",
- "abstract": "X-linked dystonia-parkinsonism (XDP) is an adult-onset neurodegenerative movement disorder, caused by a founder retrotransposon insertion in an intron of the",
+ "publisher": "Nature genetics",
+ "issn": "1546-1718",
+ "date": "2024-04-29",
+ "abstract": "Despite linkage to chromosome 16q in 1996, the mutation causing spinocerebellar ataxia type 4 (SCA4), a late-onset sensory and cerebellar ataxia, remained unknown. Here, using long-read single-strand whole-genome sequencing (LR-GS), we identified a heterozygous GGC-repeat expansion in a large Utah pedigree encoding polyglycine (polyG) in zinc finger homeobox protein 3 (ZFHX3), also known as AT-binding transcription factor 1 (ATBF1). We queried 6,495 genome sequencing datasets and identified the repeat expansion in seven additional pedigrees. Ultrarare DNA variants near the repeat expansion indicate a common distant founder event in Sweden. Intranuclear ZFHX3-p62-ubiquitin aggregates were abundant in SCA4 basis pontis neurons. In fibroblasts and induced pluripotent stem cells, the GGC expansion led to increased ZFHX3 protein levels and abnormal autophagy, which were normalized with small interfering RNA-mediated ZFHX3 knockdown in both cell types. Improving autophagy points to a therapeutic avenue for this novel polyG disease. The coding GGC-repeat expansion in an extremely G+C-rich region was not detectable by short-read whole-exome sequencing, which demonstrates the power of LR-GS for variant discovery.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38835428"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38684900"
},
{
- "id": "pmid:34250228",
+ "id": "doi:10.17161/2tmg0f25",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/34250228",
- "title": "Brain Regional Differences in Hexanucleotide Repeat Length in X-Linked Dystonia-Parkinsonism Using Nanopore Sequencing.",
+ "title": "A Case of Very Late Onset Spinobulbar Muscular Atrophy with Normal Creatine Kinase",
"type": "article-journal",
- "doi": "10.1212/nxg.0000000000000608",
+ "doi": "10.17161/2tmg0f25",
"authors": [
- ["Charles Jourdan", "Reyes"],
- ["Bj\u00f6rn-Hergen", "Laabs"],
- ["Susen", "Schaake"],
- ["Theresa", "L\u00fcth"],
- ["Raphaela", "Ardicoglu"],
- ["Aleksandar", "Rakovic"],
- ["Karen", "Gr\u00fctz"],
- ["Daniel", "Alvarez-Fischer"],
- ["Roland Dominic", "Jamora"],
- ["Raymond L", "Rosales"],
- ["Imke", "Weyers"],
- ["Inke R", "K\u00f6nig"],
- ["Norbert", "Br\u00fcggemann"],
- ["Christine", "Klein"],
- ["Valerija", "Dobricic"],
- ["Ana", "Westenberger"],
- ["Joanne", "Trinh"]
+ ["Joseph", "Conway"],
+ ["Yuebing", "Li"],
+ ["Sakhi", "Bhansali"]
],
- "publisher": "Neurology. Genetics",
- "issn": "2376-7839",
- "date": "2021-07-06",
- "abstract": "Our study investigated the presence of regional differences in hexanucleotide repeat number in postmortem brain tissues of 2 patients with X-linked dystonia-parkinsonism (XDP), a combined dystonia-parkinsonism syndrome modified by a (CCCTCT)",
+ "publisher": "RRNMF Neuromuscular Journal",
+ "issn": "",
+ "date": "2024-12-17",
+ "link": "https://doi.org/g8wt7z",
+ "abstract": "",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34250228"
-},
-{
- "id": "pmid:32152096",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/32152096",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:32152096']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: doi:10.17161/2tmg0f25"
},
{
- "id": "pmid:18952144",
+ "id": "doi:10.1212/NXG.0000000000200245",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/18952144",
- "title": "Genetic study of an American family with DYT3 dystonia (lubag).",
+ "title": "Redefining the Pathogenic CAG Repeat Units Threshold in\n CACNA1A\n for Spinocerebellar Ataxia Type 6",
"type": "article-journal",
- "doi": "10.1016/j.neulet.2008.10.049",
+ "doi": "10.1212/nxg.0000000000200245",
"authors": [
- ["Hao", "Deng"],
- ["Wei-Dong", "Le"],
- ["Joseph", "Jankovic"]
+ ["Yuya", "Hatano"],
+ ["Tomohiko", "Ishihara"],
+ ["Sachiko", "Hirokawa"],
+ ["Hidetoshi", "Date"],
+ ["Yuji", "Takahashi"],
+ ["Hidehiro", "Mizusawa"],
+ ["Osamu", "Onodera"]
],
- "publisher": "Neuroscience letters",
- "issn": "0304-3940",
- "date": "2008-10-21",
- "abstract": "X-linked dystonia-parkinsonism (XDP, DYT3), endemic in the Philippine island of Panay, is characterized by the clinical onset with dystonia followed by parkinsonism. We found a 35-year-old American male patient, originally from Panay with typical XDP, has a 2-year history of parkinsonism, dystonia, and tremor. Ancestral DYT3 haplotype and disease-specific SVA (short interspersed nuclear element, variable number of tandem repeats, and Alu composite) retrotransposon insertion were identified in the DYT3 proband and two female unaffected family members. No mutation(s) and expression changes in peripheral blood lymphocytes were observed in the TATA-binding protein-associated factor 1 gene (TAF1) or the chemokine CXC motif receptor 3 gene (CXCR3) of the proband or other DYT3 carriers. These findings indicate blood DNA test has a diagnostic utility and implications for genetic counseling in families with DYT3. In contrast, TAF1 and CXCR3 gene expression in peripheral blood lymphocytes is not a suitable surrogate disease marker for DYT3.",
+ "publisher": "Neurology Genetics",
+ "issn": "",
+ "date": "2025-04-01",
+ "link": "https://doi.org/g86sm6",
+ "abstract": "",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18952144"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: doi:10.1212/nxg.0000000000200245"
},
{
- "id": "pmid:18713817",
+ "id": "genereviews:NBK1333",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/18713817",
- "title": "Deoxyribonucleic acid profiling analysis of 40 human thyroid cancer cell lines reveals cross-contamination resulting in cell line redundancy and misidentification.",
- "type": "article-journal",
- "doi": "10.1210/jc.2008-1102",
+ "link": "http://www.ncbi.nlm.nih.gov/books/NBK1333/",
+ "title": "Spinal and Bulbar Muscular Atrophy",
+ "type": "chapter",
+ "doi": "",
"authors": [
- ["Rebecca E", "Schweppe"],
- ["Joshua P", "Klopper"],
- ["Christopher", "Korch"],
- ["Umarani", "Pugazhenthi"],
- ["Miriam", "Benezra"],
- ["Jeffrey A", "Knauf"],
- ["James A", "Fagin"],
- ["Laura A", "Marlow"],
- ["John A", "Copland"],
- ["Robert C", "Smallridge"],
- ["Bryan R", "Haugen"]
+ ["Albert", "La Spada"]
],
- "publisher": "The Journal of clinical endocrinology and metabolism",
- "issn": "0021-972X",
- "date": "2008-08-19",
- "abstract": "Cell lines derived from human cancers provide critical tools to study disease mechanisms and develop novel therapies. Recent reports indicate that up to 36% of cell lines are cross- contaminated.",
- "language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18713817"
+ "publisher": "GeneReviews\u00ae",
+ "issn": "",
+ "date": "1993-01-01",
+ "abstract": "Spinal and bulbar muscular atrophy (SBMA) is a gradually progressive neuromuscular disorder in which degeneration of lower motor neurons results in muscle weakness, muscle atrophy, and fasciculations in affected males. Affected individuals often show gynecomastia, testicular atrophy, and reduced fertility as a result of mild androgen insensitivity., The diagnosis of SBMA is established in a male proband by the identification of a hemizygous expansion of a CAG trinucleotide repeat (>35 CAGs) in AR by molecular genetic testing., Treatment of manifestations: Use of braces and walkers for ambulation as needed as the disease progresses; standard treatments for dysarthria and dysphagia; breast reduction surgery for gynecomastia as needed; standard treatment per cardiologist and/or endocrinologist for cardiac manifestations and metabolic syndrome; psychosocial support and education to decrease stress and burden on caregivers. Surveillance: Annual assessment of strength, mobility, activities of daily living, speech, and feeding issues; annual assessment of pulmonary function in those with advanced disease; annual assessment of cholesterol and triglycerides, with hepatic function testing if elevated; annual assessment of cardiovascular health per cardiologist; assessment of need for family and caregiver support. Other: Clinical trials of anti-androgen drugs (e.g., leuprorelin) did not consistently reveal significant efficacy, but leuprorelin was efficacious as a treatment for dysphagia in a follow-up clinical trial in Japan, leading to its approval in Japan but not elsewhere. Based on animal studies, administration of testosterone and its analogs may worsen motor neuron disease., SBMA is inherited in an X-linked manner. Affected males who are fertile pass the expanded CAG repeat to each daughter. Carrier females have a 50% chance of transmitting the CAG trinucleotide expansion to each child; males who inherit it will be affected; females who inherit it will be carriers and will usually not be affected. Carrier testing for at-risk female relatives and prenatal testing for a pregnancy at increased risk are possible if the expanded CAG repeat has been identified in an affected family member.",
+ "language": "eng",
+ "note": "PMID: 20301508\nThis CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: url:https://www.ncbi.nlm.nih.gov/books/NBK1333"
},
{
- "id": "pmid:17273961",
+ "id": "genereviews:NBK1491",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/17273961",
- "title": "Reduced neuron-specific expression of the TAF1 gene is associated with X-linked dystonia-parkinsonism.",
- "type": "article-journal",
- "doi": "10.1086/512129",
+ "link": "http://www.ncbi.nlm.nih.gov/books/NBK1491/",
+ "title": "DRPLA",
+ "type": "chapter",
+ "doi": "",
"authors": [
- ["Satoshi", "Makino"],
- ["Ryuji", "Kaji"],
- ["Satoshi", "Ando"],
- ["Maiko", "Tomizawa"],
- ["Katsuhito", "Yasuno"],
- ["Satoshi", "Goto"],
- ["Shinnichi", "Matsumoto"],
- ["Maria Daisy", "Tabuena"],
- ["Elma", "Maranon"],
- ["Marita", "Dantes"],
- ["Lillian V", "Lee"],
- ["Kazumasa", "Ogasawara"],
- ["Ikuo", "Tooyama"],
- ["Hiroyasu", "Akatsu"],
- ["Masataka", "Nishimura"],
- ["Gen", "Tamiya"]
+ ["Silvia", "Prades"],
+ ["Claudio", "Melo de Gusmao"],
+ ["Silvia", "Grimaldi"],
+ ["Yael", "Shiloh-Malawsky"],
+ ["Thomas", "Felton"],
+ ["Henry", "Houlden"]
+ ],
+ "publisher": "GeneReviews\u00ae",
+ "issn": "",
+ "date": "1993-01-01",
+ "abstract": "DRPLA (dentatorubral-pallidoluysian atrophy) is a progressive neurologic disorder characterized by five cardinal features (irrespective of the age of onset): ataxia, cognitive decline, myoclonus, chorea, epilepsy, and psychiatric manifestations. Onset ranges from infancy to late adulthood (range: age 0-72 years; mean: age 31.5 years). The clinical presentation varies by age of onset: individuals with juvenile onset (before age 20 years) have myoclonus, epilepsy, and progressive intellectual deterioration, whereas individuals with adult onset (after age 20 years) have ataxia, choreoathetosis, and dementia or neuropsychiatric changes. Disease duration is on average eight years (range: 0-35 years) and age at death is on average 49 years (range: age 18-80 years)., The diagnosis of DRPLA is established in a proband with suggestive clinical findings and a heterozygous pathogenic CAG trinucleotide expansion in ATN1 identified by molecular genetic testing., Treatment of manifestations: Standard anti-seizure medications (ASMs) for seizures; appropriate psychotropic medications for psychiatric manifestations; symptomatic treatment of ataxia with riluzole and rehabilitation therapy; adaptation of environment and care to the level of dementia; appropriate educational programs for children. Agents/circumstances to avoid: General anesthesia can increase the risk of intra- and postoperative seizures. Pregnancy management: Because the use of ASMs during pregnancy may have an effect on the fetus, discussion of the risks and benefits of using an ASM during pregnancy should ideally occur prior to conception when transition to a lower-risk medication may be possible. The use of riluzole during pregnancy has not been well studied in humans., DRPLA is inherited in an autosomal dominant manner. The risk to the children of an affected individual of inheriting an expanded CAG repeat is 50%. The size of the repeat transmitted to the offspring depends on the size of the parent's repeat and the sex of the transmitting parent. Once an abnormal CAG repeat expansion in ATN1 has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.",
+ "language": "eng",
+ "note": "PMID: 20301664\nThis CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: url:https://www.ncbi.nlm.nih.gov/books/NBK1491"
+},
+{
+ "id": "genereviews:NBK1184",
+ "manubot_success": true,
+ "link": "http://www.ncbi.nlm.nih.gov/books/NBK1184/",
+ "title": "Spinocerebellar Ataxia Type 1",
+ "type": "chapter",
+ "doi": "",
+ "authors": [
+ ["Puneet", "Opal"],
+ ["Tetsuo", "Ashizawa"]
+ ],
+ "publisher": "GeneReviews\u00ae",
+ "issn": "",
+ "date": "1993-01-01",
+ "abstract": "Spinocerebellar ataxia type 1 (SCA1) is characterized by progressive cerebellar ataxia, dysarthria, and eventual deterioration of bulbar functions. Early in the disease, affected individuals may have gait disturbance, slurred speech, difficulty with balance, brisk deep tendon reflexes, hypermetric saccades, nystagmus, and mild dysphagia. Later signs include slowing of saccadic velocity, development of upgaze palsy, dysmetria, dysdiadochokinesia, and hypotonia. In advanced stages, muscle atrophy, decreased deep tendon reflexes, loss of proprioception, cognitive impairment (e.g., frontal executive dysfunction, impaired verbal memory), chorea, dystonia, and bulbar dysfunction are seen. Onset is typically in the third or fourth decade, although childhood onset and late-adult onset have been reported. Those with onset after age 60 years may manifest a pure cerebellar phenotype. Interval from onset to death varies from ten to 30 years; individuals with juvenile onset show more rapid progression and more severe disease. Anticipation is observed. An axonal sensory neuropathy detected by electrophysiologic testing is common; brain imaging typically shows cerebellar and brain stem atrophy., The diagnosis of SCA1 is established in a proband with characteristic clinical findings and an abnormal CAG repeat expansion in ATXN1 identified by molecular genetic testing. Affected individuals usually have 39 or more CAG repeats., Treatment of manifestations: Supportive care including adaptive devices, physical therapy, occupational therapy, avoidance of obesity; intensive rehabilitation (coordinative physiotherapy) may be beneficial; speech therapy and communication devices for dysarthria; video esophagram to help identify the consistency of food least likely to trigger aspiration and feeding devices may be indicated with recurrent aspiration; caloric support for those with weight loss; vitamin supplementation as needed; psychotherapy, neuropsychologic rehabilitation, and/or standard psychiatric treatments for cognitive and psychiatric manifestations; pharmacotherapy and/or referral to pain management as needed for pain. Surveillance: Every three to six months: neurologic assessment for progression of ataxia, and physiatry, occupational therapy, and physical therapy assessment for mobility and self-help skills; at each visit: assessment of access to communication, speech needs, aspiration risk, feeding needs, mood, psychiatric manifestations, cognition, and family needs. Agents/circumstances to avoid: Alcohol, medications known to cause nerve damage (e.g., isoniazid, large-dose vitamin B6), and circumstances that could lead to physical harm, such as operating machinery or climbing to great heights., SCA1 is inherited in an autosomal dominant manner. Offspring of an affected individual have a 50% chance of inheriting the expanded allele. Anticipation has been observed in SCA1; expansions are more likely to occur when the pathogenic ATXN1 allele is paternally transmitted, and contractions are more typical of maternal transmissions. Once an abnormal CAG trinucleotide expansion in ATXN1 has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.",
+ "language": "eng",
+ "note": "PMID: 20301363\nThis CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: url:https://www.ncbi.nlm.nih.gov/books/NBK1184"
+},
+{
+ "id": "genereviews:NBK1196",
+ "manubot_success": true,
+ "link": "http://www.ncbi.nlm.nih.gov/books/NBK1196/",
+ "title": "Spinocerebellar Ataxia Type 3",
+ "type": "chapter",
+ "doi": "",
+ "authors": [
+ ["Henry", "Paulson"],
+ ["Vikram", "Shakkottai"]
],
- "publisher": "American journal of human genetics",
- "issn": "0002-9297",
- "date": "2007-01-23",
- "abstract": "X-linked dystonia-parkinsonism (XDP) is a movement disorder endemic to the Philippines. The disease locus, DYT3, has been mapped to Xq13.1. In a search for the causative gene, we performed genomic sequencing analysis, followed by expression analysis of XDP brain tissues. We found a disease-specific SVA (short interspersed nuclear element, variable number of tandem repeats, and Alu composite) retrotransposon insertion in an intron of the TATA-binding protein-associated factor 1 gene (TAF1), which encodes the largest component of the TFIID complex, and significantly decreased expression levels of TAF1 and the dopamine receptor D2 gene (DRD2) in the caudate nucleus. We also identified an abnormal pattern of DNA methylation in the retrotransposon in the genome from the patient's caudate, which could account for decreased expression of TAF1. Our findings suggest that the reduced neuron-specific expression of the TAF1 gene is associated with XDP.",
- "language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17273961"
+ "publisher": "GeneReviews\u00ae",
+ "issn": "",
+ "date": "1993-01-01",
+ "abstract": "Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is characterized by progressive cerebellar ataxia and variable findings including pyramidal signs, a dystonic-rigid extrapyramidal syndrome, significant peripheral amyotrophy and generalized areflexia, progressive external ophthalmoplegia, action-induced facial and lingual fasciculations, and bulging eyes. Neurologic findings tend to evolve as the disorder progresses., The diagnosis of SCA3 is established in a proband with suggestive findings and a heterozygous abnormal CAG trinucleotide repeat expansion in ATXN3 identified by molecular genetic testing., Treatment of manifestations: Management is supportive as no medication slows the course of disease. The goals of treatment are to maximize function and reduce complications. It is recommended that each individual be managed by a multidisciplinary team of relevant specialists such as neurologists, occupational therapists, physical therapists, physiatrists, orthopedists, nutritionists, speech therapists, social workers, and psychologists. Various manifestations may respond to pharmacologic agents. Regular physical activity is recommended, including combined physical and occupational therapy focused on gait and coordination. Canes and walkers help prevent falling; motorized scooters, weighted eating utensils, and dressing hooks help to maintain independence. Speech therapy and communication devices may benefit those with dysarthria, and dietary modification those with dysphagia. Other recommendations include home adaptations to prevent falls and improve mobility, dietary supplements if caloric intake is reduced, weight control to facilitate ambulation and mobility, and caution with general anesthesia. Surveillance: Annual assessments (or more frequently as needed) of neurologic findings (e.g., dysarthria, dysphagia, bladder dysfunction, neuropathic pain, cognitive and psychiatric manifestations), weight and nutritional status, and social support., SCA3 is inherited in an autosomal dominant manner. Each child of an affected individual has a 50% chance of inheriting the ATXN3 CAG repeat expansion. Once the CAG repeat expansion has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible. Note: The prenatal finding of an ATXN3 CAG repeat expansion cannot be used to accurately predict onset, severity, type of symptoms, or rate of progression of SCA3.",
+ "language": "eng",
+ "note": "PMID: 20301375\nThis CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: url:https://www.ncbi.nlm.nih.gov/books/NBK1196"
},
{
- "id": "pmid:7668293",
+ "id": "genereviews:NBK1268",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/7668293",
- "title": "Assignment of the dystonia-parkinsonism syndrome locus, DYT3, to a small region within a 1.8-Mb YAC contig of Xq13.1.",
- "type": "article-journal",
+ "link": "http://www.ncbi.nlm.nih.gov/books/NBK1268/",
+ "title": "Spinocerebellar Ataxia Type 8",
+ "type": "chapter",
"doi": "",
"authors": [
- ["G", "Haberhausen"],
- ["I", "Schmitt"],
- ["A", "K\u00f6hler"],
- ["U", "Peters"],
- ["S", "Rider"],
- ["J", "Chelly"],
- ["J D", "Terwilliger"],
- ["A P", "Monaco"],
- ["U", "M\u00fcller"]
+ ["John Douglas", "Cleary"],
+ ["S. H.", "Subramony"],
+ ["Laura PW", "Ranum"]
],
- "publisher": "American journal of human genetics",
- "issn": "0002-9297",
- "date": "1995-09-01",
- "abstract": "A YAC contig was constructed of Xq13.1 in order to sublocalize the X-linked dystonia-parkinsonism (XDP) syndrome locus, DYT3. The contig spans a region of approximately 1.8 Mb and includes loci DXS453/DXS348/IL2R gamma/GJB1/CCG1/DXS559. For the construction of the contig, nine sequence-tagged sites and four short tandem repeat polymorphisms (STRPs) were isolated. The STRPs, designated as 4704#6 (DXS7113), 4704#7 (DXS7114), 67601 (DXS7117), and B4Pst (DXS7119) were assigned to a region flanked by DXS348 proximally and by DXS559 distally. Their order was DXS348/4704 #6/4704 #7/67601/B4Pst/DXS559. They were applied to the analysis of allelic association and of haplotypes in 47 not-obviously-related XDP patients and in 105 Filipino male controls. The same haplotype was found at loci 67601 (DXS7117) and B4Pst (DXS7119) in 42 of 47 patients. This percentage of common haplotypes decreased at the adjacent loci. The findings, together with the previous demonstration of DXS559 being the distal flanking marker of DYT3, assign the disease locus to a small region in Xq13.1 defined by loci 67601 (DXS7117) and B4Pst (DXS7119). The location of DYT3 was born out by the application of a newly developed likelihood method for the analysis of linkage disequilibrium.",
- "language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7668293"
+ "publisher": "GeneReviews\u00ae",
+ "issn": "",
+ "date": "1993-01-01",
+ "abstract": "SCA8 is a slowly progressive ataxia with onset typically in the third to fifth decade but with a range from before age one year to after age 60 years. Common initial manifestations are scanning dysarthria with a characteristic drawn-out slowness of speech and gait instability. Over the disease course other findings can include eye movement abnormalities (nystagmus, abnormal pursuit and abnormal saccades, and, rarely, ophthalmoplegia); upper motor neuron involvement; extrapyramidal signs; brain stem signs (dysphagia and poor cough reflex); sensory neuropathy; and cognitive impairment (e.g., executive dysfunction, psychomotor slowing and other features of cerebellar cognitive-affective disorder in some). Life span is typically not shortened., The diagnosis of SCA8 is established in a proband with suggestive findings and a heterozygous abnormal (CTG\u00b7CAG)n repeat expansion in the two overlapping genes ATXN8OS/ATXN8 identified by molecular genetic testing., Treatment of manifestations: Canes and walkers to help prevent falls; modification of the home (e.g., grab bars, raised toilet seats, ramps for motorized chairs) as needed; speech therapy and communication devices for those with dysarthria; weighted eating utensils and dressing hooks to maintain some independence; feeding evaluations to reduce risk of aspiration from dysphagia; physical activity to maintain muscular and cardiopulmonary conditioning. Surveillance: Routine follow up by the multidisciplinary care team including neurology to assess disease progression; physiatry and occupational and physical therapy to assess mobility and self-help skills; speech and language specialists to assess need for alternative communication method or speech therapy; feeding team to assess nutrition, aspiration risk, and feeding methods; and mental health professionals. Agents/circumstances to avoid: Alcohol can exacerbate incoordination., SCA8 is inherited in an autosomal dominant manner with reduced penetrance. To date, all individuals diagnosed with SCA8 whose parents have been evaluated with molecular genetic testing have one parent with an ATXN8OS/ATXN8 (CTG\u00b7CAG)n repeat expansion. The transmitting parent may or may not have clinical manifestations of SCA8. If a parent of the proband is known to have a (CTG\u00b7CAG)n repeat expansion, the risk to each sib of inheriting the repeat expansion is 50%. The (CTG\u00b7CAG)n repeat expansion is highly unstable and almost always changes in size on transmission: the repeat expansion is more likely to become larger when maternally transmitted and more likely to contract with paternal transmission. Sibs who inherit a (CTG\u00b7CAG)n repeat expansion may or may not develop clinical manifestations of SCA8. Once an SCA8 (CTG\u00b7CAG)n repeat expansion has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.",
+ "language": "eng",
+ "note": "PMID: 20301445\nThis CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: url:https://www.ncbi.nlm.nih.gov/books/NBK1268"
},
{
- "id": "pmid:1518853",
+ "id": "genereviews:NBK268647",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/1518853",
- "title": "Delineation of the dystonia-parkinsonism syndrome locus in Xq13.",
- "type": "article-journal",
- "doi": "10.1073/pnas.89.17.8245",
+ "link": "http://www.ncbi.nlm.nih.gov/books/NBK268647/",
+ "title": "C9orf72 Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis",
+ "type": "chapter",
+ "doi": "",
"authors": [
- ["M B", "Graeber"],
- ["K G", "Kupke"],
- ["U", "M\u00fcller"]
+ ["Helena", "Gossye"],
+ ["Sebastiaan", "Engelborghs"],
+ ["Christine", "Van Broeckhoven"],
+ ["Julie", "Zee"]
],
- "publisher": "Proceedings of the National Academy of Sciences of the United States of America",
- "issn": "0027-8424",
- "date": "1992-09-01",
- "abstract": "The X chromosome-linked dystonia-parkinsonism syndrome (XDP) is a severe movement disorder, characterized by both dystonia and parkinsonism. XDP is a genetically homogeneous disorder. Known ancestry of all patients has been traced back to Panay, Philippines, where the disease probably originated from a single mutation (founder effect). The gene locus, DYT3, has been previously assigned to the proximal long arm of the X chromosome (Xq12-q21.1). Using four dinucleotide tandem repeat (DNTR) sequences from Xq13-derived yeast artificial chromosomes (YACs), we further delineate DYT3 within Xq13. Observation of a recombination event between DYT3 and DNTR locus 4548-7, derived from a YAC encompassing locus DXS56, establishes 4548-7 as a distal flanking marker. Assignment of DYT3 to a region in Xq13, flanked by loci 4548-7 and DXS159, is further supported by highly significant allelic association between DYT3 and a total of four DNTR loci--PY2-31, PY5-10, 4548-1, and 4548-7--located in a region defined by PGK1 and DXS56. /phi/ and /delta/ values were 0.82/0.35, 0.78/0.42, 0.65/0.34, and 0.88/0.58 for PY2-31, PY5-10, 4548-1, and 4548-7 at P less than 10(-2), P less than 10(-4), P less than 10(-3), and P less than 10(-6).",
- "language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:1518853"
+ "publisher": "GeneReviews\u00ae",
+ "issn": "",
+ "date": "1993-01-01",
+ "abstract": "C9orf72 frontotemporal dementia and/or amyotrophic lateral sclerosis (C9orf72-FTD/ALS) is characterized most often by frontotemporal dementia (FTD) and upper and lower motor neuron disease (MND); however, atypical presentations also occur. Age at onset is usually between 50 and 64 years (range: 20-91 years) irrespective of the presenting manifestations, which may be pure FTD, pure amyotrophic lateral sclerosis (ALS), or a combination of the two phenotypes. The clinical presentation is highly heterogeneous and may differ between and within families, causing an unpredictable pattern and age of onset of clinical manifestations. The presence of MND correlates with an earlier age of onset and a worse overall prognosis., The diagnosis of C9orf72-FTD/ALS is established in a proband with suggestive findings and a heterozygous abnormal G4C2 (GGGGCC) hexanucleotide repeat expansion in C9orf72 identified by molecular genetic testing., Treatment of manifestations: Care is often provided by a multidisciplinary team that includes a neurologist, specially trained nurses, pulmonologist, speech therapist, physical therapist, occupational therapist, respiratory therapist, nutritionist, psychologist, social worker, and genetic counselor. Surveillance: Routine follow up by multidisciplinary specialists to monitor neurologic findings, mobility and activities of daily living, psychiatric/behavioral manifestations, nutrition and safety of oral feeding, respiratory and bladder function, and needs of affected individuals and care providers for psychosocial support., C9orf72-FTD/ALS is inherited in an autosomal dominant manner. Almost all individuals diagnosed with C9orf72-FTD/ALS inherited a C9orf72 G4C2 repeat expansion from a heterozygous parent. In most families the heterozygous parent is affected; however, a heterozygous parent may not have clinical manifestations of the disorder due to age-dependent reduced penetrance. Each child of an individual with C9orf72-FTD/ALS has a 50% chance of inheriting the C9orf72 G4C2 repeat expansion. Once a C9orf72 G4C2 repeat expansion has been identified in an affected family member, prenatal and preimplantation genetic testing for the presence of the C9orf72 G4C2 repeat expansion are possible. (Note: The presence of a C9orf72 G4C2 repeat expansion cannot predict the disease course in any given individual.)",
+ "language": "eng",
+ "note": "PMID: 25577942\nThis CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: url:https://www.ncbi.nlm.nih.gov/books/NBK268647"
},
{
- "id": "pmid:39680235",
+ "id": "genereviews:NBK1466",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/39680235",
- "title": "Case Series of Cerebellar Ataxia with Tremor Due to Heterozygous STUB1 Variants (SCA48) without TBP Expansions: Further Evidence for SCA48 as a Monogenic Disease.",
- "type": "article-journal",
- "doi": "10.1007/s12311-024-01762-2",
+ "link": "http://www.ncbi.nlm.nih.gov/books/NBK1466/",
+ "title": "Myotonic Dystrophy Type 2",
+ "type": "chapter",
+ "doi": "",
"authors": [
- ["Yan", "Zochowski"],
- ["Kishore R", "Kumar"],
- ["Matthew", "Katz"],
- ["Paul", "Darveniza"],
- ["Michel", "Tchan"],
- ["Renee", "Smyth"],
- ["Susan", "Tomlinson"],
- ["Kathy H C", "Wu"],
- ["Stephen", "Tisch"]
+ ["Benedikt", "Schoser"]
],
- "publisher": "Cerebellum (London, England)",
- "issn": "1473-4230",
- "date": "2024-12-16",
- "abstract": "Clinically-relevant variants in the STUB1 gene have been associated with an autosomal dominant spinocerebellar ataxia 48 (SCA48), a recently described inherited neurodegenerative condition that is characterised by cognitive and psychiatric changes. To describe the clinical phenotype and genetic findings of three new Australian probands with STUB1 to expand the current understanding of the spectrum of clinical presentation and natural history of SCA48. Clinical and genetic review of patients diagnosed with SCA48 ataxia drawn from our centres. The third case was derived from a collaborating centre (Royal Brisbane Hospital). We identified three unrelated SCA48 patients with heterozygous pathogenic STUB1 variants. All presented with slowly progressive cerebellar ataxia with tremor and additional findings of dysarthria, parkinsonism, hypertonia, cognitive and psychiatric symptoms. Age of onset varied from 34 to 65 years of age. Brain MRI showed significant diffuse cerebellar atrophy, affecting the vermis and cerebellar hemispheres. We identified two novel pathogenic variants of STUB1 gene, and one previously reported pathogenic variant. Genetic testing for intermediate expansions of TBP (SCA17) identified TBP repeats within the normal range of 25-40 in all 3 probands. Our case series expands the clinical spectrum of SCA48. We highlight the importance of tremor as part of the clinical phenotype including upper limb rest tremor and Parkinsonian signs. Our cases lacked pathological TBP expansions and provide additional evidence that STUB1 (SCA48) can manifest as a monogenic disease.",
- "language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39680235"
+ "publisher": "GeneReviews\u00ae",
+ "issn": "",
+ "date": "1993-01-01",
+ "abstract": "Myotonic dystrophy type 2 (DM2) is characterized by myotonia and muscle dysfunction (proximal and axial weakness, myalgia, and stiffness), and less commonly by posterior subcapsular cataracts, cardiac conduction defects, insulin-insensitive type 2 diabetes mellitus, and other endocrine abnormalities. While myotonia (involuntary muscle contraction with delayed relaxation) has been reported during the first decade, onset is typically in the third to fourth decade, most commonly with fluctuating or episodic muscle pain that can be debilitating and proximal and axial weakness of the neck flexors and the hip flexors. Subsequently, weakness occurs in the elbow extensors and finger flexors. Facial weakness and weakness of the ankle dorsiflexors are less common. Myotonia rarely causes severe symptoms. In a subset of individuals, calf hypertrophy in combination with brisk reflexes is notable., The diagnosis of DM2 is established in a proband by identification of a heterozygous pathogenic expansion of a CCTG repeat within a complex repeat motif, (TG)n(TCTG)n(CCTG)n in CNBP. The number of CCTG repeats in a pathogenic expansion ranges from approximately 75 to more than 11,000, with a mean of approximately 5,000 repeats. The detection rate of a CNBP CCTG expansion is more than 99% with the combination of routine PCR, Southern blot analysis, and the PCR repeat-primed assay., Treatment of manifestations: Ankle-foot orthoses, wheelchairs, or other assistive devices as needed for weakness; routine physical activity appears to help maintain muscle strength and endurance and to control musculoskeletal pain; medications used with some success in myalgia management include mexilitene, gabapentin, pregabalin, nonsteroidal anti-inflammatory drugs, low-dose thyroid replacement, and tricyclic antidepressants; myotonia rarely requires treatment but mexilitene or lamotrigine may be beneficial in some individuals; removal of cataracts or epiretinal membrane that impair vision; defibrillator placement for those with arrhythmias; hormone substitution therapy for endocrine dysfunction; prokinetic agents may be helpful for gastrointestinal manifestations; cognitive behavioral therapy and modafinil may be helpful for fatigue and daytime sleepiness; vitamin D supplementation for those with deficiency; hearing aids for sensorineural hearing loss. Prevention of secondary complications: Anesthetic risk may be increased and therefore assessment of cardiac and respiratory function before and after surgery are recommended. Prompt treatment of hypothyroidism and vitamin D deficiency to reduce secondary weakness and myotonia. Surveillance: Annual evaluation with neurologist, occupational therapist, and physical therapist; annual ophthalmology evaluation for posterior subcapsular cataracts and epiretinal membranes; annual EKG, echocardiogram, and 24-hour Holter monitoring to detect/monitor cardiac conduction defects and cardiomyopathy; cardiac MRI per cardiologist; annual measurement of fasting serum glucose concentration, glycosylated hemoglobin level, thyroid hormone levels, and vitamin D; serum testosterone and FSH per endocrinologist. Agents/circumstances to avoid: Cholesterol-lowering medications when associated with increased weakness., DM2 is inherited in an autosomal dominant manner. To date, all individuals whose biological parents have been evaluated with molecular genetic testing have had one parent with a CCTG repeat expansion; de novo pathogenic variants have not been reported. Each child of an individual with a CCTG repeat expansion has a 50% chance of inheriting the expansion. There is no correlation between disease severity and CCTG repeat length. Prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible once the CCTG repeat expansion has been identified in an affected family member.",
+ "language": "eng",
+ "note": "PMID: 20301639\nThis CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: url:https://www.ncbi.nlm.nih.gov/books/NBK1466"
},
{
- "id": "pmid:39125760",
+ "id": "genereviews:NBK1119",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/39125760",
- "title": "The New Face of Dynamic Mutation-The CAA [CAG]n CAA CAG Motif as a Mutable Unit in the",
- "type": "article-journal",
- "doi": "10.3390/ijms25158190",
+ "link": "http://www.ncbi.nlm.nih.gov/books/NBK1119/",
+ "title": "Dystrophinopathies",
+ "type": "chapter",
+ "doi": "",
"authors": [
- ["Dorota", "Hoffman-Zacharska"],
- ["Anna", "Sulek"]
+ ["Basil T.", "Darras"],
+ ["David K.", "Urion"],
+ ["Partha S.", "Ghosh"]
],
- "publisher": "International journal of molecular sciences",
- "issn": "1422-0067",
- "date": "2024-07-26",
- "abstract": "Since 1991, several genetic disorders caused by unstable trinucleotide repeats (TNRs) have been identified, collectively referred to as triplet repeat diseases (TREDs). They share a common mutation mechanism: the expansion of repeats (dynamic mutations) due to the propensity of repeated sequences to form unusual DNA structures during replication. TREDs are characterized as neurodegenerative diseases or complex syndromes with significant neurological components. Spinocerebellar ataxia type 17 (SCA17) falls into the former category and is caused by the expansion of mixed CAA/CAG repeats in the",
- "language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39125760"
+ "publisher": "GeneReviews\u00ae",
+ "issn": "",
+ "date": "1993-01-01",
+ "abstract": "The dystrophinopathies cover a spectrum of X-linked muscle disease ranging from mild to severe that includes Duchenne muscular dystrophy, Becker muscular dystrophy, and DMD-associated dilated cardiomyopathy (DCM). The mild end of the spectrum includes the phenotypes of asymptomatic increase in serum concentration of creatine phosphokinase (CK) and muscle cramps with myoglobinuria. The severe end of the spectrum includes progressive muscle diseases that are classified as Duchenne/Becker muscular dystrophy when skeletal muscle is primarily affected and as DMD-associated DCM when the heart is primarily affected. Duchenne muscular dystrophy (DMD) usually presents in early childhood with delayed motor milestones including delays in walking independently and standing up from a supine position. Proximal weakness causes a waddling gait and difficulty climbing stairs, running, jumping, and standing up from a squatting position. DMD is rapidly progressive, with affected children being wheelchair dependent by age 12 years. Cardiomyopathy occurs in almost all individuals with DMD after age 18 years. Few survive beyond the third decade, with respiratory complications and progressive cardiomyopathy being common causes of death. Becker muscular dystrophy (BMD) is characterized by later-onset skeletal muscle weakness. With improved diagnostic techniques, it has been recognized that the mild end of the spectrum includes men with onset of symptoms after age 30 years who remain ambulatory even into their 60s. Despite the milder skeletal muscle involvement, heart failure from DCM is a common cause of morbidity and the most common cause of death in BMD. Mean age of death is in the mid-40s. DMD-associated DCM is characterized by left ventricular dilatation and congestive heart failure. Females heterozygous for a DMD pathogenic variant are at increased risk for DCM., The diagnosis of a dystrophinopathy is established in a proband with the characteristic clinical findings and elevated CK concentration and/or by identification of a hemizygous pathogenic variant in DMD on molecular genetic testing in a male and of a heterozygous pathogenic variant in DMD on molecular genetic testing in a female. Females may present with a classic dystrophinopathy or may be asymptomatic carriers., Treatment of manifestations: ACE inhibitors are used with or without beta blockers for cardiomyopathy in both DMD and BMD phenotypes. Congestive heart failure is treated with diuretics and oxygen as needed; cardiac transplantation is offered to persons with severe dilated cardiomyopathy and BMD with limited or no clinical evidence of skeletal muscle disease. Scoliosis is treated with bracing and surgery. Corticosteroid therapy improves muscle strength and function for individuals with DMD between ages five and 15 years; the same treatment is used in BMD, although the efficacy is less clear. Dystrophin restoration therapies have been developed by using synthetic antisense oligonucleotides to restore the reading frame by exon skipping for individuals with specific pathogenic variants in DMD. Prevention of secondary complications: Evaluation by a pulmonologist and cardiologist before surgeries; pneumococcal and influenza immunizations annually; nutrition assessment; physical therapy to promote mobility and prevent contractures; sunshine and a balanced diet rich in vitamin D and calcium to improve bone density and reduce the risk of fractures; weight control to avoid obesity. Surveillance: For males with DMD or BMD: annual or biannual evaluation by a cardiologist beginning at the time of diagnosis; monitoring for scoliosis; baseline pulmonary function testing before wheelchair dependence; frequent evaluations by a pediatric pulmonologist. For heterozygous females: cardiac evaluation at least once after the teenage years. Agents/circumstances to avoid: Botulinum toxin injections; succinylcholine and inhalational anesthetics because of susceptibility to malignant hyperthermia or malignant hyperthermia-like reactions. Evaluation of relatives at risk: Early identification of heterozygous females who are at increased risk for cardiomyopathy and, thus, need routine cardiac surveillance and prompt treatment., The dystrophinopathies are inherited in an X-linked manner. The risk to the sibs of a proband depends on the genetic status of the mother. Heterozygous females have a 50% chance of transmitting the DMD pathogenic variant in each pregnancy. Sons who inherit the pathogenic variant will be affected; daughters who inherit the pathogenic variant are heterozygous and may have a range of clinical manifestations. Males with DMD usually do not reproduce. Males with BMD or DMD-associated DCM may reproduce: all of their daughters are heterozygotes; none of their sons inherit their father's DMD pathogenic variant. Carrier testing for at-risk females, prenatal testing, and preimplantation genetic testing are possible if the DMD pathogenic variant in the family is known.",
+ "language": "eng",
+ "note": "PMID: 20301298\nThis CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: url:https://www.ncbi.nlm.nih.gov/books/NBK1119"
},
{
- "id": "pmid:38494459",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/38494459",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:38494459']' timed out after 3 seconds"
+ "id": "genereviews:NBK1165",
+ "manubot_success": true,
+ "link": "http://www.ncbi.nlm.nih.gov/books/NBK1165/",
+ "title": "Myotonic Dystrophy Type 1",
+ "type": "chapter",
+ "doi": "",
+ "authors": [
+ ["Thomas D.", "Bird"]
+ ],
+ "publisher": "GeneReviews\u00ae",
+ "issn": "",
+ "date": "1993-01-01",
+ "abstract": "Myotonic dystrophy type 1 (DM1) is a multisystem disorder that affects skeletal and smooth muscle as well as the eye, heart, endocrine system, and central nervous system. The clinical findings, which span a continuum from mild to severe, have been categorized into three somewhat overlapping phenotypes: mild, classic, and congenital. Mild DM1 is characterized by cataract and mild myotonia (sustained muscle contraction); life span is normal. Classic DM1 is characterized by muscle weakness and wasting, myotonia, cataract, and often cardiac conduction abnormalities; adults may become physically disabled and may have a shortened life span. Congenital DM1 is characterized by hypotonia and severe generalized weakness at birth, often with respiratory insufficiency and early death; intellectual disability is common., DM1 is caused by expansion of a CTG trinucleotide repeat in the noncoding region of DMPK. The diagnosis of DM1 is suspected in individuals with characteristic muscle weakness and is confirmed by molecular genetic testing of DMPK. CTG repeat length exceeding 34 repeats is abnormal. Molecular genetic testing detects pathogenic variants in nearly 100% of affected individuals., Treatment of manifestations: Use of ankle-foot orthoses, wheelchairs, or other assistive devices; special education support for affected children; treatment of hypothyroidism; management of pain; consultation with a cardiologist for symptoms or EKG evidence of arrhythmia; removal of cataracts if vision is impaired; hormone replacement therapy for males with hypogonadism; surgical excision of pilomatrixoma and basal cell carcinomas. Prevention of secondary complications: Choice of induction agents, airway care, local anesthesia, and neuromuscular blockade to minimize complications during surgery; cardiac pacemakers or implantable cardioverter-defibrillators may prevent life-threatening arrhythmias; continue physical activity and maintain appropriate weight. Surveillance: Annual EKG or 24-hour Holter monitoring; annual measurement of fasting serum glucose concentration and glycosylated hemoglobin concentration; ophthalmology examination every two years; attention to nutritional status; polysomnography for sleep disturbances. Agents/circumstances to avoid: Cholesterol-lowering medications (i.e., statins), which can cause muscle pain and weakness; the anesthetic agent vecuronium; succinylcholine, propofol, and doxorubicin; smoking; obesity; illicit drug use; excessive alcohol intake. Evaluation of relatives at risk: Molecular genetic testing for early diagnosis of relatives at risk to allow treatment of cardiac manifestations, diabetes mellitus, and cataracts., DM1 is inherited in an autosomal dominant manner. Offspring of an affected individual have a 50% chance of inheriting the expanded allele. Pathogenic alleles may expand in length during gametogenesis, resulting in the transmission of longer trinucleotide repeat alleles that may be associated with earlier onset and more severe disease than that observed in the parent. Prenatal testing and preimplantation genetic testing are possible when the diagnosis of DM1 has been confirmed by molecular genetic testing in an affected family member.",
+ "language": "eng",
+ "note": "PMID: 20301344\nThis CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: url:https://www.ncbi.nlm.nih.gov/books/NBK1165"
},
{
- "id": "pmid:37632648",
+ "id": "genereviews:NBK599589",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/37632648",
- "title": "A DLB patient with complicated CAA interruptions and intermediate alleles of 43 CAG/CAA repeats in TBP.",
- "type": "article-journal",
- "doi": "10.1007/s13760-023-02351-6",
+ "link": "http://www.ncbi.nlm.nih.gov/books/NBK599589/",
+ "title": "GAA-FGF14-Related Ataxia",
+ "type": "chapter",
+ "doi": "",
"authors": [
- ["Zhiru", "Lin"],
- ["Jiaxiang", "Li"],
- ["Wei", "Luo"]
+ ["David", "Pellerin"],
+ ["Matt", "Danzi"],
+ ["Mathilde", "Renaud"],
+ ["Henry", "Houlden"],
+ ["Matthis", "Synofzik"],
+ ["Stephan", "Zuchner"],
+ ["Bernard", "Brais"]
],
- "publisher": "Acta neurologica Belgica",
- "issn": "2240-2993",
- "date": "2023-08-26",
- "abstract": "",
- "language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37632648"
+ "publisher": "GeneReviews\u00ae",
+ "issn": "",
+ "date": "1993-01-01",
+ "abstract": "GAA-FGF14-related ataxia is a mid to late adult-onset slowly progressive cerebellar syndrome with predominant gait involvement. Median age at onset is 60 years (range: 21-87 years). Nearly 50% of individuals may first experience episodic manifestations including gait and limb ataxia, visual disturbances (diplopia, oscillopsia, and blurring), vertigo and/or dizziness, or dysarthria on average two to four years before the onset of progressive ataxia. Episodic symptoms may persist after the onset of progressive ataxia and may be triggered by alcohol intake and physical activity. Although some individuals eventually require assistance with mobility, use of a wheelchair is less necessary than in other common hereditary spinocerebellar ataxias (e.g., SCA1, SCA2, and SCA3). Dysarthria does not develop in all individuals and often remains mild to moderate. Cerebellar oculomotor signs, including downbeat nystagmus, horizontal gaze-evoked nystagmus, and impaired visual fixation suppression of the vestibuloocular reflex, are common. Unilateral or bilateral vestibular hypofunction and tremor of the upper limbs may occur. Age of onset and clinical presentation can vary within the same family., The diagnosis of GAA-FGF14-related ataxia is established in a symptomatic individual with a compatible phenotype by the identification of a heterozygous (GAA)>300 repeat expansion in intron 1 of FGF14 by molecular genetic testing. Due to reduced penetrance of FGF14 (GAA)250-300 repeat expansions, the diagnosis of GAA-FGF14-related ataxia can also be established in symptomatic individuals with a (GAA)250-300 repeat expansion if their phenotype is compatible, other inherited causes of ataxia have been excluded, and, if possible, familial segregation with the disease is confirmed. Individuals whose phenotype differs significantly from GAA-FGF14-related ataxia should be screened for other causes of inherited ataxias., Treatment of manifestations: There is no cure for GAA-FGF14-related ataxia. The goals of treatment are to improve quality of life, maximize function, and reduce complications. This ideally involves multidisciplinary care by specialists in relevant fields, such as neurologists, ophthalmologists, orthoptists, physical therapists, occupational therapists, speech-language therapists, and psychologists. Preliminary studies have shown promising symptomatic benefits of 4-aminopyridine for ataxic symptoms and downbeat nystagmus. Surveillance: To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, regularly scheduled follow up by the treating specialists is recommended. Agents/circumstances to avoid: Inform affected individuals that alcohol intake and strenuous physical activity may precipitate episodes of ataxia and may exacerbate incoordination. Avoid medications with known toxicity to the cerebellum and the vestibular system., GAA-FGF14-related ataxia is inherited in an autosomal dominant manner. Most individuals diagnosed with GAA-FGF14-related ataxia inherit an abnormal GAA repeat expansion from a parent who has a high normal-size or likely pathogenic or pathogenic GAA repeat expansion (a parent with an abnormal GAA repeat expansion may or may not have manifestations of GAA-FGF14-related ataxia). Each child of an individual with GAA-FGF14-related ataxia has a 50% chance of inheriting the GAA-FGF14-related allele. The likelihood that offspring who inherit the GAA-FGF14-related allele will have a GAA repeat size in the pathogenic, reduced penetrance, or non-pathogenic range is influenced by intergenerational instability; the size of the GAA repeat is more likely to expand upon maternal transmission and to contract upon paternal transmission. Once a GAA repeat expansion has been identified in an affected family member, predictive testing for at-risk relatives and prenatal and preimplantation genetic testing for GAA-FGF14-related ataxia are possible. However, accurate prediction of future possible clinical manifestations in a fetus found to have an FGF14 GAA repeat expansion is not possible, and the current lack of knowledge regarding somatic instability of the repeat prenatally makes the interpretation of prenatal genetic test results challenging.",
+ "language": "eng",
+ "note": "PMID: 38271551\nThis CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: url:https://www.ncbi.nlm.nih.gov/books/NBK599589"
},
{
- "id": "pmid:36476347",
+ "id": "genereviews:NBK1126",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/36476347",
- "title": "Spinocerebellar ataxia type 17-digenic TBP/STUB1 disease: neuropathologic features of an autopsied patient.",
- "type": "article-journal",
- "doi": "10.1186/s40478-022-01486-6",
+ "link": "http://www.ncbi.nlm.nih.gov/books/NBK1126/",
+ "title": "Oculopharyngeal Muscular Dystrophy",
+ "type": "chapter",
+ "doi": "",
"authors": [
- ["Rie", "Saito"],
- ["Yui", "Tada"],
- ["Daisuke", "Oikawa"],
- ["Yusuke", "Sato"],
- ["Makiko", "Seto"],
- ["Akira", "Satoh"],
- ["Kodai", "Kume"],
- ["Nozomi", "Ueki"],
- ["Masahiro", "Nakashima"],
- ["Shintaro", "Hayashi"],
- ["Yasuko", "Toyoshima"],
- ["Fuminori", "Tokunaga"],
- ["Hideshi", "Kawakami"],
- ["Akiyoshi", "Kakita"]
+ ["Capucine", "Trollet"],
+ ["Alexis", "Boulinguiez"],
+ ["Fanny", "Roth"],
+ ["Tanya", "Stojkovic"],
+ ["Gillian", "Butler-Browne"],
+ ["Teresinha", "Evangelista"],
+ ["Jean", "Lacau St Guily"],
+ ["Pascale", "Richard"]
],
- "publisher": "Acta neuropathologica communications",
- "issn": "2051-5960",
- "date": "2022-12-07",
- "abstract": "Spinocerebellar ataxia (SCA) type 17-digenic TBP/STUB1 disease (SCA17-DI) has been recently segregated from SCA17, caused by digenic inheritance of two gene mutations - intermediate polyglutamine-encoding CAG/CAA repeat expansions (polyQ) in TBP (TBP",
- "language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36476347"
+ "publisher": "GeneReviews\u00ae",
+ "issn": "",
+ "date": "1993-01-01",
+ "abstract": "Oculopharyngeal muscular dystrophy (OPMD) is characterized by ptosis and dysphagia due to selective involvement of the muscles of the eyelids and pharynx, respectively. For the vast majority of individuals with typical OPMD, the mean age of onset of ptosis is usually 48 years and of dysphagia 50 years; in 5%-10% of individuals with severe OPMD, onset of ptosis and dysphagia occur before age 45 years and is associated with lower limb girdle weakness starting around age 60 years. Swallowing difficulties, which determine prognosis, increase the risk for potentially life-threatening aspiration pneumonia and poor nutrition. Other manifestations as the disease progresses can include limitation of upward gaze, tongue atrophy and weakness, chewing difficulties, wet voice, facial muscle weakness, axial muscle weakness, and proximal limb girdle weakness predominantly in lower limbs. Some individuals with severe involvement will eventually need a wheelchair. Neuropsychological tests have shown altered scores in executive functions in some., The diagnosis of OPMD is established in a proband with a suggestive phenotype in whom either of the following genetic findings are identified: a heterozygous GCN trinucleotide repeat expansion of 11 to 18 repeats in the first exon of PABPN1 (~90% of affected individuals) or biallelic GCN trinucleotide repeat expansions that are either compound heterozygous (GCN[11] with a second expanded allele) or homozygous (GCN[11]+[11], GCN[12]+[12], GCN[13]+[13], etc.) (~10% of affected individuals)., Treatment of manifestations: Treatment for ptosis may include blepharoplasty by either resection of the levator palpebrea aponeurosis or frontal suspension of the eyelids. The initial treatment for dysphagia is dietary modification; surgical intervention for dysphagia should be considered when symptomatic dysphagia has a significant impact on quality of life. Physical and occupational therapy are encouraged; assistive devices may be necessary to prevent falls and assist with walking and mobility. Neuropsychological support as needed. Surveillance: Routine evaluation of: neuromuscular and oculomotor involvement; dysphagia including nutritional status and diet; respiratory function given the increased risk for both aspiration and nocturnal hypoventilation; and cognitive function including development of psychiatric symptoms., OPMD is inherited in an autosomal dominant manner. The risk to sibs of a proband depends on the genetic status of the parents of the proband: If one parent of a proband is heterozygous for a GCN repeat expansion in PABPN1 (GCN[11_18]+ [10]) and the other parent has two normal alleles (GCN[10]+[10]), the risk to the sibs of inheriting a GCN repeat expansion is 50%. If both parents of the proband are heterozygous for a GCN repeat expansion, sibs have a 25% risk of inheriting two GCN repeat expansions and a 50% risk of inheriting one GCN repeat expansion. If one parent of the proband has biallelic GCN repeat expansions and the other parent has two normal alleles, all sibs will inherit a GCN repeat expansion. If one parent of the proband has biallelic GCN repeat expansions and the other parent is heterozygous for a GCN repeat expansion, sibs of the proband have a 50% risk of inheriting biallelic GCN repeat expansions and 50% risk of inheriting one GCN repeat expansion. Sibs who inherit either one or two GCN repeat expansions will be affected.",
+ "language": "eng",
+ "note": "PMID: 20301305\nThis CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: url:https://www.ncbi.nlm.nih.gov/books/NBK1126"
},
{
- "id": "pmid:36422518",
+ "id": "genereviews:NBK1427",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/36422518",
- "title": "Intermediate repeat expansions of TBP and STUB1: Genetic modifier or pure digenic inheritance in spinocerebellar ataxias?",
- "type": "article-journal",
- "doi": "10.1016/j.gim.2022.10.009",
+ "link": "http://www.ncbi.nlm.nih.gov/books/NBK1427/",
+ "title": "Congenital Central Hypoventilation Syndrome",
+ "type": "chapter",
+ "doi": "",
"authors": [
- ["Mathieu", "Barbier"],
- ["Claire-Sophie", "Davoine"],
- ["Emilien", "Petit"],
- ["Maximilien", "Porch\u00e9"],
- ["L\u00e9na", "Guillot-Noel"],
- ["Sabrina", "Sayah"],
- ["Anne-Laure", "Fauret"],
- ["Jean-Philippe", "Neau"],
- ["Lucie", "Guyant-Mar\u00e9chal"],
- ["Didier", "Deffond"],
- ["Christine", "Tranchant"],
- ["Cyril", "Goizet"],
- ["Giulia", "Coarelli"],
- ["Anna", "Castrioto"],
- ["Stephan", "Klebe"],
- ["Claire", "Ewenczyk"],
- ["Anna", "Heinzmann"],
- ["Perrine", "Charles"],
- ["Maya", "Tchikviladz\u00e9"],
- ["Christine", "Van Broeckhoven"],
- ["Alexis", "Brice"],
- ["Alexandra", "Durr"]
+ ["Debra E.", "Weese-Mayer"],
+ ["Casey M.", "Rand"],
+ ["Ilya", "Khaytin"],
+ ["Susan M.", "Slattery"],
+ ["Kai Lee", "Yap"],
+ ["Mary L.", "Marazita"],
+ ["Elizabeth M.", "Berry-Kravis"]
],
- "publisher": "Genetics in medicine : official journal of the American College of Medical Genetics",
- "issn": "1530-0366",
- "date": "2022-11-23",
- "abstract": "CAG/CAA repeat expansions in TBP",
- "language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36422518"
+ "publisher": "GeneReviews\u00ae",
+ "issn": "",
+ "date": "1993-01-01",
+ "abstract": "Congenital central hypoventilation syndrome (CCHS) represents the extreme manifestation of autonomic nervous system dysregulation (ANSD) with the hallmark of disordered respiratory control. The age of initial recognition of CCHS ranges from neonatal onset (i.e., in the first 30 days of life) to (less commonly) later onset (from 1 month to adulthood). Neonatal-onset CCHS is characterized by apparent hypoventilation with monotonous respiratory rates and shallow breathing either during sleep only or while awake as well as asleep; ANSD including decreased heart rate beat-to-beat variability and sinus pauses; altered temperature regulation; and altered pupillary response to light. Some children have altered development of neural crest-derived structures (i.e., Hirschsprung disease, altered esophageal motility/dysphagia, and severe constipation even in the absence of Hirschsprung disease) and/or tumors of neural crest origin (neuroblastoma, ganglioneuroma, and ganglioneuroblastoma). Neurocognitive delay is variable, and possibly influenced by cyanotic breath holding, prolonged sinus pauses, need for 24-hour/day artificial ventilation, and seizures. Later-onset CCHS is characterized by alveolar hypoventilation during sleep and attenuated manifestations of ANSD., The diagnosis of CCHS is established in a proband with suggestive findings and a heterozygous PHOX2B pathogenic variant identified on molecular genetic testing., Treatment of manifestations: Management by multidisciplinary specialists, including pediatric pulmonology, sleep medicine, cardiology, oncology, ophthalmology, gastroenterology, neurodevelopmental psychology, and neurology, is recommended. The treatment goals for CCHS are to secure the airway and to use chronic artificial ventilatory support at home to compensate for the hypoventilation and the altered/absent ventilatory responses to hypoxemia and hypercarbia. Prolonged transient asystoles that may present as syncope and/or staring spells and are of significant duration (\u22653.0 seconds) may warrant placement of a cardiac pacemaker; abnormal pupillary reactivity may necessitate protective eye wear given the amount of light exposure in daily life from LED lights, and screen time in educational settings, computer-based work environments, and mobile devices. Other findings treated as per standard practice include Hirschsprung disease and other gastrointestinal motility issues; tumors of neural crest origin; and cognitive impairment/delay. Surveillance: Assess every six months for the first three years, then annually thereafter: (1) in a pediatric respiratory physiology laboratory spontaneous breathing awake (in varied age-appropriate activities of daily living during the daytime and before sleep) and asleep, with recording of respiratory inductance plethysmography of the chest and abdomen, hemoglobin saturation with pulse waveform, end-tidal carbon dioxide level with visible waveform, electrocardiogram, blood pressure, cerebral regional blood flow/oxygenation, and appropriate sleep state staging measures; (2) hemoglobin/hematocrit and reticulocyte count for polycythemia; (3) 72-hour Holter recording for abrupt, prolonged asystoles; (4) echocardiogram changes consistent with right ventricular hypertrophy and cor pulmonale; (5) neurocognitive assessment/educational needs; and (6) comprehensive age-appropriate noninvasive autonomic testing. Agents/circumstances to avoid: Swimming and breath-holding contests (risk of asphyxia, death); alcohol (respiratory depression), recreational drugs (varied effects including death), and prescription as well as non-prescription medications/sedatives/anesthetics that could induce respiratory depression. Evaluation of relatives at risk: It is appropriate to clarify the genetic status of parents, sibs, and offspring of an individual with CCHS in order to identify as early as possible family members who would benefit from prompt initiation of treatment, surveillance, and awareness of agents/circumstances to avoid., CCHS is typically inherited in an autosomal dominant manner (CCHS caused by biallelic reduced penetrance PHOX2B pathogenic variants has been reported in two families). The majority of affected individuals have the disorder as the result of a de novo pathogenic variant. Somatic/germline mosaicism is present in 5%-25% of asymptomatic parents. If a parent of the proband is known to be heterozygous for the PHOX2B pathogenic variant identified in the proband, the risk to the sibs of inheriting the pathogenic variant is 50%. Once the PHOX2B pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible (because of the high frequency of parental mosaicism in CCHS, a fetus should be considered at risk for CCHS even if the PHOX2B pathogenic variant detected in the proband was not identified in either parent).",
+ "language": "eng",
+ "note": "PMID: 20301600\nThis CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: url:https://www.ncbi.nlm.nih.gov/books/NBK1427"
},
{
- "id": "pmid:35482253",
+ "id": "genereviews:NBK1513",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/35482253",
- "title": "Calpains as novel players in the molecular pathogenesis of spinocerebellar ataxia type 17.",
- "type": "article-journal",
- "doi": "10.1007/s00018-022-04274-6",
+ "link": "http://www.ncbi.nlm.nih.gov/books/NBK1513/",
+ "title": "Cleidocranial Dysplasia Spectrum Disorder",
+ "type": "chapter",
+ "doi": "",
"authors": [
- ["Jonasz Jeremiasz", "Weber"],
- ["Stefanie Cari", "Anger"],
- ["Priscila", "Pereira Sena"],
- ["Rana Dilara", "Incebacak Eltemur"],
- ["Chrisovalantou", "Huridou"],
- ["Florian", "Fath"],
- ["Caspar", "Gross"],
- ["Nicolas", "Casadei"],
- ["Olaf", "Riess"],
- ["Huu Phuc", "Nguyen"]
+ ["Keren", "Machol"],
+ ["Roberto", "Mendoza-Londono"],
+ ["Brendan", "Lee"]
+ ],
+ "publisher": "GeneReviews\u00ae",
+ "issn": "",
+ "date": "1993-01-01",
+ "abstract": "Cleidocranial dysplasia (CCD) spectrum disorder is a skeletal dysplasia that represents a clinical continuum ranging from classic CCD (triad of delayed closure of the cranial sutures, hypoplastic or aplastic clavicles, and dental abnormalities), to mild CCD, to isolated dental anomalies without other skeletal features. Individuals with classic CCD spectrum disorder typically have abnormally large, wide-open fontanelles at birth that may remain open throughout life. Clavicular hypoplasia can result in narrow, sloping shoulders that can be opposed at the midline. Moderate short stature may be observed, with most affected individuals being shorter than their unaffected sibs. Dental anomalies may include delayed eruption of secondary dentition, failure to shed the primary teeth, and supernumerary teeth. Individuals with CCD spectrum disorder are at increased risk of developing recurrent sinus infections, recurrent ear infections leading to conductive hearing loss, and upper airway obstruction. Intelligence is typically normal., The diagnosis of CCD spectrum disorder is established in an individual with typical clinical and radiographic findings and/or a heterozygous pathogenic variant in RUNX2 identified by molecular genetic testing., Treatment of manifestations: If the cranial vault defect is significant, the head needs protection from blunt trauma; helmets may be used for high-risk activities. Surgical cosmesis for depressed forehead or lengthening of hypoplastic clavicles can be considered. Careful planning of anesthetic management due to craniofacial and dental abnormalities. Consultation with an otolaryngologist to assist in securing the airway. Consideration of alternative anesthetic approaches, including neuraxial block, taking into account possible spine abnormalities. If bone density is below normal, treatment with calcium and vitamin D supplementation. Dental procedures to address retention of primary dentition, presence of supernumerary teeth, and non-eruption of secondary dentition. Such procedures may include prosthetic replacements, removal of the supernumerary teeth followed by surgical repositioning of the secondary teeth, and a combination of surgical and orthodontic measures for actively erupting and aligning the impacted secondary teeth. Speech therapy as needed. Aggressive treatment of sinus and middle ear infections; consideration of tympanostomy tubes for recurrent middle ear infections; regular immunizations including influenza. Sleep study in those with manifestations of obstructive sleep apnea; surgical intervention may be required for upper airway obstruction. Surveillance: Monitor children for orthopedic complications, dental abnormalities, sinus and ear infections, upper airway obstruction, hearing loss, and speech issues. DXA scan to assess bone mineral density beginning in early adolescence and every five to ten years thereafter. Agents/circumstances to avoid: Helmets and protective devices should be worn when participating in high-risk activities. Pregnancy management: Monitor affected women during pregnancy for cephalopelvic disproportion., CCD spectrum disorder is inherited in an autosomal dominant manner. The proportion of individuals with CCD spectrum disorder caused by a de novo pathogenic variant is high. Each child of an individual with CCD spectrum disorder has a 50% chance of inheriting the RUNX2 pathogenic variant. Once the RUNX2 pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing for CCD spectrum disorder are possible.",
+ "language": "eng",
+ "note": "PMID: 20301686\nThis CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: url:https://www.ncbi.nlm.nih.gov/books/NBK1513"
+},
+{
+ "id": "genereviews:NBK1530",
+ "manubot_success": true,
+ "link": "http://www.ncbi.nlm.nih.gov/books/NBK1530/",
+ "title": "Holoprosencephaly Overview",
+ "type": "chapter",
+ "doi": "",
+ "authors": [
+ ["Cedrik", "Tekendo-Ngongang"],
+ ["Maximilian", "Muenke"],
+ ["Paul", "Kruszka"]
],
- "publisher": "Cellular and molecular life sciences : CMLS",
- "issn": "1420-9071",
- "date": "2022-04-28",
- "abstract": "Spinocerebellar ataxia type 17 (SCA17) is a neurodegenerative disease caused by a polyglutamine-encoding trinucleotide repeat expansion in the gene of transcription factor TATA box-binding protein (TBP). While its underlying pathomechanism is elusive, polyglutamine-expanded TBP fragments of unknown origin mediate the mutant protein's toxicity. Calcium-dependent calpain proteases are protagonists in neurodegenerative disorders. Here, we demonstrate that calpains cleave TBP, and emerging C-terminal fragments mislocalize to the cytoplasm. SCA17 cell and rat models exhibited calpain overactivation, leading to excessive fragmentation and depletion of neuronal proteins in vivo. Transcriptome analysis of SCA17 cells revealed synaptogenesis and calcium signaling perturbations, indicating the potential cause of elevated calpain activity. Pharmacological or genetic calpain inhibition reduced TBP cleavage and aggregation, consequently improving cell viability. Our work underlines the general significance of calpains and their activating pathways in neurodegenerative disorders and presents these proteases as novel players in the molecular pathogenesis of SCA17.",
- "language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35482253"
+ "publisher": "GeneReviews\u00ae",
+ "issn": "",
+ "date": "1993-01-01",
+ "abstract": "The purpose of this overview is to: 1.. Describe the clinical characteristics of holoprosencephaly; 2.. Review the genetic causes of holoprosencephaly; 3.. Provide an evaluation strategy to identify (when possible) the genetic cause of holoprosencephaly in a proband; 4.. Inform genetic counseling of family members of an individual with holoprosencephaly.",
+ "language": "eng",
+ "note": "PMID: 20301702\nThis CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: url:https://www.ncbi.nlm.nih.gov/books/NBK1530"
},
{
- "id": "pmid:34906452",
+ "id": "pmid:19760265",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/34906452",
- "title": "Digenic inheritance of STUB1 variants and TBP polyglutamine expansions explains the incomplete penetrance of SCA17 and SCA48.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19760265",
+ "title": "Mutations in the VNTR of the carboxyl-ester lipase gene (CEL) are a rare cause of monogenic diabetes.",
"type": "article-journal",
- "doi": "10.1016/j.gim.2021.08.003",
+ "doi": "10.1007/s00439-009-0740-8",
"authors": [
- ["Stefania", "Magri"],
- ["Lorenzo", "Nanetti"],
- ["Cinzia", "Gellera"],
- ["Elisa", "Sarto"],
- ["Elena", "Rizzo"],
- ["Alessia", "Mongelli"],
- ["Benedetta", "Ricci"],
- ["Roberto", "Fancellu"],
- ["Luisa", "Sambati"],
- ["Pietro", "Cortelli"],
- ["Alfredo", "Brusco"],
- ["Maria Grazia", "Bruzzone"],
- ["Caterina", "Mariotti"],
- ["Daniela", "Di Bella"],
- ["Franco", "Taroni"]
+ ["Janniche", "Torsvik"],
+ ["Stefan", "Johansson"],
+ ["Anders", "Johansen"],
+ ["Jakob", "Ek"],
+ ["Jayne", "Minton"],
+ ["Helge", "Raeder"],
+ ["Sian", "Ellard"],
+ ["Andrew", "Hattersley"],
+ ["Oluf", "Pedersen"],
+ ["Torben", "Hansen"],
+ ["Anders", "Molven"],
+ ["P\u00e5l R", "Nj\u00f8lstad"]
],
- "publisher": "Genetics in medicine : official journal of the American College of Medical Genetics",
- "issn": "1530-0366",
- "date": "2021-11-30",
- "abstract": "This study aimed to unravel the genetic factors underlying missing heritability in spinocerebellar ataxia type 17 (SCA17) caused by polyglutamine-encoding CAG/CAA repeat expansions in the TBP gene. Alleles with >49 CAG/CAA repeats are fully penetrant. Most patients, however, carry intermediate TBP",
+ "publisher": "Human genetics",
+ "issn": "1432-1203",
+ "date": "2009-09-17",
+ "abstract": "We have previously shown that heterozygous single-base deletions in the carboxyl-ester lipase (CEL) gene cause exocrine and endocrine pancreatic dysfunction in two multigenerational families. These deletions were found in the first and fourth repeats of a variable number of tandem repeats (VNTR), which has proven challenging to sequence due to high GC-content and considerable length variation. We have therefore developed a screening method consisting of a multiplex PCR followed by fragment analysis. The method detected putative disease-causing insertions and deletions in the proximal repeats of the VNTR, and determined the VNTR-length of each allele. When blindly testing 56 members of the two families with known single-base deletions in the CEL VNTR, the method correctly assessed the mutation carriers. Screening of 241 probands from suspected maturity-onset diabetes of the young (MODY) families negative for mutations in known MODY genes (95 individuals from Denmark and 146 individuals from UK) revealed no deletions in the proximal repeats of the CEL VNTR. However, we found one Danish patient with a short, novel CEL allele containing only three VNTR repeats (normal range 7-23 in healthy controls). This allele co-segregated with diabetes or impaired glucose tolerance in the patient's family as six of seven mutation carriers were affected. We also identified individuals who had three copies of a complete CEL VNTR. In conclusion, the CEL gene is highly polymorphic, but mutations in CEL are likely to be a rare cause of monogenic diabetes.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34906452"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19760265"
},
{
- "id": "pmid:31919387",
+ "id": "pmid:16369531",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/31919387",
- "title": "Interferon mediated neuroinflammation in polyglutamine disease is not caused by RNA toxicity.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/16369531",
+ "title": "Mutations in the CEL VNTR cause a syndrome of diabetes and pancreatic exocrine dysfunction.",
"type": "article-journal",
- "doi": "10.1038/s41419-019-2193-x",
+ "doi": "10.1038/ng1708",
"authors": [
- ["Aksheev", "Bhambri"],
- ["Akeeth", "Pinto"],
- ["Beena", "Pillai"]
+ ["Helge", "Raeder"],
+ ["Stefan", "Johansson"],
+ ["P\u00e5l I", "Holm"],
+ ["Ingfrid S", "Haldorsen"],
+ ["Eric", "Mas"],
+ ["V\u00e9ronique", "Sbarra"],
+ ["Ingrid", "Nermoen"],
+ ["Stig A", "Eide"],
+ ["Louise", "Grevle"],
+ ["Lise", "Bj\u00f8rkhaug"],
+ ["J\u00f8rn V", "Sagen"],
+ ["Lage", "Aksnes"],
+ ["Oddmund", "S\u00f8vik"],
+ ["Dominique", "Lombardo"],
+ ["Anders", "Molven"],
+ ["P\u00e5l Rasmus", "Nj\u00f8lstad"]
],
- "publisher": "Cell death & disease",
- "issn": "2041-4889",
- "date": "2020-01-02",
- "abstract": "Polyglutamine diseases are neurodegenerative diseases that occur due to the expansion of CAG repeat regions in coding sequences of genes. Previously, we have shown the formation of large protein aggregates along with activation of the interferon pathway leading to apoptosis in a cellular model of SCA17. Here, we corroborate our previous results in a tetracycline-inducible model of SCA17. Interferon gamma and lambda were upregulated in 59Q-TBP expressing cells as compared to 16Q-TBP expressing cells. Besides interferon-stimulated genes, the SCA17 model and Huntington's mice brain samples showed upregulation of RNA sensors. However, in this improved model interferon pathway activation and apoptosis preceded the formation of large polyglutamine aggregates, suggesting a role for CAG repeat RNA or soluble protein aggregates. A polyglutamine minus mutant of TBP, expressing polyCAG mRNA, was created by site directed mutagenesis of 10 potential start codons. Neither this long CAG embedded mRNA nor short polyCAG RNA could induce interferon pathway genes or cause apoptosis. polyQ-TBP induced the expression of canonical RNA sensors but the downstream transcription factor, IRF3, showed a muted response. We found that expanded CAG repeat RNA is not sufficient to account for the neuronal apoptosis. Neuronal cells sense expanded CAG repeats embedded in messenger RNAs of protein-coding genes. However, polyglutamine containing protein is responsible for the interferon-mediated neuroinflammation and cell death seen in polyglutamine disease. Thus, we delineate the inflammatory role of CAG repeats in the mRNA from the resulting polyglutamine tract in the protein. Embedded in messenger RNAs of protein-coding regions, the cell senses CAG repeat expansion and induces the expression of RNA sensors and interferon-stimulated genes.",
+ "publisher": "Nature genetics",
+ "issn": "1061-4036",
+ "date": "2005-12-20",
+ "abstract": "Dysfunction of the exocrine pancreas is observed in diabetes, but links between concurrent exocrine and endocrine pancreatic disease and contributing genetic factors are poorly characterized. We studied two families with diabetes and exocrine pancreatic dysfunction by genetic, physiological and in vitro functional studies. A genome-wide screen in Family 1 linked diabetes to chromosome 9q34 (maximal lod score 5.07). Using fecal elastase deficiency as a marker of exocrine pancreatic dysfunction refined the critical chromosomal region to 1.16 Mb (maximal lod score 11.6). Here, we identified a single-base deletion in the variable number of tandem repeats (VNTR)-containing exon 11 of the carboxyl ester lipase (CEL) gene, a major component of pancreatic juice and responsible for the duodenal hydrolysis of cholesterol esters. Screening subjects with maturity-onset diabetes of the young identified Family 2, with another single-base deletion in CEL and a similar phenotype with beta-cell failure and pancreatic exocrine disease. The in vitro catalytic activities of wild-type and mutant CEL protein were comparable. The mutant enzyme was, however, less stable and secreted at a lower rate. Furthermore, we found some evidence for an association between common insertions in the CEL VNTR and exocrine dysfunction in a group of 182 unrelated subjects with diabetes (odds ratio 4.2 (1.6, 11.5)). Our findings link diabetes to the disrupted function of a lipase in the pancreatic acinar cells.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31919387"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16369531"
},
{
- "id": "pmid:30532692",
+ "id": "pmid:40641008",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/30532692",
- "title": "Complexity of the Genetics and Clinical Presentation of Spinocerebellar Ataxia 17.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/40641008",
+ "title": "Characterizing Cellular Expansion of Idecabtagene Vicleucel and Association with Clinical Efficacy and Safety in Patients with Triple-Class-Exposed Relapsed/Refractory Multiple Myeloma.",
"type": "article-journal",
- "doi": "10.3389/fncel.2018.00429",
+ "doi": "10.1002/jcph.70075",
"authors": [
- ["Suran", "Nethisinghe"],
- ["Wei N", "Lim"],
- ["Heather", "Ging"],
- ["Anna", "Zeitlberger"],
- ["Rosella", "Abeti"],
- ["Sally", "Pemble"],
- ["Mary G", "Sweeney"],
- ["Robyn", "Labrum"],
- ["Charisse", "Cervera"],
- ["Henry", "Houlden"],
- ["Elisabeth", "Rosser"],
- ["Patricia", "Limousin"],
- ["Angus", "Kennedy"],
- ["Michael P", "Lunn"],
- ["Kailash P", "Bhatia"],
- ["Nicholas W", "Wood"],
- ["John", "Hardy"],
- ["James M", "Polke"],
- ["Liana", "Veneziano"],
- ["Alfredo", "Brusco"],
- ["Mary B", "Davis"],
- ["Paola", "Giunti"]
+ ["Fan", "Wu"],
+ ["Xirong", "Zheng"],
+ ["Joseph", "Burnett"],
+ ["Madhan", "Masilamani"],
+ ["Wanying", "Zhang"],
+ ["Xiaobo", "Zhong"],
+ ["Andrea", "Caia"],
+ ["Mark", "Cook"],
+ ["Julia", "Piasecki"],
+ ["Anna", "Kondic"],
+ ["Manisha", "Lamba"],
+ ["Jian", "Zhou"]
],
- "publisher": "Frontiers in cellular neuroscience",
- "issn": "1662-5102",
- "date": "2018-11-23",
- "abstract": "Spinocerebellar ataxia type 17 (SCA17) is a rare autosomal dominant neurodegenerative disease caused by a CAG repeat expansion in the TATA-box binding protein gene (",
+ "publisher": "Journal of clinical pharmacology",
+ "issn": "1552-4604",
+ "date": "2025-07-10",
+ "abstract": "Idecabtagene vicleucel (ide-cel, ABECMA) is an autologous, B-cell maturation antigen-directed, chimeric antigen receptor (CAR) T-cell therapy, which has demonstrated significantly improved progression-free survival (PFS) and overall response rate (ORR) in patients with triple-class-exposed relapsed/refractory multiple myeloma (TCE RRMM). Here, we characterize cellular expansion of ide-cel in vivo and further evaluate associations between cellular expansion and clinical efficacy and safety endpoints. The exposure parameters of ide-cel were evaluated through non-compartmental analysis methods using the time course data of CAR transgene copy numbers collected from the ide-cel arm of Study KarMMa-3 (NCT03651128). Multivariable regression analyses were conducted between the exposure parameters and clinical responses to characterize relationships between cellular expansion in vivo and clinical outcomes and to evaluate potential effects of covariates on the exposure-response (E-R) relationships. There appears to be lack of a strong association between actual ide-cel dose and cellular expansion at the dose range evaluated in Study KarMMa-3. The multivariable E-R regression models suggest positive relationships between cellular expansion and clinical efficacy and safety endpoints, with higher exposure associated with longer PFS, higher ORR, and higher rates of cytokine release syndrome requiring tocilizumab or corticosteroids. The current analyses do not identify any clinically relevant covariate effects on the E-R relationships. The positive exposure-response relationships were found to be overall similar between KarMMa-3 and a previous study KarMMa. The modeling analyses, paired with clinical data, support extending the dose range from previously approved 300-460 \u00d7 10",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40641008"
+},
+{
+ "id": "pmid:39710966",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/39710966",
+ "title": "Brexucabtagene autoleucel in-vivo expansion and BTKi refractoriness have a negative influence on progression-free survival in mantle cell lymphoma: Results from CART-SIE study.",
+ "type": "article-journal",
+ "doi": "10.1111/bjh.19961",
+ "authors": [
+ ["Federico", "Stella"],
+ ["Annalisa", "Chiappella"],
+ ["Martina", "Magni"],
+ ["Francesca", "Bonifazi"],
+ ["Chiara", "De Philippis"],
+ ["Maurizio", "Musso"],
+ ["Ilaria", "Cutini"],
+ ["Silva", "Ljevar"],
+ ["Anna Maria", "Barbui"],
+ ["Mirko", "Farina"],
+ ["Massimo", "Martino"],
+ ["Massimo", "Massaia"],
+ ["Giovanni", "Grillo"],
+ ["Piera", "Angelillo"],
+ ["Barbara", "Botto"],
+ ["Francesca", "Patriarca"],
+ ["Mauro", "Krampera"],
+ ["Luca", "Arcaini"],
+ ["Maria Chiara", "Tisi"],
+ ["Pierluigi", "Zinzani"],
+ ["Federica", "Sor\u00e0"],
+ ["Stefania", "Bramanti"],
+ ["Martina", "Pennisi"],
+ ["Cristiana", "Carniti"],
+ ["Paolo", "Corradini"]
+ ],
+ "publisher": "British journal of haematology",
+ "issn": "1365-2141",
+ "date": "2024-12-22",
+ "abstract": "Brexucabtagene autoleucel (brexu-cel) has revolutionized the treatment of patients affected by mantle cell lymphomas. In this prospective, observational multicentre study, we evaluated 106 patients, with longitudinal brexu-cel kinetics in peripheral blood monitored in 61 of them. Clinical outcomes and toxicities are consistent with previous real-world evidence studies. Notably, beyond established poor prognostic factors-such as blastoid variant and elevated lactate dehydrogenase-Bruton tyrosine-kinase inhibitors (BTKi) refractoriness and platelet count emerged as significant predictors of survival. Specifically, the 1-year overall survival was 56% in BTKi-refractory patients compared to 92% in BTKi-relapsed patients (p\u2009=\u20090.0001). Our study also demonstrated that in-vivo monitoring of brexu-cel expansion is feasible and correlates with progression-free survival and toxicities. Progression-free survival at 1\u2009year was 74% in patients categorized as strong expanders, based on brexu-cel peak concentration, versus 54% in poor expanders (p\u2009=\u20090.02). Furthermore, in-vivo expansion helped identify a high-risk group of non-responders, those with progressive or stable disease at the 90-day post-infusion evaluation (OR\u2009=\u20094.7, 95% CI\u2009=\u20091.1-34, p\u2009=\u20090.04) characterized by dismal outcomes. When integrated with other clinical factors, monitoring brexu-cel expansion could assist in recognizing patients at high risk of early relapse.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30532692"
-},
-{
- "id": "pmid:28821675",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/28821675",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:28821675']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39710966"
},
{
- "id": "pmid:27865706",
+ "id": "pmid:38483348",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/27865706",
- "title": "Age-related length variability of polymorphic CAG repeats.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38483348",
+ "title": "Common single-base insertions in the VNTR of the carboxyl ester lipase (CEL) gene are benign and also likely to arise somatically in the exocrine pancreas.",
"type": "article-journal",
- "doi": "10.1016/j.dnarep.2016.10.003",
+ "doi": "10.1093/hmg/ddae034",
"authors": [
- ["Monica", "Sanchez-Contreras"],
- ["Fernando", "Cardozo-Pelaez"]
+ ["Ranveig S", "Brekke"],
+ ["Anny", "Gravdal"],
+ ["Khadija", "El Jellas"],
+ ["Grace E", "Curry"],
+ ["Jianguo", "Lin"],
+ ["Steven J", "Wilhelm"],
+ ["Solrun J", "Steine"],
+ ["Eric", "Mas"],
+ ["Stefan", "Johansson"],
+ ["Mark E", "Lowe"],
+ ["Bente B", "Johansson"],
+ ["Xunjun", "Xiao"],
+ ["Karianne", "Fjeld"],
+ ["Anders", "Molven"]
],
- "publisher": "DNA repair",
- "issn": "1568-7856",
- "date": "2016-10-15",
- "abstract": "Somatic instability of CAG repeats has been associated with the clinical progression of CAG repeat diseases. Aging and DNA repair processes influence the somatic stability of CAG repeat in disease and in mouse models. However, most of the studies have focused on genetically engineered transgenic repeats and little is known about the stability of naturally polymorphic CAG repeats. To study whether age and/or DNA repair activity have an effect on the somatic stability of CAG repeats, we analyzed variations of the length of naturally polymorphic CAG repeats in the striatum of young and aged WT and ogg1 KO mice. Some multiple and long polymorphic CAG repeats were observed to have variable length in the striatum of aged mice. Interestingly, a low level of repeat variability was detected in the CAG repeat located in tbp, the only mouse polymorphic CAG repeat that is associated with a trinucleotide disease in humans, in the striatum of aged mice and not in young mice. We propose that age may have an effect on the somatic stability of polymorphic CAG repeats and that such an effect depends on intrinsic CAG repeat characteristics.",
+ "publisher": "Human molecular genetics",
+ "issn": "1460-2083",
+ "date": "2024-05-18",
+ "abstract": "The CEL gene encodes carboxyl ester lipase, a pancreatic digestive enzyme. CEL is extremely polymorphic due to a variable number tandem repeat (VNTR) located in the last exon. Single-base deletions within this VNTR cause the inherited disorder MODY8, whereas little is known about VNTR single-base insertions in pancreatic disease. We therefore mapped CEL insertion variants (CEL-INS) in 200 Norwegian patients with pancreatic neoplastic disorders. Twenty-eight samples (14.0%) carried CEL-INS alleles. Most common were insertions in repeat 9 (9.5%), which always associated with a VNTR length of 13 repeats. The combined INS allele frequency (0.078) was similar to that observed in a control material of 416 subjects (0.075). We performed functional testing in HEK293T cells of a set of CEL-INS variants, in which the insertion site varied from the first to the 12th VNTR repeat. Lipase activity showed little difference among the variants. However, CEL-INS variants with insertions occurring in the most proximal repeats led to protein aggregation and endoplasmic reticulum stress, which upregulated the unfolded protein response. Moreover, by using a CEL-INS-specific antibody, we observed patchy signals in pancreatic tissue from humans without any CEL-INS variant in the germline. Similar pancreatic staining was seen in knock-in mice expressing the most common human CEL VNTR with 16 repeats. CEL-INS proteins may therefore be constantly produced from somatic events in the normal pancreatic parenchyma. This observation along with the high population frequency of CEL-INS alleles strongly suggests that these variants are benign, with a possible exception for insertions in VNTR repeats 1-4.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27865706"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38483348"
},
{
- "id": "pmid:27172828",
+ "id": "pmid:38473919",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/27172828",
- "title": "Trinucleotide repeat expansion of TATA-binding protein gene associated with Parkinson's disease: A Thai multicenter study.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38473919",
+ "title": "Unlocking Predictive Power: Quantitative Assessment of CAR-T Expansion with Digital Droplet Polymerase Chain Reaction (ddPCR).",
"type": "article-journal",
- "doi": "10.1016/j.parkreldis.2016.05.008",
+ "doi": "10.3390/ijms25052673",
"authors": [
- ["Lulin", "Choubtum"],
- ["Pirada", "Witoonpanich"],
- ["Kongkiat", "Kulkantrakorn"],
- ["Suchat", "Hanchaiphiboolkul"],
- ["Sunsanee", "Pongpakdee"],
- ["Somsak", "Tiamkao"],
- ["Teeratorn", "Pulkes"]
+ ["Eugenio", "Galli"],
+ ["Marcello", "Viscovo"],
+ ["Federica", "Fosso"],
+ ["Ilaria", "Pansini"],
+ ["Giacomo", "Di Cesare"],
+ ["Camilla", "Iacovelli"],
+ ["Elena", "Maiolo"],
+ ["Federica", "Sor\u00e0"],
+ ["Stefan", "Hohaus"],
+ ["Simona", "Sica"],
+ ["Silvia", "Bellesi"],
+ ["Patrizia", "Chiusolo"]
],
- "publisher": "Parkinsonism & related disorders",
- "issn": "1873-5126",
- "date": "2016-05-04",
- "abstract": "Spinocerebellar ataxia type 17 (SCA17) is an inherited cerebellar degeneration associated with trinucleotide repeat expansions in the TATA-binding protein gene (TBP). Low-range expansions of TBP have recently been described in association with Parkinson's disease (PD). However, these low-range expansion alleles were also observed in healthy individuals. Prior distinct findings may result from reduced penetrance or age-dependent susceptibility, which may influence phenotypic expression.",
+ "publisher": "International journal of molecular sciences",
+ "issn": "1422-0067",
+ "date": "2024-02-26",
+ "abstract": "Flow cytometry (FCM) and quantitative PCR (qPCR) are conventional methods for assessing CAR-T expansion, while digital droplet PCR (ddPCR) is emerging as a promising alternative. We monitored CAR-T transcript expansion in 40 B-NHL patients post-infusion of CAR-T products (axi-cel; tisa-cel; and brexu-cel) with both His-Tag FCM and ddPCR techniques. Sensitivity and predictive capacity for efficacy and safety outcomes of ddPCR were analyzed and compared with FCM. A significant correlation between CAR-T counts determined by FCM and CAR transcripts assessed by ddPCR (",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27172828"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38473919"
},
{
- "id": "pmid:26476771",
+ "id": "pmid:38458477",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26476771",
- "title": "Pathological repeat variation at the SCA17/TBP gene in south Indian patients.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38458477",
+ "title": "Early Chimeric Antigen Receptor T Cell Expansion Is Associated with Prolonged Progression-Free Survival for Patients with Relapsed/Refractory Multiple Myeloma Treated with Ide-Cel: A Retrospective Monocentric Study.",
"type": "article-journal",
- "doi": "10.1016/j.jns.2015.07.044",
+ "doi": "10.1016/j.jtct.2024.03.003",
"authors": [
- ["Waseem Gul", "Lone"],
- ["Imran Ali", "Khan"],
- ["Noor Ahmad", "Shaik"],
- ["Angmuthu Kanikannan", "Meena"],
- ["Kaipa Prabhakar", "Rao"],
- ["Qurratulain", "Hasan"]
+ ["Leo", "Caillot"],
+ ["Emmanuel", "Sleiman"],
+ ["Ingrid", "Lafon"],
+ ["Marie-Lorraine", "Chretien"],
+ ["Pauline", "Gueneau"],
+ ["Alexandre", "Payssot"],
+ ["Romain", "Pedri"],
+ ["Daniela", "Lakomy"],
+ ["Fran\u00e7ois", "Bailly"],
+ ["Julien", "Guy"],
+ ["Jean-Pierre", "Quenot"],
+ ["Herve", "Avet-Loiseau"],
+ ["Denis", "Caillot"]
],
- "publisher": "Journal of the neurological sciences",
- "issn": "1878-5883",
- "date": "2015-08-21",
- "abstract": "Despite the intense debate around the repeat instability reported on the large group of neurological disorders caused by trinucleotide repeat expansions, little is known about the mutation process underlying alleles in the normal range, diseases range, large normal alleles (LNAs). In this study, we assessed the CAG repeats at SCA17 in 188 clinical SCA patients and 100 individuals without any neurological signs. This highly polymorphic population displayed high variability in the CAG repeats and ranged from 19-38 CAG repeats in patients with mode of 20 and 19-32 CAG repeats in controls with mode of 24. The triplet repeat expansion was not detected in any of the 188 patients, as per the reference pathogenic range (>43 repeats); however, 2.7% of the patients had >33 CAG repeats with a clinical phenotype close to what is expected of SCA 17 patients. The findings of this study implicate a more sophisticated interpretation of SCA17 gene and raise the question about the diagnostic thresh hold between normal and expanded repeats in our population.",
+ "publisher": "Transplantation and cellular therapy",
+ "issn": "2666-6367",
+ "date": "2024-03-07",
+ "abstract": "The outcomes of patients with relapsed and refractory multiple myeloma (RRMM) previously treated with the 3 main classes of myeloma therapy-immunomodulatory drugs, proteasome inhibitors, and anti-CD38 antibodies-remain poor. Recently, based on the phase II pivotal KarMMa trial showing prolonged overall survival (OS) and progression-free survival (PFS) in heavily treated patients, idecabtagene vicleucel (ide-cel), a B cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell therapy (CAR-T) product, was approved in the United States for the treatment of RRMM. In France, since June 2021, an early access program has authorized the use of ide-cel in the setting of RRMM (defined as progressive myeloma after at least 3 previous regimens, including the 3 main antimyeloma therapies). We report the first French experience through this early access program in a retrospective study of 24 consecutive patients treated with ide-cel at our institution. The patients were evaluated according to International Myeloma Working Group criteria and by positron emission tomography computed tomography (PET-CT) at 1, 3, 6, 9, and 12 months after ide-cel infusion. Most patients had adverse cytogenetic abnormalities, and RRMM with triple-refractory drugs were seen in 79%. Bridging therapy was required for 19 of 24 patients. Before CAR-T cell infusion, lymphodepletion with fludarabine and cyclophosphamide was systematically performed. The median follow-up was 15.2 months. At 3 months after ide-cel infusion, 92% of patients achieved at least a partial response, and 50% achieved a complete response or better (\u2265CR). At 6 months, 70% of patients had a persistent \u2265CR. At 3 and 6 months, bone marrow minimal residual disease (10",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26476771"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38458477"
},
{
- "id": "pmid:26387956",
+ "id": "pmid:36379850",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26387956",
- "title": "Large Polyglutamine Repeats Cause Muscle Degeneration in SCA17 Mice.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/36379850",
+ "title": "The genetic risk factor CEL-HYB1 causes proteotoxicity and chronic pancreatitis in mice.",
"type": "article-journal",
- "doi": "10.1016/j.celrep.2015.08.060",
+ "doi": "10.1016/j.pan.2022.11.003",
"authors": [
- ["Shanshan", "Huang"],
- ["Su", "Yang"],
- ["Jifeng", "Guo"],
- ["Sen", "Yan"],
- ["Marta A", "Gaertig"],
- ["Shihua", "Li"],
- ["Xiao-Jiang", "Li"]
+ ["Karianne", "Fjeld"],
+ ["Anny", "Gravdal"],
+ ["Ranveig S", "Brekke"],
+ ["Jahedul", "Alam"],
+ ["Steven J", "Wilhelm"],
+ ["Khadija", "El Jellas"],
+ ["Helene N", "Pettersen"],
+ ["Jianguo", "Lin"],
+ ["Marie H", "Solheim"],
+ ["Solrun J", "Steine"],
+ ["Bente B", "Johansson"],
+ ["P\u00e5l R", "Nj\u00f8lstad"],
+ ["Caroline S", "Verbeke"],
+ ["Xunjun", "Xiao"],
+ ["Mark E", "Lowe"],
+ ["Anders", "Molven"]
],
- "publisher": "Cell reports",
- "issn": "2211-1247",
- "date": "2015-09-17",
- "abstract": "In polyglutamine (polyQ) diseases, large polyQ repeats cause juvenile cases with different symptoms than those of adult-onset patients, who carry smaller expanded polyQ repeats. The mechanisms behind the differential pathology mediated by different polyQ repeat lengths remain unknown. By studying knockin mouse models of spinal cerebellar ataxia-17 (SCA17), we found that a large polyQ (105 glutamines) in the TATA-box-binding protein (TBP) preferentially causes muscle degeneration and reduces the expression of muscle-specific genes. Direct expression of TBP with different polyQ repeats in mouse muscle revealed that muscle degeneration is mediated only by the large polyQ repeats. Different polyQ repeats differentially alter TBP's interaction with neuronal and muscle-specific transcription factors. As a result, the large polyQ repeat decreases the association of MyoD with TBP and DNA promoters. Our findings suggest that specific alterations in protein interactions by large polyQ repeats may account for the unique pathology in juvenile polyQ diseases.",
+ "publisher": "Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]",
+ "issn": "1424-3911",
+ "date": "2022-11-09",
+ "abstract": "The CEL gene encodes the digestive enzyme carboxyl ester lipase. CEL-HYB1, a hybrid allele of CEL and its adjacent pseudogene CELP, is a genetic variant suggested to increase the risk of chronic pancreatitis (CP). Our aim was to develop a mouse model for CEL-HYB1 that enables studies of pancreatic disease mechanisms.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26387956"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36379850"
},
{
- "id": "pmid:25672822",
+ "id": "pmid:35583610",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25672822",
- "title": "Trehalose attenuates the gait ataxia and gliosis of spinocerebellar ataxia type 17 mice.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/35583610",
+ "title": "Phenotypic Composition of Commercial Anti-CD19 CAR T Cells Affects In Vivo Expansion and Disease Response in Patients with Large B-cell Lymphoma.",
"type": "article-journal",
- "doi": "10.1007/s11064-015-1530-4",
+ "doi": "10.1158/1078-0432.ccr-22-0164",
"authors": [
- ["Zhi-Zhong", "Chen"],
- ["Chien-Ming", "Wang"],
- ["Guan-Chiun", "Lee"],
- ["Ho-Chiang", "Hsu"],
- ["Tzu-Ling", "Wu"],
- ["Chia-Wei", "Lin"],
- ["Chih-Kang", "Ma"],
- ["Guey-Jen", "Lee-Chen"],
- ["Hei-Jen", "Huang"],
- ["Hsiu Mei", "Hsieh-Li"]
+ ["Chiara", "Monfrini"],
+ ["Federico", "Stella"],
+ ["Vanessa", "Aragona"],
+ ["Martina", "Magni"],
+ ["Silva", "Ljevar"],
+ ["Cristina", "Vella"],
+ ["Eugenio", "Fardella"],
+ ["Annalisa", "Chiappella"],
+ ["Francesca", "Nanetti"],
+ ["Martina", "Pennisi"],
+ ["Anna", "Dodero"],
+ ["Anna", "Guidetti"],
+ ["Paolo", "Corradini"],
+ ["Cristiana", "Carniti"]
],
- "publisher": "Neurochemical research",
- "issn": "1573-6903",
- "date": "2015-02-12",
- "abstract": "Spinocerebellar ataxia type 17 (SCA17) is caused by CAG/CAA repeat expansion on the gene encoding a general transcription factor, TATA-box-binding protein (TBP). The CAG repeat expansion leads to the reduced solubility of polyglutamine TBP and induces aggregate formation. The TBP aggregation, mostly present in the cell nuclei, is distinct from that in most other neurodegenerative diseases, in which the aggregation is formed in cytosol or extracellular compartments. Trehalose is a disaccharide issued by the Food and Drug Administration with a Generally Recognized As Safe status. Lines of evidence suggest trehalose could prevent protein aggregate formation in several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. In this study, we evaluated the therapeutic potential of trehalose on SCA17 using cerebellar primary and organotypic culture systems and a mouse model. Our results showed that TBP nuclear aggregation was significantly decreased in both the primary and slice cultures. Trehalose (4 %) was further supplied in the drinking water of SCA17 transgenic mice. We found both the gait behavior in the footprint analysis and motor coordination in the rotarod task were significantly improved in the trehalose-treated SCA17 mice. The cerebellar weight was increased and the astrocyte gliosis was reduced in SCA17 mice after trehalose treatment. These data suggest that trehalose could be a potential nontoxic treatment for SCA17.",
+ "publisher": "Clinical cancer research : an official journal of the American Association for Cancer Research",
+ "issn": "1557-3265",
+ "date": "2022-08-02",
+ "abstract": "In clinical trials, the expansion and persistence of chimeric antigen receptor (CAR) T cells correlate with therapeutic efficacy. However, properties of CAR T cells that enable their in vivo proliferation have still to be consistently defined and the role of CAR T bag content has never been investigated in a real-life setting.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25672822"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35583610"
},
{
- "id": "pmid:23665119",
+ "id": "pmid:35215948",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23665119",
- "title": "Automated home cage assessment shows behavioral changes in a transgenic mouse model of spinocerebellar ataxia type 17.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/35215948",
+ "title": "High Phenotypic Variation between an In Vitro-Passaged Fowl Adenovirus Serotype 1 (FAdV-1) and Its Virulent Progenitor Strain despite Almost Complete Sequence Identity of the Whole Genomes.",
"type": "article-journal",
- "doi": "10.1016/j.bbr.2013.04.042",
+ "doi": "10.3390/v14020358",
"authors": [
- ["Esteban", "Portal"],
- ["Olaf", "Riess"],
- ["Huu Phuc", "Nguyen"]
+ ["Beatrice", "Grafl"],
+ ["Anna", "Schachner"],
+ ["Michael", "Hess"]
],
- "publisher": "Behavioural brain research",
- "issn": "1872-7549",
- "date": "2013-05-07",
- "abstract": "Spinocerebellar Ataxia type 17 (SCA17) is an autosomal dominantly inherited, neurodegenerative disease characterized by ataxia, involuntary movements, and dementia. A novel SCA17 mouse model having a 71 polyglutamine repeat expansion in the TATA-binding protein (TBP) has shown age related motor deficit using a classic motor test, yet concomitant weight increase might be a confounding factor for this measurement. In this study we used an automated home cage system to test several motor readouts for this same model to confirm pathological behavior results and evaluate benefits of automated home cage in behavior phenotyping. Our results confirm motor deficits in the Tbp/Q71 mice and present previously unrecognized behavioral characteristics obtained from the automated home cage, indicating its use for high-throughput screening and testing, e.g. of therapeutic compounds.",
+ "publisher": "Viruses",
+ "issn": "1999-4915",
+ "date": "2022-02-09",
+ "abstract": "Adenoviral gizzard erosion is an emerging disease with negative impact on health and production of chickens. In this study, we compared in vitro and in vivo characteristics of a fowl adenovirus serotype 1 (FAdV-1), attenuated by 53 consecutive passages in primary chicken embryo liver (CEL) cell cultures (11/7127-AT), with the virulent strain (11/7127-VT). Whole genome analysis revealed near-complete sequence identity between the strains. However, a length polymorphism in a non-coding adenine repeat sequence (11/7127-AT: 11 instead of 9) immediately downstream of the hexon open reading frame was revealed. One-step growth kinetics showed delayed multiplication of 11/7127-AT together with significantly lower titers in cell culture (up to 4 log",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23665119"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35215948"
},
{
- "id": "pmid:23475385",
+ "id": "pmid:35156195",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23475385",
- "title": "From normal gait to loss of ambulation in 6 months: a novel presentation of SCA17.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/35156195",
+ "title": "In Vivo Cellular Expansion of Lisocabtagene Maraleucel and Association With Efficacy and Safety in Relapsed/Refractory Large B-Cell Lymphoma.",
"type": "article-journal",
- "doi": "10.1007/s12311-013-0466-y",
+ "doi": "10.1002/cpt.2561",
"authors": [
- ["R", "Mehanna"],
- ["I", "Itin"]
+ ["Ken", "Ogasawara"],
+ ["James", "Lymp"],
+ ["Timothy", "Mack"],
+ ["Justine", "Dell'Aringa"],
+ ["Chang-Pin", "Huang"],
+ ["Jeff", "Smith"],
+ ["Leanne", "Peiser"],
+ ["Ana", "Kostic"]
],
- "publisher": "Cerebellum (London, England)",
- "issn": "1473-4230",
- "date": "2013-08-01",
- "abstract": "Spinocerebellar ataxias are a group of rare and heterogeneous autosomal dominant disorders characterized by progressive ataxia and other features. Spinocerebellar ataxia 17 (SCA17) is one of the 32 subtypes described to date and is secondary to CAG/CAA repeat expansion in the gene coding for the TATA-box binding protein (TBP). SCA17 is clinically heterogeneous and typically presents with slowly evolving ataxia, dysarthria, dementia, depression, and other movement disorders such as chorea. More than 41 CAG/CAA repeats are considered diagnostic of SCA17, with more than 49 being associated with full penetrance. We report one patient presenting with isolated rapidly evolving ataxia who was found to have 44 CAG/CAA repeats in the TBP gene. This suggests that, while SCA17 typically slowly progresses over years, its repertoire of presentations should be expanded to include rapidly progressive isolated ataxia resembling paraneoplastic disorders or prion disease.",
+ "publisher": "Clinical pharmacology and therapeutics",
+ "issn": "1532-6535",
+ "date": "2022-03-20",
+ "abstract": "Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, chimeric antigen receptor T-cell product for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (LBCL) after 2 or more lines of systemic therapy. In vivo cellular expansion after single-dose administration of liso-cel has been characterized. In this article, in vivo liso-cel expansion in the pivotal study TRANSCEND NHL 001 (ClinicalTrials.gov identifier, NCT02631044) was further characterized to assess the relationship between in vivo cellular expansion after single-dose administration of liso-cel and efficacy or safety after adjusting for key baseline characteristics. Two bioanalytical methods, quantitative polymerase chain reaction and flow cytometry, were used for the assessment of cellular kinetics of liso-cel, which showed high concordance for in vivo cellular expansion. Multivariable logistic regression analyses demonstrated that higher in vivo cellular expansion of liso-cel was associated with a higher overall response and complete response rate, and a higher incidence of cytokine release syndrome and neurological events in patients with relapsed or refractory LBCL. Age and tumor burden (by sum of the product of perpendicular diameters) were likely to confound the relationship between in vivo cellular expansion and efficacy, where the association became stronger after controlling for these factors. Repeat dosing of liso-cel was tested in the study; however, in vivo cellular expansion of liso-cel was lower after repeat dosing than after the initial dose. These findings should enable a comprehensive understanding of the in vivo cellular kinetics of liso-cel and the association with outcomes in relapsed/refractory LBCL.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23475385"
-},
-{
- "id": "pmid:21710129",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/21710129",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:21710129']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35156195"
},
{
- "id": "pmid:21562248",
+ "id": "pmid:35082198",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21562248",
- "title": "Evaluating the prevalence of polyglutamine repeat expansions in amyotrophic lateral sclerosis.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/35082198",
+ "title": "Identification of a Novel Mutation in Carboxyl Ester Lipase Gene in a Patient with MODY-like Diabetes.",
"type": "article-journal",
- "doi": "10.1212/wnl.0b013e31821f4447",
+ "doi": "10.1620/tjem.256.37",
"authors": [
- ["T", "Lee"],
- ["Y R", "Li"],
- ["A", "Chesi"],
- ["M P", "Hart"],
- ["D", "Ramos"],
- ["N", "Jethava"],
- ["D", "Hosangadi"],
- ["J", "Epstein"],
- ["B", "Hodges"],
- ["N M", "Bonini"],
- ["A D", "Gitler"]
+ ["Tomomi", "Kondoh"],
+ ["Yoko", "Nakajima"],
+ ["Katsuyuki", "Yokoi"],
+ ["Yuji", "Matsumoto"],
+ ["Hidehito", "Inagaki"],
+ ["Takema", "Kato"],
+ ["Yoichi", "Nakajima"],
+ ["Tetsuya", "Ito"],
+ ["Tetsushi", "Yoshikawa"],
+ ["Hiroki", "Kurahashi"]
],
- "publisher": "Neurology",
- "issn": "1526-632X",
- "date": "2011-05-11",
- "abstract": "Given the recent finding of an association between intermediate-length polyglutamine (polyQ) expansions in ataxin 2 and amyotrophic lateral sclerosis (ALS), we sought to determine whether expansions in other polyQ disease genes were associated with ALS.",
+ "publisher": "The Tohoku journal of experimental medicine",
+ "issn": "1349-3329",
+ "date": "2022-01-01",
+ "abstract": "Maturity-onset diabetes of the young (MODY) is a form of diabetes mellitus characterized by autosomal dominant inheritance, early onset, and the absence of pancreatic autoimmune markers. MODY-causing mutations have been identified in 14 genes, and carboxyl ester lipase (CEL) has been implicated in MODY8. We report a Japanese patient with MODY who harbored a heterogeneous mutation in CEL exon 2 (NM_001807.4:c.146_147delCT; NP_001798.2:p.Ser49CysfsTer52). A 13-year-old girl experienced her first episode of diabetic ketoacidosis, during which her endogenous insulin secretion was poor. However, her insulin secretion had apparently recovered 2 months after the commencement of insulin treatment, and no further treatment was required for the following 2 years. Diabetic ketoacidosis recurred when the patient was 15 years old, when her insulin secretion was again poor. Since that time, the patient, who is now 18 years old, has been undergoing continuous insulin treatment. The large fluctuations in her insulin secretory capacity led us to suspect MODY. MODY8 patients that carry a mutation in the variable number of tandem repeats in the last exon of the CEL gene typically show pancreatic exocrine dysfunction. However, in the present case, which features premature termination, there is no involvement of exocrine dysfunction, potentially demonstrating a genotype-phenotype correlation.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21562248"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35082198"
},
{
- "id": "pmid:21437269",
+ "id": "pmid:34850019",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21437269",
- "title": "Triplet repeat-derived siRNAs enhance RNA-mediated toxicity in a Drosophila model for myotonic dystrophy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/34850019",
+ "title": "Two New Mutations in the CEL Gene Causing Diabetes and Hereditary Pancreatitis: How to Correctly Identify MODY8 Cases.",
"type": "article-journal",
- "doi": "10.1371/journal.pgen.1001340",
+ "doi": "10.1210/clinem/dgab864",
"authors": [
- ["Zhenming", "Yu"],
- ["Xiuyin", "Teng"],
- ["Nancy M", "Bonini"]
+ ["Khadija", "El Jellas"],
+ ["Petra", "Du\u0161\u00e1tkov\u00e1"],
+ ["Ingfrid S", "Haldorsen"],
+ ["Janne", "Molnes"],
+ ["Erling", "Tjora"],
+ ["Bente B", "Johansson"],
+ ["Karianne", "Fjeld"],
+ ["Stefan", "Johansson"],
+ ["\u0160t\u011bp\u00e1nka", "Pr\u016fhov\u00e1"],
+ ["Leif", "Groop"],
+ ["J Matthias", "L\u00f6hr"],
+ ["P\u00e5l R", "Nj\u00f8lstad"],
+ ["Anders", "Molven"]
],
- "publisher": "PLoS genetics",
- "issn": "1553-7404",
- "date": "2011-03-17",
- "abstract": "More than 20 human neurological and neurodegenerative diseases are caused by simple DNA repeat expansions; among these, non-coding CTG repeat expansions are the basis of myotonic dystrophy (DM1). Recent work, however, has also revealed that many human genes have anti-sense transcripts, raising the possibility that human trinucleotide expansion diseases may be comprised of pathogenic activities due both to a sense expanded-repeat transcript and to an anti-sense expanded-repeat transcript. We established a Drosophila model for DM1 and tested the role of interactions between expanded CTG transcripts and expanded CAG repeat transcripts. These studies revealed dramatically enhanced toxicity in flies co-expressing CTG with CAG expanded repeats. Expression of the two transcripts led to novel pathogenesis with the generation of dcr-2 and ago2-dependent 21-nt triplet repeat-derived siRNAs. These small RNAs targeted the expression of CAG-containing genes, such as Ataxin-2 and TATA binding protein (TBP), which bear long CAG repeats in both fly and man. These findings indicate that the generation of triplet repeat-derived siRNAs may dramatically enhance toxicity in human repeat expansion diseases in which anti-sense transcription occurs.",
+ "publisher": "The Journal of clinical endocrinology and metabolism",
+ "issn": "1945-7197",
+ "date": "2022-03-24",
+ "abstract": "Maturity onset diabetes of the young, type 8 (MODY8) is associated with mutations in the CEL gene, which encodes the digestive enzyme carboxyl ester lipase. Several diabetes cases and families have in recent years been attributed to mutations in CEL without any functional or clinical evidence provided.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21437269"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34850019"
},
{
- "id": "pmid:20587494",
+ "id": "pmid:34507899",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/20587494",
- "title": "Spinocerebellar ataxia type 17 associated with an expansion of 42 glutamine residues in TATA-box binding protein gene.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/34507899",
+ "title": "Homozygosity of short VNTR lengths in the CEL gene may confer susceptibility to idiopathic chronic pancreatitis.",
"type": "article-journal",
- "doi": "10.1136/jnnp.2009.180711",
+ "doi": "10.1016/j.pan.2021.09.001",
"authors": [
- ["D", "Nolte"],
- ["E", "Sobanski"],
- ["A", "Wissen"],
- ["J U", "Regula"],
- ["C", "Lichy"],
- ["U", "M\u00fcller"]
+ ["Xiao-Tong", "Mao"],
+ ["Shun-Jiang", "Deng"],
+ ["Rui-Lin", "Kang"],
+ ["Yuan-Chen", "Wang"],
+ ["Zhao-Shen", "Li"],
+ ["Wen-Bin", "Zou"],
+ ["Zhuan", "Liao"]
],
- "publisher": "Journal of neurology, neurosurgery, and psychiatry",
- "issn": "1468-330X",
- "date": "2010-06-28",
- "abstract": "Spinocerebellar ataxia type 17 (SCA17) is caused by abnormal expansions of CAG/CAA trinucleotides within the TATA-box binding protein gene (TBP). The currently accepted critical threshold of abnormal expansions is \u226543.",
+ "publisher": "Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]",
+ "issn": "1424-3911",
+ "date": "2021-09-04",
+ "abstract": "The carboxyl-ester lipase (CEL) gene contains a variable number of tandem repeats (VNTR) region. It remains unclear whether the number of repeats in the CEL VNTR is related to the risk of pancreatic diseases. The aim of this study was to investigate whether CEL VNTR length is associated with idiopathic chronic pancreatitis (ICP), alcoholic chronic pancreatitis (ACP), or pancreatic cancer in a cohort of Chinese patients.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20587494"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34507899"
},
{
- "id": "pmid:20199210",
+ "id": "pmid:34100900",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/20199210",
- "title": "A spinocerebellar ataxia family with expanded alleles in the TATA-binding protein gene and ataxin-3 gene.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/34100900",
+ "title": "Axicabtagene ciloleucel in vivo expansion and treatment outcome in aggressive B-cell lymphoma in a real-world setting.",
"type": "article-journal",
- "doi": "10.3109/00207450903389149",
+ "doi": "10.1182/bloodadvances.2020003959",
"authors": [
- ["Qian", "Xu"],
- ["Qinghua", "Li"],
- ["Junling", "Wang"],
- ["Hong", "Jiang"],
- ["Lu", "Shen"],
- ["Xiaohui", "Li"],
- ["Beisha", "Tang"]
+ ["Francis A", "Ayuk"],
+ ["Carolina", "Berger"],
+ ["Anita", "Badbaran"],
+ ["Tatjana", "Zabelina"],
+ ["Tanja", "Sonntag"],
+ ["Kristoffer", "Riecken"],
+ ["Maria", "Geffken"],
+ ["Dominic", "Wichmann"],
+ ["Christian", "Frenzel"],
+ ["Guenther", "Thayssen"],
+ ["Silke", "Zeschke"],
+ ["Nicolaus", "Kr\u00f6ger"],
+ ["Boris", "Fehse"]
],
- "publisher": "The International journal of neuroscience",
- "issn": "1563-5279",
- "date": "2010-02-01",
- "abstract": "We report on a Chinese family with three members who have CAG repeat expansion in the ataxin-3, two members present with expanded trinucleotide repeat in both the ataxin-3 and tata-binding protein (TBP) and an individual who carries expanded CAG/CAA repeat in the TBP. Only the patients who carry an allele with expansion in the ataxin-3 gene presented with clinical symptoms. This interesting family presents a unique mutation state. We will continue to track this family in the future, which may help us further elucidate the pathogenic mechanism of spinocerebellar ataxia (SCA) type 3 and 17. The study also provides us a novel conception that mutations from two pathogenetic genes may coexist in one patient and SCA-affected patients with intermediate allele need to be further excluded for other SCA subtypes.",
+ "publisher": "Blood advances",
+ "issn": "2473-9537",
+ "date": "2021-06-08",
+ "abstract": "Data on the association between chimeric antigen receptor (CAR)-T-cell kinetics and patient outcome in the nontrial setting are missing, mainly due to the lack of broadly available CAR-T-cell diagnostic quantification tools. We performed prospective quantification of axicabtagene ciloleucel (axi-cel) in 21 patients treated for aggressive B-cell lymphoma at our clinic. Median peak CAR-T-cell count was 16.14 CAR-T cells/\u00b5L. Patients with 16.14/\u03bcL or higher peak CAR-T cells (strong expanders) had more day-30 objective responses (91% vs 40%, P = .02). In univariate analysis, peak CAR-T cell \u2265 16.14 (P < .001), normal platelet counts at start of lymphodepletion (P < .001), no prior stem cell transplant (P = .04), and peak CAR-T cells as continuous variable (P = .03) were associated with better progression-free survival (PFS). After adjusting for platelet counts and prior stem cell transplantation, peak CAR-T cells below median was still associated with shorter PFS (relative risk, 0.15, 95% confidence interval, 0.04-0.59, P = .007). Low platelet counts also maintained significant impact on PFS. Our data demonstrate association of axi-cel levels and outcome in a nontrial setting and for the first time use a cutoff to segregate weak and strong expanders with respective outcomes.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20199210"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34100900"
},
{
- "id": "pmid:20004653",
+ "id": "pmid:33862081",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/20004653",
- "title": "SCA17 repeat expansion: mildly expanded CAG/CAA repeat alleles in neurological disorders and the functional implications.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/33862081",
+ "title": "The position of single-base deletions in the VNTR sequence of the carboxyl ester lipase (CEL) gene determines proteotoxicity.",
"type": "article-journal",
- "doi": "10.1016/j.cca.2009.12.002",
+ "doi": "10.1016/j.jbc.2021.100661",
"authors": [
- ["Chiung-Mei", "Chen"],
- ["Li-Ching", "Lee"],
- ["Bing-Wen", "Soong"],
- ["Hon-Chung", "Fung"],
- ["Wen-Chuin", "Hsu"],
- ["Pei-Ying", "Lin"],
- ["Hui-Ju", "Huang"],
- ["Fen-Lin", "Chen"],
- ["Cheng-Yueh", "Lin"],
- ["Guey-Jen", "Lee-Chen"],
- ["Yih-Ru", "Wu"]
+ ["Anny", "Gravdal"],
+ ["Xunjun", "Xiao"],
+ ["Miriam", "Cnop"],
+ ["Khadija", "El Jellas"],
+ ["Stefan", "Johansson"],
+ ["P\u00e5l R", "Nj\u00f8lstad"],
+ ["Mark E", "Lowe"],
+ ["Bente B", "Johansson"],
+ ["Anders", "Molven"],
+ ["Karianne", "Fjeld"]
],
- "publisher": "Clinica chimica acta; international journal of clinical chemistry",
- "issn": "1873-3492",
- "date": "2009-12-11",
- "abstract": "Spinocerebellar ataxia type 17 (SCA17) involves the expression of a CAG/CAA expansion mutation in the gene encoding TATA-box binding protein (TBP), a general transcription initiation factor. The spectrum of SCA17 clinical presentation is broad.",
+ "publisher": "The Journal of biological chemistry",
+ "issn": "1083-351X",
+ "date": "2021-04-14",
+ "abstract": "Variable number of tandem repeat (VNTR) sequences in the genome can have functional consequences that contribute to human disease. This is the case for the CEL gene, which is specifically expressed in pancreatic acinar cells and encodes the digestive enzyme carboxyl ester lipase. Rare single-base deletions (DELs) within the first (DEL1) or fourth (DEL4) VNTR segment of CEL cause maturity-onset diabetes of the young, type 8 (MODY8), an inherited disorder characterized by exocrine pancreatic dysfunction and diabetes. Studies on the DEL1 variant have suggested that MODY8 is initiated by CEL protein misfolding and aggregation. However, it is unclear how the position of single-base deletions within the CEL VNTR affects pathogenic properties of the protein. Here, we investigated four naturally occurring CEL variants, arising from single-base deletions in different VNTR segments (DEL1, DEL4, DEL9, and DEL13). When the four variants were expressed in human embryonic kidney 293 cells, only DEL1 and DEL4 led to significantly reduced secretion, increased intracellular aggregation, and increased endoplasmic reticulum stress compared with normal CEL protein. The level of O-glycosylation was affected in all DEL variants. Moreover, all variants had enzymatic activity comparable with that of normal CEL. We conclude that the longest aberrant protein tails, resulting from single-base deletions in the proximal VNTR segments, have highest pathogenic potential, explaining why DEL1 and DEL4 but not DEL9 and DEL13 have been observed in patients with MODY8. These findings further support the view that CEL mutations cause pancreatic disease through protein misfolding and proteotoxicity, leading to endoplasmic reticulum stress and activation of the unfolded protein response.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20004653"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33862081"
},
{
- "id": "pmid:19566714",
+ "id": "pmid:27802312",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/19566714",
- "title": "TATA box-binding protein gene is associated with risk for schizophrenia, age at onset and prefrontal function.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27802312",
+ "title": "Length of Variable Numbers of Tandem Repeats in the Carboxyl Ester Lipase (CEL) Gene May Confer Susceptibility to Alcoholic Liver Cirrhosis but Not Alcoholic Chronic Pancreatitis.",
"type": "article-journal",
- "doi": "10.1111/j.1601-183x.2009.00497.x",
+ "doi": "10.1371/journal.pone.0165567",
"authors": [
- ["K", "Ohi"],
- ["R", "Hashimoto"],
- ["Y", "Yasuda"],
- ["M", "Kiribayashi"],
- ["N", "Iike"],
- ["T", "Yoshida"],
- ["M", "Azechi"],
- ["K", "Ikezawa"],
- ["H", "Takahashi"],
- ["T", "Morihara"],
- ["R", "Ishii"],
- ["S", "Tagami"],
- ["M", "Iwase"],
- ["M", "Okochi"],
- ["K", "Kamino"],
- ["H", "Kazui"],
- ["T", "Tanaka"],
- ["T", "Kudo"],
- ["M", "Takeda"]
+ ["Karianne", "Fjeld"],
+ ["Sebastian", "Beer"],
+ ["Marianne", "Johnstone"],
+ ["Constantin", "Zimmer"],
+ ["Joachim", "M\u00f6ssner"],
+ ["Claudia", "Ruffert"],
+ ["Mario", "Krehan"],
+ ["Christian", "Zapf"],
+ ["P\u00e5l Rasmus", "Nj\u00f8lstad"],
+ ["Stefan", "Johansson"],
+ ["Peter", "Bugert"],
+ ["Fabio", "Miyajima"],
+ ["Triantafillos", "Liloglou"],
+ ["Laura J", "Brown"],
+ ["Simon A", "Winn"],
+ ["Kelly", "Davies"],
+ ["Diane", "Latawiec"],
+ ["Bridget K", "Gunson"],
+ ["David N", "Criddle"],
+ ["Munir", "Pirmohamed"],
+ ["Robert", "Gr\u00fctzmann"],
+ ["Patrick", "Michl"],
+ ["William", "Greenhalf"],
+ ["Anders", "Molven"],
+ ["Robert", "Sutton"],
+ ["Jonas", "Rosendahl"]
],
- "publisher": "Genes, brain, and behavior",
- "issn": "1601-183X",
- "date": "2009-06-01",
- "abstract": "Schizophrenia is a common polygenic disease in distinct populations, while spinocerebellar ataxia type 17 (SCA17) is a rare autosomal dominant neurodegenerative disorder. Both diseases involve psychotic symptoms. SCA17 is caused by an expanded polyglutamine tract in the TATA box-binding protein (TBP) gene. In the present study, we investigated the association between schizophrenia and CAG repeat length in common TBP alleles with fewer than 42 CAG repeats in a Japanese population (326 patients with schizophrenia and 116 healthy controls). We found that higher frequency of alleles with greater than 35 CAG repeats in patients with schizophrenia compared with that in controls (p = 0.042). We also examined the correlation between CAG repeats length and age at onset of schizophrenia. We observed a negative correlation between the number of CAG repeats in the chromosome with longer CAG repeats out of two chromosomes and age at onset of schizophrenia (p = 0.020). We further provided evidence that TBP genotypes with greater than 35 CAG repeats, which were enriched in patients with schizophrenia, were significantly associated with hypoactivation of the prefrontal cortex measured by near-infrared spectroscopy during the tower of Hanoi, a task of executive function (right PFC; p = 0.015, left PFC; p = 0.010). These findings suggest possible associations of the genetic variations of the TBP gene with risk for schizophrenia, age at onset and prefrontal function.",
+ "publisher": "PloS one",
+ "issn": "1932-6203",
+ "date": "2016-11-01",
+ "abstract": "Carboxyl-ester lipase (CEL) contributes to fatty acid ethyl ester metabolism, which is implicated in alcoholic pancreatitis. The CEL gene harbours a variable number of tandem repeats (VNTR) region in exon 11. Variation in this VNTR has been linked to monogenic pancreatic disease, while conflicting results were reported for chronic pancreatitis (CP). Here, we aimed to investigate a potential association of CEL VNTR lengths with alcoholic CP.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19566714"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27802312"
},
{
- "id": "pmid:18218637",
+ "id": "pmid:27650499",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/18218637",
- "title": "Polyglutamine expansion reduces the association of TATA-binding protein with DNA and induces DNA binding-independent neurotoxicity.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27650499",
+ "title": "A Carboxyl Ester Lipase (CEL) Mutant Causes Chronic Pancreatitis by Forming Intracellular Aggregates That Activate Apoptosis.",
"type": "article-journal",
- "doi": "10.1074/jbc.m709674200",
+ "doi": "10.1074/jbc.m116.734384",
"authors": [
- ["Meyer J", "Friedman"],
- ["Chuan-En", "Wang"],
- ["Xiao-Jiang", "Li"],
- ["Shihua", "Li"]
+ ["Xunjun", "Xiao"],
+ ["Gabrielle", "Jones"],
+ ["Wednesday A", "Sevilla"],
+ ["Donna B", "Stolz"],
+ ["Kelsey E", "Magee"],
+ ["Margaret", "Haughney"],
+ ["Amitava", "Mukherjee"],
+ ["Yan", "Wang"],
+ ["Mark E", "Lowe"]
],
"publisher": "The Journal of biological chemistry",
- "issn": "0021-9258",
- "date": "2008-01-24",
- "abstract": "TATA-binding protein (TBP) is essential for eukaryotic gene transcription. Human TBP contains a polymorphic polyglutamine (polyQ) domain in its N terminus and a DNA-binding domain in its highly conserved C terminus. Expansion of the polyQ domain to >42 glutamines typically results in spinocerebellar ataxia type 17 (SCA17), a neurodegenerative disorder that resembles Huntington disease. Our recent studies have demonstrated that polyQ expansion causes abnormal interaction of TBP with the general transcription factor TFIIB and induces neurodegeneration in transgenic SCA17 mice (Friedman, M. J., Shah, A. G., Fang, Z. H., Ward, E. G., Warren, S. T., Li, S., and Li, X. J. (2007) Nat. Neurosci. 10, 1519-1528). However, it remains unknown how polyQ expansion influences DNA binding by TBP. Here we report that polyQ expansion reduces in vitro binding of TBP to DNA and that mutant TBP fragments lacking an intact C-terminal DNA-binding domain are present in transgenic SCA17 mouse brains. polyQ-expanded TBP with a deletion spanning part of the DNA-binding domain does not bind DNA in vitro but forms nuclear aggregates and inhibits TATA-dependent transcription activity in cultured cells. When this TBP double mutant is expressed in transgenic mice, it forms nuclear inclusions in neurons and causes early death. These findings suggest that the polyQ tract affects the binding of TBP to promoter DNA and that polyQ-expanded TBP can induce neuronal toxicity independent of its interaction with DNA.",
+ "issn": "1083-351X",
+ "date": "2016-09-20",
+ "abstract": "Patients with chronic pancreatitis (CP) frequently have genetic risk factors for disease. Many of the identified genes have been connected to trypsinogen activation or trypsin inactivation. The description of CP in patients with mutations in the variable number of tandem repeat (VNTR) domain of carboxyl ester lipase (CEL) presents an opportunity to study the pathogenesis of CP independently of trypsin pathways. We tested the hypothesis that a deletion and frameshift mutation (C563fsX673) in the CEL VNTR causes CP through proteotoxic gain-of-function activation of maladaptive cell signaling pathways including cell death pathways. HEK293 or AR42J cells were transfected with constructs expressing CEL with 14 repeats in the VNTR (CEL14R) or C563fsX673 CEL (CEL maturity onset diabetes of youth with a deletion mutation in the VNTR (MODY)). In both cell types, CEL MODY formed intracellular aggregates. Secretion of CEL MODY was decreased compared with that of CEL14R. Expression of CEL MODY increased endoplasmic reticulum stress, activated the unfolded protein response, and caused cell death by apoptosis. Our results demonstrate that disorders of protein homeostasis can lead to CP and suggest that novel therapies to decrease the intracellular accumulation of misfolded protein may be successful in some patients with CP.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18218637"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27650499"
},
{
- "id": "pmid:17033685",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/17033685",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:17033685']' timed out after 3 seconds"
+ "id": "pmid:27773618",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27773618",
+ "title": "Copy number variants and VNTR length polymorphisms of the carboxyl-ester lipase (CEL) gene as risk factors in pancreatic cancer.",
+ "type": "article-journal",
+ "doi": "10.1016/j.pan.2016.10.006",
+ "authors": [
+ ["Monica", "Dalva"],
+ ["Khadija", "El Jellas"],
+ ["Solrun J", "Steine"],
+ ["Bente B", "Johansson"],
+ ["Monika", "Ringdal"],
+ ["Janniche", "Torsvik"],
+ ["Heike", "Immervoll"],
+ ["Dag", "Hoem"],
+ ["Felix", "Laemmerhirt"],
+ ["Peter", "Simon"],
+ ["Markus M", "Lerch"],
+ ["Stefan", "Johansson"],
+ ["P\u00e5l R", "Nj\u00f8lstad"],
+ ["Frank U", "Weiss"],
+ ["Karianne", "Fjeld"],
+ ["Anders", "Molven"]
+ ],
+ "publisher": "Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]",
+ "issn": "1424-3911",
+ "date": "2016-10-11",
+ "abstract": "We have recently described copy number variants (CNVs) of the human carboxyl-ester lipase (CEL) gene, including a recombined deletion allele (CEL-HYB) that is a genetic risk factor for chronic pancreatitis. Associations with pancreatic disease have also been reported for the variable number of tandem repeat (VNTR) region located in CEL exon 11. Here, we examined if CEL CNVs and VNTR length polymorphisms affect the risk for developing pancreatic cancer.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27773618"
},
{
- "id": "pmid:16223509",
+ "id": "pmid:23395566",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/16223509",
- "title": "Minimum prevalence of spinocerebellar ataxia 17 in the north east of England.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23395566",
+ "title": "The number of tandem repeats in the carboxyl-ester lipase (CEL) gene as a risk factor in alcoholic and idiopathic chronic pancreatitis.",
"type": "article-journal",
- "doi": "10.1016/j.jns.2005.08.009",
+ "doi": "10.1016/j.pan.2012.12.059",
"authors": [
- ["Kate", "Craig"],
- ["Sharon M", "Keers"],
- ["Timothy J", "Walls"],
- ["Anne", "Curtis"],
- ["Patrick F", "Chinnery"]
+ ["Anja", "Ragvin"],
+ ["Karianne", "Fjeld"],
+ ["F Ulrich", "Weiss"],
+ ["Janniche", "Torsvik"],
+ ["Ali", "Aghdassi"],
+ ["Julia", "Mayerle"],
+ ["Peter", "Simon"],
+ ["P\u00e5l R", "Nj\u00f8lstad"],
+ ["Markus M", "Lerch"],
+ ["Stefan", "Johansson"],
+ ["Anders", "Molven"]
],
- "publisher": "Journal of the neurological sciences",
- "issn": "0022-510X",
- "date": "2005-10-11",
- "abstract": "To determine the minimum prevalence of spinocerebellar ataxia type 17 (SCA17) in the north east of England.",
+ "publisher": "Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]",
+ "issn": "1424-3911",
+ "date": "2012-12-20",
+ "abstract": "The variable number of tandem repeats (VNTR) in the last exon of the carboxyl-ester lipase (CEL) gene has been reported to associate with alcohol-induced chronic pancreatitis (ACP) in a Japanese study. Here, we have investigated the association between the number of CEL VNTR repeats and ACP or idiopathic chronic pancreatitis (ICP) in a cohort of German patients.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16223509"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23395566"
},
{
- "id": "pmid:15850778",
+ "id": "pmid:21784842",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/15850778",
- "title": "No evidence for association of the TATA-box binding protein glutamine repeat sequence or the flanking chromosome 6q27 region with type 1 diabetes.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21784842",
+ "title": "Diabetes and pancreatic exocrine dysfunction due to mutations in the carboxyl ester lipase gene-maturity onset diabetes of the young (CEL-MODY): a protein misfolding disease.",
"type": "article-journal",
- "doi": "10.1016/j.bbrc.2005.03.203",
+ "doi": "10.1074/jbc.m111.222679",
"authors": [
- ["Felicity", "Payne"],
- ["Deborah J", "Smyth"],
- ["Rebecca", "Pask"],
- ["Jason D", "Cooper"],
- ["Jennifer", "Masters"],
- ["William Y S", "Wang"],
- ["Lisa M", "Godfrey"],
- ["Georgina", "Bowden"],
- ["Jeffrey", "Szeszko"],
- ["Luc J", "Smink"],
- ["Alex C", "Lam"],
- ["Oliver", "Burren"],
- ["Neil M", "Walker"],
- ["Sarah", "Nutland"],
- ["Helen", "Rance"],
- ["Dag E", "Undlien"],
- ["Kjersti S", "R\u00f8nningen"],
- ["Cristian", "Guja"],
- ["Constantin", "Ionescu-T\u00eergovi\u015fte"],
- ["John A", "Todd"],
- ["Rebecca C J", "Twells"]
+ ["Bente B", "Johansson"],
+ ["Janniche", "Torsvik"],
+ ["Lise", "Bj\u00f8rkhaug"],
+ ["Mette", "Vesterhus"],
+ ["Anja", "Ragvin"],
+ ["Erling", "Tjora"],
+ ["Karianne", "Fjeld"],
+ ["Dag", "Hoem"],
+ ["Stefan", "Johansson"],
+ ["Helge", "R\u00e6der"],
+ ["Susanne", "Lindquist"],
+ ["Olle", "Hernell"],
+ ["Miriam", "Cnop"],
+ ["Jaakko", "Saraste"],
+ ["Torgeir", "Flatmark"],
+ ["Anders", "Molven"],
+ ["P\u00e5l R", "Nj\u00f8lstad"]
],
- "publisher": "Biochemical and biophysical research communications",
- "issn": "0006-291X",
- "date": "2005-06-03",
- "abstract": "Susceptibility to the autoimmune disease type 1 diabetes has been linked to human chromosome 6q27 and, moreover, recently associated with one of the genes in the region, TATA box-binding protein (TBP). Using a much larger sample of T1D families than those studied by others, and by extensive re-sequencing of nine other genes in the proximity, in which we identified 279 polymorphisms, 83 of which were genotyped in up to 725 T1D multiplex and simplex families, we obtained no evidence for association of the TBP CAG/CAA (glutamine) microsatellite repeat sequence with disease, or for nine other genes, PDCD2, PSMB1, KIAA1838, DLL1, dJ894D12.4, FLJ25454, FLJ13162, FLJ11152, PHF10 and CCR6. This study also provides an exon-based tag single nucleotide polymorphism map for these 10 genes that can be used for analysis of other diseases.",
+ "publisher": "The Journal of biological chemistry",
+ "issn": "1083-351X",
+ "date": "2011-07-22",
+ "abstract": "CEL-maturity onset diabetes of the young (MODY), diabetes with pancreatic lipomatosis and exocrine dysfunction, is due to dominant frameshift mutations in the acinar cell carboxyl ester lipase gene (CEL). As Cel knock-out mice do not express the phenotype and the mutant protein has an altered and intrinsically disordered tandem repeat domain, we hypothesized that the disease mechanism might involve a negative effect of the mutant protein. In silico analysis showed that the pI of the tandem repeat was markedly increased from pH 3.3 in wild-type (WT) to 11.8 in mutant (MUT) human CEL. By stably overexpressing CEL-WT and CEL-MUT in HEK293 cells, we found similar glycosylation, ubiquitination, constitutive secretion, and quality control of the two proteins. The CEL-MUT protein demonstrated, however, a high propensity to form aggregates found intracellularly and extracellularly. Different physicochemical properties of the intrinsically disordered tandem repeat domains of WT and MUT proteins may contribute to different short and long range interactions with the globular core domain and other macromolecules, including cell membranes. Thus, we propose that CEL-MODY is a protein misfolding disease caused by a negative gain-of-function effect of the mutant proteins in pancreatic tissues.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15850778"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21784842"
},
{
- "id": "pmid:15503103",
+ "id": "pmid:15841033",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/15503103",
- "title": "Mutation at the SCA17 locus is not a common cause of primary dystonia.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15841033",
+ "title": "Carboxylester lipase gene polymorphism as a risk of alcohol-induced pancreatitis.",
"type": "article-journal",
- "doi": "10.1007/s00415-004-0520-2",
+ "doi": "10.1097/01.mpa.0000160960.21580.ml",
"authors": [
- ["Kathrin", "Grundmann"],
- ["Ulrike", "Laubis-Herrmann"],
- ["Dirk", "Dressler"],
- ["Juliane", "Vollmer-Haase"],
- ["Peter", "Bauer"],
- ["Manfred", "Stuhrmann"],
- ["Thorsten", "Schulte"],
- ["Ludger", "Sch\u00f6ls"],
- ["Helge", "Topka"],
- ["Olaf", "Riess"]
+ ["Kyoko", "Miyasaka"],
+ ["Minoru", "Ohta"],
+ ["Saeko", "Takano"],
+ ["Hiroshi", "Hayashi"],
+ ["Susumu", "Higuchi"],
+ ["Katsuya", "Maruyama"],
+ ["Yusuke", "Tando"],
+ ["Teruo", "Nakamura"],
+ ["Yutaka", "Takata"],
+ ["Akihiro", "Funakoshi"]
+ ],
+ "publisher": "Pancreas",
+ "issn": "1536-4828",
+ "date": "2005-05-01",
+ "abstract": "Alcohol abuse causes pancreatic damage in humans. However, only 5% of alcoholic patients have a clinical manifestation of pancreatitis, and the genetic predisposition of alcohol-associated pancreatitis remains elusive. Nonoxidative metabolites of ethanol, fatty acid ethyl esters (FAEEs), might play an important role in pancreatic damage. Carboxylester lipase (CEL) has been known to catalyze FAEE synthesis from fatty acids and ethanol.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15841033"
+},
+{
+ "id": "pmid:27080129",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/27080129",
+ "title": "Manifestation of Huntington's disease pathology in human induced pluripotent stem cell-derived neurons.",
+ "type": "article-journal",
+ "doi": "10.1186/s13024-016-0092-5",
+ "authors": [
+ ["Evgeny D", "Nekrasov"],
+ ["Vladimir A", "Vigont"],
+ ["Sergey A", "Klyushnikov"],
+ ["Olga S", "Lebedeva"],
+ ["Ekaterina M", "Vassina"],
+ ["Alexandra N", "Bogomazova"],
+ ["Ilya V", "Chestkov"],
+ ["Tatiana A", "Semashko"],
+ ["Elena", "Kiseleva"],
+ ["Lyubov A", "Suldina"],
+ ["Pavel A", "Bobrovsky"],
+ ["Olga A", "Zimina"],
+ ["Maria A", "Ryazantseva"],
+ ["Anton Yu", "Skopin"],
+ ["Sergey N", "Illarioshkin"],
+ ["Elena V", "Kaznacheyeva"],
+ ["Maria A", "Lagarkova"],
+ ["Sergey L", "Kiselev"]
],
- "publisher": "Journal of neurology",
- "issn": "0340-5354",
- "date": "2004-10-01",
- "abstract": "Spinocerebellar ataxia type 17 (SCA17) is a dominant progressive neurodegenerative disorder, caused by a triplet repeat expansion within the TATA-binding protein. As well as ataxia and dementia, Parkinsonism and dystonia are common in SCA17. In some pedigrees focal dystonia in the absence of ataxia has been described as a main clinical feature. To evaluate the relevance of SCA17 mutations for primary dystonia, we examined the TBP repeat expansion in a series of 288 patients with different subtypes of primary torsion dystonia. We did not find any repeat sizes in the pathogenic range. We conclude that the SCA17 repeat expansion is not a common cause of familial and sporadic dystonia.",
+ "publisher": "Molecular neurodegeneration",
+ "issn": "1750-1326",
+ "date": "2016-04-14",
+ "abstract": "Huntington's disease (HD) is an incurable hereditary neurodegenerative disorder, which manifests itself as a loss of GABAergic medium spiny (GABA MS) neurons in the striatum and caused by an expansion of the CAG repeat in exon 1 of the huntingtin gene. There is no cure for HD, existing pharmaceutical can only relieve its symptoms.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15503103"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27080129"
},
{
- "id": "pmid:15381080",
+ "id": "pmid:19249009",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/15381080",
- "title": "Association of a CAG/CAA repeat sequence in the TBP gene with type I diabetes.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19249009",
+ "title": "CAG expansion in the Huntington disease gene is associated with a specific and targetable predisposing haplogroup.",
"type": "article-journal",
- "doi": "10.1016/j.bbrc.2004.08.159",
+ "doi": "10.1016/j.ajhg.2009.02.003",
"authors": [
- ["David", "Owerbach"],
- ["Lazaro", "Pi\u00f1a"],
- ["Kenneth H", "Gabbay"]
+ ["Simon C", "Warby"],
+ ["Alexandre", "Montpetit"],
+ ["Anna R", "Hayden"],
+ ["Jeffrey B", "Carroll"],
+ ["Stefanie L", "Butland"],
+ ["Henk", "Visscher"],
+ ["Jennifer A", "Collins"],
+ ["Alicia", "Semaka"],
+ ["Thomas J", "Hudson"],
+ ["Michael R", "Hayden"]
],
- "publisher": "Biochemical and biophysical research communications",
- "issn": "0006-291X",
- "date": "2004-10-22",
- "abstract": "Type I diabetes is a complex disease in which multiple susceptibility loci have been implicated by whole genome scans. IDDM8, a susceptibility locus, is located on chromosome 6q27, however the specific susceptibility gene has yet to be identified. We have examined five potential candidate genes using 36 genetic markers, spanning 360kb located near the chromosome 6q27 terminus in 478 families for diabetes association. No associations with type I diabetes susceptibility were detected with the strength previously observed for IDDM1 or IDDM2. However, a novel CAG/CAA polymorphism was detected in exon 3 of the TATA box-binding protein gene, which shows preliminary evidence of association with diabetes susceptibility (p<0.05).",
+ "publisher": "American journal of human genetics",
+ "issn": "1537-6605",
+ "date": "2009-02-26",
+ "abstract": "Huntington disease (HD) is an autosomal-dominant disorder that results from >or=36 CAG repeats in the HD gene (HTT). Approximately 10% of patients inherit a chromosome that underwent CAG expansion from an unaffected parent with <36 CAG repeats. This study is a comprehensive analysis of genetic diversity in HTT and reveals that HD patients of European origin (n = 65) have a significant enrichment (95%) of a specific set of 22 tagging single nucleotide polymorphisms (SNPs) that constitute a single haplogroup. The disease association of many SNPs is much stronger than any previously reported polymorphism and was confirmed in a replication cohort (n = 203). Importantly, the same haplogroup is also significantly enriched (83%) in individuals with 27-35 CAG repeats (intermediate alleles, n = 66), who are unaffected by the disease, but have increased CAG tract sizes relative to the general population (n = 116). These data support a stepwise model for CAG expansion into the affected range (>or=36 CAG) and identifies specific haplogroup variants in the general population associated with this instability. The specific variants at risk for CAG expansion are not present in the general population in China, Japan, and Nigeria where the prevalence of HD is much lower. The current data argue that cis-elements have a major predisposing influence on CAG instability in HTT. The strong association between specific SNP alleles and CAG expansion also provides an opportunity of personalized therapeutics in HD where the clinical development of only a small number of allele-specific targets may be sufficient to treat up to 88% of the HD patient population.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15381080"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19249009"
},
{
- "id": "pmid:14985389",
+ "id": "pmid:15496421",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/14985389",
- "title": "Trinucleotide repeat expansion in SCA17/TBP in white patients with Huntington's disease-like phenotype.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15496421",
+ "title": "Somatic deletion events occur during early embryonic development and modify the extent of CAG expansion in subsequent generations.",
"type": "article-journal",
- "doi": "10.1136/jmg.2003.015602",
+ "doi": "10.1093/hmg/ddh325",
"authors": [
- ["P", "Bauer"],
- ["F", "Laccone"],
- ["A", "Rolfs"],
- ["U", "W\u00fcllner"],
- ["S", "B\u00f6sch"],
- ["H", "Peters"],
- ["S", "Liebscher"],
- ["M", "Scheible"],
- ["J T", "Epplen"],
- ["B H F", "Weber"],
- ["E", "Holinski-Feder"],
- ["H", "Weirich-Schwaiger"],
- ["D J", "Morris-Rosendahl"],
- ["J", "Andrich"],
- ["O", "Riess"]
+ ["I V", "Kovtun"],
+ ["A R", "Thornhill"],
+ ["C T", "McMurray"]
],
- "publisher": "Journal of medical genetics",
- "issn": "1468-6244",
- "date": "2004-03-01",
- "abstract": "",
+ "publisher": "Human molecular genetics",
+ "issn": "0964-6906",
+ "date": "2004-10-20",
+ "abstract": "Alterations in trinucleotide repeat length during transmission are important in the pathophysiology of Huntington's disease (HD). However, it is not well understood where, when and by what mechanism expansion occurs. We have followed the fate of CAG repeats during development in mice that can [hHD(-/+)/Msh2(+/+)] or cannot [hHD(-/+)/Msh2(-/-)] expand their repeats. Here we show that long repeats are shortened during somatic replication early in the embryo of the progeny. Our data point to different mechanisms for expansion and deletion. Deletions arise during replication, do not depend on the presence of Msh2 and are largely restricted to early development. In contrast, expansions depend on strand break repair, require the presence of Msh2 and occur later in development. Overall, these results suggest that deletions in early development serve as a safeguard of the genome and protect against expansion of the disease-range repeats during transmission.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:14985389"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15496421"
},
{
- "id": "pmid:12953269",
+ "id": "pmid:15229244",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/12953269",
- "title": "Clinical features and neuropathology of autosomal dominant spinocerebellar ataxia (SCA17).",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15229244",
+ "title": "YB-1 and CTCF differentially regulate the 5-HTT polymorphic intron 2 enhancer which predisposes to a variety of neurological disorders.",
"type": "article-journal",
- "doi": "10.1002/ana.10676",
+ "doi": "10.1523/jneurosci.1150-04.2004",
"authors": [
- ["Arndt", "Rolfs"],
- ["Arnulf H", "Koeppen"],
- ["Ingrid", "Bauer"],
- ["Peter", "Bauer"],
- ["Sven", "Buhlmann"],
- ["Helge", "Topka"],
- ["Ludger", "Sch\u00f6ls"],
- ["Olaf", "Riess"]
+ ["Elena", "Klenova"],
+ ["Alison C", "Scott"],
+ ["Julian", "Roberts"],
+ ["Shaharum", "Shamsuddin"],
+ ["Elizabeth A", "Lovejoy"],
+ ["Stephan", "Bergmann"],
+ ["Vivien J", "Bubb"],
+ ["Hans-Dieter", "Royer"],
+ ["John P", "Quinn"]
],
- "publisher": "Annals of neurology",
- "issn": "0364-5134",
- "date": "2003-09-01",
- "abstract": "Autosomal dominant spinocerebellar ataxias (SCAs) are a group of neurodegenerative disorders clinically characterized by late-onset ataxia and variable other manifestations. Genetically and clinically, SCA is highly heterogeneous. Recently, CAG repeat expansions in the gene encoding TATA-binding protein (TBP) have been found in a new form of SCA, which has been designated SCA17. To estimate the frequency of SCA17 among white SCA patients and to define the phenotypic variability, we determined the frequency of SCA17 in a large sample of 1,318 SCA patients. In total, 15 patients in four autosomal dominant SCA families had CAG/CAA repeat expansions in the TBP gene ranging from 45 to 54 repeats. The clinical features of our SCA17 patients differ from other SCA types by manifesting with psychiatric abnormalities and dementia. The neuropathology of SCA17 can be classified as a \"pure cerebellar\" or \"cerebello-olivary\" form of ataxia. However, intranuclear neuronal inclusion bodies with immunoreactivity to anti-TBP and antipolyglutamine were much more widely distributed throughout the brain gray matter than in other SCAs. Based on clinical and genetic data, we conclude that SCA17 is rare among white SCA patients. SCA17 should be considered in sporadic and familial cases of ataxia with accompanying psychiatric symptoms and dementia.",
+ "publisher": "The Journal of neuroscience : the official journal of the Society for Neuroscience",
+ "issn": "1529-2401",
+ "date": "2004-06-30",
+ "abstract": "The serotonin transporter (5-HTT) gene contains a variable number tandem repeat (VNTR) domain within intron 2 that is often associated with a number of neurological conditions, including affective disorders. The implications of this polymorphism are not yet understood, however, we have previously demonstrated that the 5-HTT VNTR is a transcriptional regulatory domain, and the allelic variation supports differential reporter gene expression in vivo and in vitro. The aim of this study was to identify transcription factors responsible for the regulation of this VNTR. Using a yeast one-hybrid screen, we found the transcription factor Y box binding protein 1 (YB-1) interacts with the 5-HTT VNTR. Consistent with this, we demonstrate in a reporter gene assay that the polymorphic VNTR domains differentially respond to exogenous YB-1 and that YB-1 will bind to the VNTR in vitro in a sequence-specific manner. Interestingly, the transcription factor CCTC-binding factor (CTCF), previously shown to interact with YB-1, interferes with the ability of the VNTR to support YB-1-directed reporter gene expression. In addition, CTCF blocks the binding of YB-1 to its DNA recognition sequences in vitro, thus providing a possible mechanism of regulation of YB-1 activation of the VNTR by CTCF. Therefore, we have identified YB-1 and CTCF as transcription factors responsible, at least in part, for modulation of VNTR function as a transcriptional regulatory domain. Our data suggest a novel mechanism that explains, in part, the ability of the distinct VNTR copy numbers to support differential reporter gene expression based on YB-1 binding sites.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15229244"
+},
+{
+ "id": "pmid:14625025",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/14625025",
+ "title": "Polymorphisms within the promoter and the intron 2 of the serotonin transporter gene in a population of bulimic patients.",
+ "type": "article-journal",
+ "doi": "10.1016/j.neulet.2003.08.058",
+ "authors": [
+ ["N", "Lauzurica"],
+ ["A", "Hurtado"],
+ ["A", "Escart\u00ed"],
+ ["M", "Delgado"],
+ ["V", "Barrios"],
+ ["G", "Morand\u00e9"],
+ ["J", "Soriano"],
+ ["I", "J\u00e1uregui"],
+ ["M I", "Gonz\u00e1lez-Valdemoro"],
+ ["E", "Garc\u00eda-Camba"],
+ ["J A", "Fuentes"]
+ ],
+ "publisher": "Neuroscience letters",
+ "issn": "0304-3940",
+ "date": "2003-12-11",
+ "abstract": "The serotonin transporter (5-HTT) gene is a firm candidate to explain eating disorders. In this association study, two different polymorphisms were analysed: a variable number of tandem repeat (VNTR) polymorphism in intron 2 and a deletion/insertion polymorphism (5-HTTLPR) in the promoter region. The hypothesis that these gene polymorphisms may be a susceptibility factor in bulimia nervosa (BN) was explored in a female population of 102 purgative bulimics. BN patients who have suffered preceding anorexia nervosa (AN) episodes formed the so-called previous AN bulimic patient group. In our sample of normal-eater controls and purging type bulimics, regardless of whether or not the BN patients had suffered prior AN episodes, no differences were found considering the frequencies of genotypes, alleles or haplotypes of both polymorphic regions of the 5-HTT gene.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12953269"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:14625025"
},
{
- "id": "pmid:12891385",
+ "id": "pmid:12700167",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/12891385",
- "title": "SCA17 caused by homozygous repeat expansion in TBP due to partial isodisomy 6.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/12700167",
+ "title": "Raised intracellular glucose concentrations reduce aggregation and cell death caused by mutant huntingtin exon 1 by decreasing mTOR phosphorylation and inducing autophagy.",
"type": "article-journal",
- "doi": "10.1038/sj.ejhg.5201018",
+ "doi": "10.1093/hmg/ddg109",
"authors": [
- ["C H", "Z\u00fchlke"],
- ["M", "Spranger"],
- ["S", "Spranger"],
- ["R", "Voigt"],
- ["M", "Lanz"],
- ["U", "Gehlken"],
- ["F", "Hinrichs"],
- ["E", "Schwinger"]
+ ["Brinda", "Ravikumar"],
+ ["Abigail", "Stewart"],
+ ["Hiroko", "Kita"],
+ ["Kikuya", "Kato"],
+ ["Rainer", "Duden"],
+ ["David C", "Rubinsztein"]
],
- "publisher": "European journal of human genetics : EJHG",
- "issn": "1018-4813",
- "date": "2003-08-01",
- "abstract": "An expanded polyglutamine domain in the TATA-binding protein (TBP) has been described in patients with spinocerebellar ataxia type 17 (SCA17) characterized by cerebellar ataxia associated with dementia. TBP is a general transcription initiation factor that regulates the expression of most eukaryotic genes transcribed by RNA polymerase II. SCA17, as an autosomal dominantly inherited progressive neurodegenerative disorder, is caused by heterozygous expansion of a CAG repeat coding for glutamine. Alleles with 27 to a maximum of 44 glutamine residues were found as the normal range, whereas expansions above 45 repeat units were considered pathological. Here, we present a patient with a very severe phenotype with a late onset but rapidly progressing ataxia associated with dementia and homozygous 47 glutamine residues caused by an apparent partial isodisomy 6. This extraordinary case has important implications for the insights of TBP and SCA17. The expanded polyglutamine domain in both TBP copies is not correlated with embryonic death indicating that the normal function of the protein is not disrupted by this kind of mutation but may account for the dementia seen in this patient.",
+ "publisher": "Human molecular genetics",
+ "issn": "0964-6906",
+ "date": "2003-05-01",
+ "abstract": "Huntington's disease is caused by a CAG trinucleotide repeat expansion that is translated into an abnormally long polyglutamine tract. This gain-of-function mutation is associated with huntingtin aggregation and cell death. Autophagy is an important clearance route for mutant huntingtin exon 1. While mammalian target of rapamycin (mTOR) is a key regulator of autophagy, the upstream modifiers of this process are poorly understood. Our previous expression profiling studies in HD cell models observed changes in four genes associated with glucose metabolism, including the GLUT1 glucose transporter. A role for intracellular glucose as a modulator for polyglutamine toxicity was suggested as cell death was reduced by GLUT1 overexpression. Here we show that the protective effect of GLUT1 is associated with decreased huntingtin exon 1 aggregation in cell models. Consistent with this result, we also observed reduced aggregation and enhanced clearance of mutant huntingtin when cells were cultured in raised glucose concentrations (8 g/l). These effects were mimicked by 8 g/l 2-deoxyglucose (2DOG) (transported, phosphorylated but not metabolized further), but not with 8 g/l 3-O-methyl glucose (transported but not metabolized further). Thus, this phenomenon is probably mediated by glucose-6-phosphate. Increased clearance of mutant huntingtin by raised glucose (8 g/l) and 2DOG correlated with increased autophagy and reduced phosphorylation of mTOR, S6K1 and Akt. Thus, raised intracellular glucose/glucose 6-phosphate levels reduce mutant huntingtin toxicity by increasing autophagy via mTOR and possibly Akt. As mTOR and Akt regulate a diversity of crucial cellular processes, our data also suggest a major new set of targets for intracellular glucose signalling.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12891385"
-},
-{
- "id": "pmid:12758065",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/12758065",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:12758065']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12700167"
},
{
- "id": "pmid:11313753",
+ "id": "pmid:11979062",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/11313753",
- "title": "Different types of repeat expansion in the TATA-binding protein gene are associated with a new form of inherited ataxia.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11979062",
+ "title": "Association for serotonin transporter gene variable number tandem repeat polymorphism and schizophrenic disorders.",
"type": "article-journal",
- "doi": "10.1038/sj.ejhg.5200617",
+ "doi": "10.1159/000054952",
"authors": [
- ["C", "Z\u00fchlke"],
- ["Y", "Hellenbroich"],
- ["A", "Dalski"],
- ["N", "Kononowa"],
- ["J", "Hagenah"],
- ["P", "Vieregge"],
- ["O", "Riess"],
- ["C", "Klein"],
- ["E", "Schwinger"]
+ ["Shih-Jen", "Tsai"],
+ ["Wen-Chen", "Ouyang"],
+ ["Chen-Jee", "Hong"]
],
- "publisher": "European journal of human genetics : EJHG",
- "issn": "1018-4813",
- "date": "2001-03-01",
- "abstract": "A novel neurological syndrome has recently been described to be associated with an expanded polyglutamine domain. The expansion results from partial duplication within the TATA-binding protein (TBP). By investigation of 604 sporadic and familial cases with various forms of neurological syndromes and 157 unaffected individuals, we found repeat expansions in the TBP in four patients of two families with autosomal dominant inheritance of ataxia, dystonia, and intellectual decline. Two different genotypes for the repetitive sequence could be demonstrated which led to elongated polyglutamine stretches between 50 and 55 residues, whereas normal alleles with 27 to a maximum of 44 glutamine residues were found in this study. The expansion to 50 or more glutamine residues results in a pathological phenotype and confirms the report of a new polyglutamine disease.",
+ "publisher": "Neuropsychobiology",
+ "issn": "0302-282X",
+ "date": "2002-01-01",
+ "abstract": "In contrast with two previous western reports, a recent study on a Chinese population found an association for allele 12 of the variable number tandem repeat (VNTR) in the second intron of the serotonin transporter (5-HTT) gene and schizophrenic disorders. We have replicated this finding for a Chinese population in Taiwan (114 schizophrenic patients and 127 controls), demonstrating a modest but significant statistical association for the 5-HTT-VNTR allele 12 and schizophrenic patients (one-sided p = 0.043). This positive finding further supports the proposition that the 5-HTT-VNTR allele 12 is a risk factor for schizophrenic disorders in Chinese populations, although the effect is weak.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11313753"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11979062"
},
{
- "id": "pmid:9399691",
+ "id": "pmid:11552131",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/9399691",
- "title": "No evidence for expanded polyglutamine sequences in bipolar disorder and schizophrenia.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11552131",
+ "title": "Possible association of temporomandibular joint pain and dysfunction with a polymorphism in the serotonin transporter gene.",
"type": "article-journal",
- "doi": "10.1038/sj.mp.4000297",
+ "doi": "10.1067/mod.2001.115307",
"authors": [
- ["A L", "Jones"],
- ["F", "Middle"],
- ["C", "Guy"],
- ["G", "Spurlock"],
- ["N J", "Cairns"],
- ["P", "McGuffin"],
- ["N", "Craddock"],
- ["M", "Owen"],
- ["M C", "O'Donovan"]
+ ["H", "Herken"],
+ ["E", "Erdal"],
+ ["N", "Mutlu"],
+ ["", "Barlas O"],
+ ["O", "Cataloluk"],
+ ["F", "Oz"],
+ ["E", "G\u00fcray"]
],
- "publisher": "Molecular psychiatry",
- "issn": "1359-4184",
- "date": "1997-01-01",
- "abstract": "Several recent studies have suggested that expanded CAG repeats may contribute to the genetic transmission of bipolar disorder and schizophrenia. In all known disorders associated with expanded CAG repeats, the repeat sequence is translated into glutamine. Therefore the simplest hypothesis is that one or more proteins with expanded polyglutamine sequences are involved in the pathogenesis of bipolar disorder and schizophrenia. In order to examine this hypothesis, we have used an antibody against expanded polyglutamine sequences to examine Western blots prepared from lymphoblastoid cell lines of patients with schizophrenia and bipolar disorder. We also examined Western blots prepared from left frontal cortex tissue samples obtained from 11 schizophrenics post mortem. With the exception of the TATA-binding protein (TBP), we did not detect any proteins containing expanded polyglutamine sequences. Our data therefore suggest either that the expanded repeats which are associated with these disorders do not encode polyglutamine, or that they are within genes that are not expressed within the tissues investigated here.",
+ "publisher": "American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics",
+ "issn": "0889-5406",
+ "date": "2001-09-01",
+ "abstract": "The purpose of this study was to evaluate the relationship between temporomandibular joint pain and dysfunction and serotonin transporter (5-HTT) gene polymorphism. Forty-eight patients with temporomandibular joint pain and 111 healthy control subjects were examined. The results for the patients and control subjects were not significantly different (P >.05). The analysis of genotype distribution (homozygous for STin 2.10 genotypes of the variable-number tandem-repeat polymorphism) showed significant differences between the patients and control subjects (P =.003). ST 2.10 allele was more frequent in the patients with temporomandibular joint pain and dysfunction. In the control group, however, STin 2.12/12 genotype was significantly higher (P =.017). In the patients who were homozygous or heterozygous for variable-number tandem-repeat variants of 5-HTT STin 2.12 copies, the average scores of somatization and anger were significantly higher than those who were homozygous for STin 2.10 variant (P <.05). The patients who were homozygous for STin 2.10 genotype were also homozygous for \"L\" genotype (P =.019). However, this was not the condition in the control subjects. This study does not provide evidence to support the involvement of 5-HTT gene-linked polymorphic region in temporomandibular joint pain and dysfunction. Our findings indicated that only the presence of the homozygous STin 2.10 genotype of variable-number tandem-repeat is likely to play a substantial role in the genetic predisposition to temporomandibular joint pain and dysfunction and that the STin 2.12/12 genotype may have a protective role against temporomandibular joint pain and dysfunction.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9399691"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11552131"
},
{
- "id": "pmid:8886170",
+ "id": "pmid:22034471",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/8886170",
- "title": "Analysis of polyglutamine-coding repeats in the TATA-binding protein in different human populations and in patients with schizophrenia and bipolar affective disorder.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/22034471",
+ "title": "Huntington's disease: from gene to potential therapy.",
"type": "article-journal",
- "doi": "10.1002/(sici)1096-8628(19960920)67:5<495::aid-ajmg12>3.0.co;2-i",
+ "doi": "10.31887/dcns.2001.3.1/hlehrach",
"authors": [
- ["D C", "Rubinsztein"],
- ["J", "Leggo"],
- ["T J", "Crow"],
- ["L E", "DeLisi"],
- ["C", "Walsh"],
- ["S", "Jain"],
- ["E S", "Paykel"]
+ ["H", "Lehrach"],
+ ["E E", "Wanker"]
],
- "publisher": "American journal of medical genetics",
- "issn": "0148-7299",
- "date": "1996-09-20",
- "abstract": "A new class of disease (including Huntington disease, Kennedy disease, and spinocerebellar ataxias types 1 and 3) results from abnormal expansions of CAG trinucleotides in the coding regions of genes. In all of these diseases the CAG repeats are thought to be translated into polyglutamine tracts. There is accumulating evidence arguing for CAG trinucleotide expansions as one of the causative disease mutations in schizophrenia and bipolar affective disorder. We and others believe that the TATA-binding protein (TBP) is an important candidate to investigate in these diseases as it contains a highly polymorphic stretch of glutamine codons, which are close to the threshold length where the polyglutamine tracts start to be associated with disease. Thus, we examined the lengths of this polyglutamine repeat in normal unrelated East Anglians, South African Blacks, sub-Saharan Africans mainly from Nigeria, and Asian Indians. We also examined 43 bipolar affective disorder patients and 65 schizophrenic patients. The range of polyglutamine tractlengths that we found in humans was from 26-42 codons. No patients with bipolar affective disorder and schizophrenia had abnormal expansions at this locus.",
+ "publisher": "Dialogues in clinical neuroscience",
+ "issn": "1294-8322",
+ "date": "2001-03-01",
+ "abstract": "Huntington's disease (HD) is a progressive, late-onset neurodegenerative illness with autosomal dominant inheritance that affects one in 10 000 individuals in Western Europe. The disease is caused by a polyglutamine repeat expansion located in the N-terminal region of the huntingtin protein. The mutation is likely to act by a gain of function, but the molecular mechanisms by which it leads to neuronal dysfunction and cell death are not yet known. The normal function of huntingtin in cell metabolism is also unclear. There is no therapy for HD. Research on HD should help elucidate the pathogenetic mechanism of this illness in order to develop successful treatments to prevent or slow down symptoms. This article presents new results in HD research focusing on in vivo and in vitro model systems, potential molecular mechanisms of HD, and the development of therapeutic strategies.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8886170"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22034471"
},
{
- "id": "pmid:16141220",
+ "id": "pmid:10794362",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/16141220",
- "title": "Timed mutation and cell-fate mapping reveal reiterated roles of Tbx1 during embryogenesis, and a crucial function during segmentation of the pharyngeal system via regulation of endoderm expansion.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/10794362",
+ "title": "Null alleles at the Huntington disease locus: implications for diagnostics and CAG repeat instability.",
"type": "article-journal",
- "doi": "10.1242/dev.02018",
+ "doi": "10.1089/109065700316480",
"authors": [
- ["Huansheng", "Xu"],
- ["Fabiana", "Cerrato"],
- ["Antonio", "Baldini"]
+ ["L C", "Williams"],
+ ["M R", "Hegde"],
+ ["R", "Nagappan"],
+ ["R L", "Faull"],
+ ["J", "Giles"],
+ ["I", "Winship"],
+ ["K", "Snow"],
+ ["D R", "Love"]
],
- "publisher": "Development (Cambridge, England)",
- "issn": "0950-1991",
- "date": "2005-09-01",
- "abstract": "The definition of time-specific requirements for a developmental gene can pinpoint the processes within which the gene is involved and can reveal potential late functions in structures and organs that fail to develop in germline mutants. Here, we show the first systematic time-course deletion, in parallel with timed cell fate mapping, of a developmentally crucial gene, Tbx1, during mouse embryogenesis. Tbx1 mouse mutants model DiGeorge syndrome, a disorder of pharyngeal and cardiovascular development. Results revealed different time requirements for the development of individual structures, as well as multiple and time-distinct roles during the development of the same organ or system. We also show that Tbx1 is required throughout pharyngeal segmentation for the regulation of endoderm expansion, thus this is the first gene implicated directly in this process. A genetic-based blueprint of crucial developmental times for organs and systems should be a valuable asset for our understanding of birth defect pathogenesis.",
+ "publisher": "Genetic testing",
+ "issn": "1090-6576",
+ "date": "2000-01-01",
+ "abstract": "PCR amplification of the CAG repeat in exon 1 of the IT15 gene is routinely undertaken to confirm a clinical diagnosis of Huntington disease (HD) and to provide predictive testing for at-risk relatives of affected individuals. Our studies have detected null alleles on the chromosome carrying the expanded repeat in three of 91 apparently unrelated HD families. Sequence analysis of these alleles has revealed the same mutation event, leading to the juxtaposition of uninterrupted CAG and CCG repeats. These data suggest that a mutation-prone region exists in the IT15 gene bounded by the CAG and CCG repeats and that caution should be exercised in designing primers that anneal to the region bounded by these repeats. Two of the HD families segregated null alleles with expanded uninterrupted CAG repeats at the lower end of the zone of reduced penetrance. The expanded repeats are meiotically unstable in these families, although this instability is within a small range of repeat lengths. The haplotypes of the disease-causing chromosomes in these two families differ, only one of which is similar to that reported previously as being specific for new HD mutations. Finally, no apparent mitotic instability of the uninterrupted CAG repeat was observed in the brain of one of the HD individuals.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16141220"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10794362"
},
{
- "id": "pmid:10440825",
+ "id": "pmid:10441201",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/10440825",
- "title": "Patient with a 22q11.2 deletion with no overlap of the minimal DiGeorge syndrome critical region (MDGCR).",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/10441201",
+ "title": "Comparative semi-automated analysis of (CAG) repeats in the Huntington disease gene: use of internal standards.",
"type": "article-journal",
- "doi": "",
+ "doi": "10.1006/mcpr.1999.0248",
"authors": [
- ["L", "McQuade"],
- ["J", "Christodoulou"],
- ["M", "Budarf"],
- ["R", "Sachdev"],
- ["M", "Wilson"],
- ["B", "Emanuel"],
- ["A", "Colley"]
+ ["L C", "Williams"],
+ ["M R", "Hegde"],
+ ["G", "Herrera"],
+ ["P M", "Stapleton"],
+ ["D R", "Love"]
],
- "publisher": "American journal of medical genetics",
- "issn": "0148-7299",
- "date": "1999-09-03",
- "abstract": "The apparent lack of genotype/phenotype correlation in patients with the DiGeorge anomaly and velocardiofacial syndrome (DGA/VCFS; the \"22q11 deletion syndrome\") indicates a complex genetic condition. Most cases, whatever the phenotype, have a 1.5-3 Mb chromosomal deletion that includes the minimal DiGeorge critical region (MDGCR). Another potential critical region on 22q11 has been suggested based on two patients with distal deletions outside the MDGCR. We report on a patient with a VCFS phenotype who has a deletion, mapped by short tandem repeat polymorphic loci and fluorescence in situ hybridization analysis, distal to and not overlapping the MDGCR. This patient is deleted for several genes, including the T-box 1 gene (TBX1; a transcription regulator expressed early in embryogenesis) and catechol-O-methyltransferase (COMT; involved in neurotransmitter metabolism). We discuss the role these two genes may play in the clinical phenotype of the patient.",
+ "publisher": "Molecular and cellular probes",
+ "issn": "0890-8508",
+ "date": "1999-08-01",
+ "abstract": "Huntington disease (HD) belongs to the group of neurodegenerative disorders characterized by unstable expanded trinucleotide repeats. In the case of HD, the expansion of a CAG repeat occurs in the IT15 gene. The detection of the expanded CAG repeats has usually involved the electrophoretic separation of polymerase chain reaction (PCR) amplification products using conventional agarose and acrylamide gel electrophoresis. We have undertaken the comparative analysis of sizing CAG repeats of the IT15 gene using radioactive and fluorescent PCR amplification, and the subsequent separation of these products by slab gel and capillary electrophoresis. The assays have been performed on both cloned and sequenced CAG repeats, as well as genomic DNA from HD patients with a wide range of repeat lengths. The mobility of the CAG repeat amplification products of the IT15 gene is greater using capillary electrophoresis compared to slab gel electrophoresis. The analysis of 40 DNA samples from HD patients indicates that the mobility difference increases with the length of the repeat. However, we have devised an allele ladder for sizing the CAG repeats. This ladder provides a mandatory internal calibration system for diagnostic purposes and enables the confident use of either capillary or slab gel electrophoresis for sizing HD alleles.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10440825"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10441201"
},
{
- "id": "pmid:40720054",
+ "id": "pmid:10091627",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/40720054",
- "title": "Long-Range PCR and Nanopore Sequencing Enables High-Throughput Detection of TCF4 Trinucleotide Repeat Expansions in Fuchs Endothelial Corneal Dystrophy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/10091627",
+ "title": "Differential clinical and motor control function in a pair of monozygotic twins with Huntington's disease.",
"type": "article-journal",
- "doi": "10.1007/s40291-025-00803-8",
+ "doi": "10.1002/1531-8257(199903)14:2<320::aid-mds1018>3.0.co;2-z",
"authors": [
- ["Bushra", "Alayed"],
- ["Salina", "Siddiqui"],
- ["Seema", "Anand"],
- ["Chris F", "Inglehearn"],
- ["Christopher M", "Watson"],
- ["Manir", "Ali"]
+ ["N", "Georgiou"],
+ ["J L", "Bradshaw"],
+ ["E", "Chiu"],
+ ["A", "Tudor"],
+ ["L", "O'Gorman"],
+ ["J G", "Phillips"]
],
- "publisher": "Molecular diagnosis & therapy",
- "issn": "1179-2000",
- "date": "2025-07-28",
- "abstract": "Trinucleotide repeat expansion in CTG18.1, in intron 2 of TCF4 (MIM *602272, #613267), is the main cause of Fuchs endothelial corneal dystrophy (FECD), accounting for around 75% of cases in Caucasians. CTG18.1 repeat expansion has typically been detected in peripheral blood genomic DNA by Southern blotting or short tandem repeat polymerase chain reaction (STR-PCR) combined with triplet-repeat primed PCR (TP-PCR) if needed. However both methods estimate the size of the expanded repeat relative to a size standard, and the former requires microgram amounts of DNA. To support the development of therapies, a high-throughput screening approach for repeat expansions in FECD is required. Here, we present a sensitive assay using long-range PCR and nanopore sequencing of genomic DNA to accurately resolve the CTG18.1 repeat.",
+ "publisher": "Movement disorders : official journal of the Movement Disorder Society",
+ "issn": "0885-3185",
+ "date": "1999-03-01",
+ "abstract": "We report a pair of monozygotic Huntington's disease (HD) twins who, although sharing identical CAG repeat lengths, not only present with marked differences in clinical symptoms but also behavioral abilities as measured by our experimental procedures. Both HD twins and two healthy control subjects were tested twice over 2 years. Patient A was generally more impaired at a motor level, whereas Patient B showed greater attentional impairment; Patient B, however, showed more progressive deterioration. The control subjects' performance remained consistent over the 2-year interval. Patient A clinically had the more hyperkinetic hypotonic variant of the disease, whereas Patient B, who was the more impaired, presented with a more hypokinetic hypertonic (rigid) variant. The influences of epigenetic pre- and postnatal environmental factors should not be ignored.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40720054"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10091627"
},
{
- "id": "pmid:39288343",
+ "id": "pmid:9626775",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/39288343",
- "title": "Change in Visual Acuity of Patients With Fuchs Endothelial Corneal Dystrophy Over 1 Year.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9626775",
+ "title": "Severity of cognitive impairment in juvenile and late-onset Huntington disease.",
"type": "article-journal",
- "doi": "10.1097/ico.0000000000003590",
+ "doi": "10.1001/archneur.55.6.835",
"authors": [
- ["Oliver", "Dorado-Cortez"],
- ["Emmanuel", "Crouzet"],
- ["Marie Caroline", "Trone"],
- ["Philippe", "Gain"],
- ["Zhiguo", "He"],
- ["Hanielle", "Vaitinadapoule"],
- ["Marielle", "Mentek"],
- ["Fr\u00e9d\u00e9ric", "Mascarelli"],
- ["Sylvain", "Poinard"],
- ["Mari", "Yasunaga"],
- ["Go", "Nishiuchi"],
- ["Noriko", "Koizumi"],
- ["Naoki", "Okumura"],
- ["Gilles", "Thuret"]
+ ["E", "G\u00f3mez-Tortosa"],
+ ["A", "del Barrio"],
+ ["P J", "Garc\u00eda Ruiz"],
+ ["R S", "Pernaute"],
+ ["J", "Ben\u00edtez"],
+ ["A", "Barroso"],
+ ["F J", "Jim\u00e9nez"],
+ ["J", "Garc\u00eda Y\u00e9benes"]
],
- "publisher": "Cornea",
- "issn": "1536-4798",
- "date": "2024-07-09",
- "abstract": "To determine whether the clinical and paraclinical course of Fuchs endothelial corneal dystrophy (FECD) over 1 year is related to the extent of triplet repetition in the transcription factor 4 (TCF4) gene.",
+ "publisher": "Archives of neurology",
+ "issn": "0003-9942",
+ "date": "1998-06-01",
+ "abstract": "To compare the severity of cognitive impairment among groups of patients with different age ranges at the onset of Huntington disease (HD) and to evaluate the variable influence of motor and cognitive deficits on functional disability across different ages at the onset of HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39288343"
-},
-{
- "id": "pmid:39278108",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/39278108",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:39278108']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9626775"
},
{
- "id": "pmid:37204786",
+ "id": "pmid:9339688",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/37204786",
- "title": "The TCF4 Trinucleotide Repeat Expansion of Fuchs' Endothelial Corneal Dystrophy: Implications for the Anterior Segment of the Eye.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9339688",
+ "title": "Genetic testing of children at risk for Huntington's disease. US Huntington Disease Genetic Testing Group.",
"type": "article-journal",
- "doi": "10.1167/iovs.64.5.16",
+ "doi": "10.1212/wnl.49.4.1048",
"authors": [
- ["Jiaxin", "Hu"],
- ["Xin", "Gong"],
- ["Samantha T", "Johnson"],
- ["David R", "Corey"],
- ["V Vinod", "Mootha"]
+ ["M A", "Nance"]
],
- "publisher": "Investigative ophthalmology & visual science",
- "issn": "1552-5783",
- "date": "2023-05-01",
- "abstract": "In the United States, 70% of Fuchs' endothelial corneal dystrophy (FECD) cases are caused by an intronic trinucleotide repeat expansion in the TCF4 gene. CUG repeat RNA transcripts from this expansion accumulate as nuclear foci in the corneal endothelium. In this study, we sought to detect foci in other anterior segment cell types and assess their molecular impact.",
+ "publisher": "Neurology",
+ "issn": "0028-3878",
+ "date": "1997-10-01",
+ "abstract": "We reviewed 44 symptomatic children tested for CAG repeat expansions in the gene responsible for Huntington's disease (HD). Thirty-three patients had CAG repeat expansions, and 11 did not. No patient with a CAG repeat expansion had a negative family history of HD. Of the 15 patients presenting in the first decade, 12 had greater than 80 CAG repeats and a clinical profile at the time of the test that included two or more of the following: declining school performance, seizures, oral motor dysfunction, rigidity, and gait disorder. Three patients with smaller CAG repeat expansions had incomplete or atypical symptom profiles. Symptom patterns in patients presenting in the second decade were more varied but usually included behavioral and motor symptoms. Patients without CAG expansions had incomplete or atypical symptom profiles. We define the historical and clinical profiles of HD presenting in the first two decades and suggest that physicians exercise restraint in using a \"diagnostic\" gene test for HD in the evaluation of at-risk children with incomplete or atypical symptom profiles or no family history of HD, in whom test results are very likely to be normal or unrelated to the patient's symptoms.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37204786"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9339688"
},
{
- "id": "pmid:37169279",
+ "id": "pmid:8931689",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/37169279",
- "title": "Dysregulation of DNA repair genes in Fuchs endothelial corneal dystrophy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/8931689",
+ "title": "Transglutaminase activity is related to CAG repeat length in patients with Huntington's disease.",
"type": "article-journal",
- "doi": "10.1016/j.exer.2023.109499",
+ "doi": "10.1007/s004390050273",
"authors": [
- ["Shazia", "Ashraf"],
- ["Neha", "Deshpande"],
- ["Shivakumar", "Vasanth"],
- ["Geetha", "Melangath"],
- ["Raymond J", "Wong"],
- ["Yan", "Zhao"],
- ["Marianne O", "Price"],
- ["Francis W", "Price"],
- ["Ula V", "Jurkunas"]
+ ["L", "Cariello"],
+ ["T", "de Cristofaro"],
+ ["L", "Zanetti"],
+ ["T", "Cuomo"],
+ ["L", "Di Maio"],
+ ["G", "Campanella"],
+ ["S", "Rinaldi"],
+ ["P", "Zanetti"],
+ ["R", "Di Lauro"],
+ ["S", "Varrone"]
],
- "publisher": "Experimental eye research",
- "issn": "1096-0007",
- "date": "2023-05-09",
- "abstract": "Fuchs Endothelial Corneal Dystrophy (FECD), a late-onset oxidative stress disorder, is the most common cause of corneal endothelial degeneration and is genetically associated with CTG repeat expansion in Transcription Factor 4 (TCF4). We previously reported accumulation of nuclear (nDNA) and mitochondrial (mtDNA) damage in FECD. Specifically, mtDNA damage was a prominent finding in development of disease in the ultraviolet-A (UVA) induced FECD mouse model. We hypothesize that an aberrant DNA repair may contribute to the increased DNA damage seen in FECD. We analyzed differential expression profiles of 84 DNA repair genes by real-time PCR arrays using Human DNA Repair RT-Profiler plates using cDNA extracted from Descemet's membrane-corneal endothelium (DM-CE) obtained from FECD patients with expanded (>40) or non-expanded (<40) intronic CTG repeats in TCF4 gene and from age-matched normal donors. Change in mRNA expression of <0.5- or >2.0-fold in FECD relative to normal was set as cutoff for down- or upregulation. Downregulated mitochondrial genes were further validated using the UVA-based mouse model of FECD. FECD specimens exhibited downregulation of 9 genes and upregulation of 8 genes belonging to the four major DNA repair pathways, namely, base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), and double strand break (DSB) repair, compared to normal donors. MMR gene MSH2 and BER gene POLB were preferentially upregulated in expanded FECD. BER genes LIG3 and NEIL2, DSB repair genes PARP3 and TOP3A, NER gene XPC, and unclassified pathway gene TREX1, were downregulated in both expanded and non-expanded FECD. MtDNA repair genes, Lig3, Neil2, and Top3a, were also downregulated in the UVA-based mouse model of FECD. Our findings identify impaired DNA repair pathways that may play an important role in DNA damage due to oxidative stress as well as genetic predisposition noted in FECD.",
+ "publisher": "Human genetics",
+ "issn": "0340-6717",
+ "date": "1996-12-01",
+ "abstract": "Huntington's disease (HD) is a neurodegenerative disorder associated with CAG repeat expansion. We measured transglutaminase (TGase) activity in lymphocytes from 35 HD patients and from healthy individuals to ascertain whether it was altered in this condition. TGase activity was above maximum control levels in 25% of HD patients; it was correlated with the age of the patient and inversely correlated with the CAG repeat length. These results suggest that: (1) HD could be biochemically heterogeneous, and (2) the length of the CAG repeat expansion/TGase ratio could be important in the manifestation of HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37169279"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8931689"
},
{
- "id": "pmid:34946867",
+ "id": "pmid:8572659",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/34946867",
- "title": "Should Patients with Kearns-Sayre Syndrome and Corneal Endothelial Failure Be Genotyped for a",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/8572659",
+ "title": "Relationship between trinucleotide repeats and neuropathological changes in Huntington's disease.",
"type": "article-journal",
- "doi": "10.3390/genes12121918",
+ "doi": "10.1002/ana.410390120",
"authors": [
- ["Lubica", "Dudakova"],
- ["Pavlina", "Skalicka"],
- ["Alice E", "Davidson"],
- ["Amanda N", "Sadan"],
- ["Monika", "Chylova"],
- ["Helena", "Jahnova"],
- ["Nicole", "Anteneova"],
- ["Marketa", "Tesarova"],
- ["Tomas", "Honzik"],
- ["Petra", "Liskova"]
+ ["S", "Furtado"],
+ ["O", "Suchowersky"],
+ ["B", "Rewcastle"],
+ ["L", "Graham"],
+ ["M L", "Klimek"],
+ ["A", "Garber"]
],
- "publisher": "Genes",
- "issn": "2073-4425",
- "date": "2021-11-29",
- "abstract": "The aim of this study was to describe the ocular phenotype in a case with Kearns-Sayre syndrome (KSS) spectrum and to determine if corneal endothelial cell dysfunction could be attributed to other known distinct genetic causes. Herein, genomic DNA was extracted from blood and exome sequencing was performed. Non-coding gene regions implicated in corneal endothelial dystrophies were screened by Sanger sequencing. In addition, a repeat expansion situated within an intron of",
+ "publisher": "Annals of neurology",
+ "issn": "0364-5134",
+ "date": "1996-01-01",
+ "abstract": "The discovery of the Huntington's disease (HD) gene has provided the impetus to determine the association between the triplet repeat sequences and clinical manifestations of the disease. The present study is directed toward determining the relationship between the triplet repeat sequences and severity of the neurodegenerative process. Nineteen HD postmortem cases were evaluated for neuropathological changes as well as for the number of trinucleotide repeat sequences, each in a blinded fashion. Each case was assigned a gross grade according to the scale of Vonsattel and colleagues (1985); neuronal counts were then performed on both the caudate and the putamen. For 7 of the postmortem cases, blood had been collected prior to death and was analyzed for the HD gene. For the 12 remaining cases for which blood was unavailable, DNA from the frontal neocortex and striatum was extracted from frozen or formalin-fixed paraffinized tissue and subsequently analyzed for the HD gene. When correlation was made for age at death, greater numbers of trinucleotide repeats were associated with greater neuronal loss, in both the caudate (r = 0.9641, p < 0.001) and the putamen (r = 0.9652, p < 0.001). When correction was made for disease duration, the correlation was again significant, for both the caudate (r = 0.6396, p < 0.01) and the putamen (r = 0.6710, p < 0.001). This suggests that in HD, longer trinucleotide repeat length is associated with a faster rate of deterioration and greater pathological severity. A comparison of trinucleotide repeat length in different brain regions in 4 of the HD postmortem cases associated with greater numbers of repeats consistently demonstrated fewer repeats in the cerebellum than in the frontal cortex, striatum or blood.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34946867"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8572659"
},
{
- "id": "pmid:34855896",
+ "id": "pmid:7868117",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/34855896",
- "title": "Comparison of TCF4 repeat expansion length in corneal endothelium and leukocytes of patients with Fuchs endothelial corneal dystrophy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/7868117",
+ "title": "Somatic expansion of the (CAG)n repeat in Huntington disease brains.",
"type": "article-journal",
- "doi": "10.1371/journal.pone.0260837",
+ "doi": "10.1007/bf00225192",
"authors": [
- ["Eric D", "Wieben"],
- ["Ross A", "Aleff"],
- ["Tommy A", "Rinkoski"],
- ["Keith H", "Baratz"],
- ["Shubham", "Basu"],
- ["Sanjay V", "Patel"],
- ["Leo J", "Maguire"],
- ["Michael P", "Fautsch"]
+ ["K E", "De Rooij"],
+ ["P A", "De Koning Gans"],
+ ["R A", "Roos"],
+ ["G J", "Van Ommen"],
+ ["J T", "Den Dunnen"]
],
- "publisher": "PloS one",
- "issn": "1932-6203",
- "date": "2021-12-02",
- "abstract": "Expansion of CTG trinucleotide repeats (TNR) in the transcription factor 4 (TCF4) gene is highly associated with Fuchs Endothelial Corneal Dystrophy (FECD). Due to limitations in the availability of DNA from diseased corneal endothelium, sizing of CTG repeats in FECD patients has typically been determined using DNA samples isolated from peripheral blood leukocytes. However, it is non-feasible to extract enough DNA from surgically isolated FECD corneal endothelial tissue to determine repeat length based on current technology. To circumvent this issue, total RNA was isolated from FECD corneal endothelium and sequenced using long-read sequencing. Southern blotting of DNA samples isolated from primary cultures of corneal endothelium from these same affected individuals was also assessed. Both long read sequencing and Southern blot analysis showed significantly longer CTG TNR expansion (>1000 repeats) in the corneal endothelium from FECD patients than those characterized in leukocytes from the same individuals (<90 repeats). Our findings suggest that the TCF4 CTG repeat expansions in the FECD corneal endothelium are much longer than those found in leukocytes.",
+ "publisher": "Human genetics",
+ "issn": "0340-6717",
+ "date": "1995-03-01",
+ "abstract": "The mutation causing Huntington disease (HD) has been identified as an expansion of a polymorphic (CAG)n repeat in the 5' part of the huntingtin gene. The specific neuropathology of HD, viz. selective neuronal loss in the caudate nucleus and putamen, cannot be explained by the widespread expression of the gene. Since somatic expansion is observed in affected tissue in myotonic dystrophy, we have studied the length of the (CAG)n repeat in various regions of the brain. Although we have not found clear differences when comparing severely and mildly affected regions, we have observed a minor increase in repeat length upon comparison of affected brain samples with cerebellum or peripheral blood. Hence, although further somatic amplification seems to occur in affected areas of the brain, the differences between affected and unaffected regions are too small to make this mechanism an obvious candidate for the cause of differential neuronal degeneration in HD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34855896"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7868117"
},
{
- "id": "pmid:32934897",
+ "id": "pmid:8162053",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/32934897",
- "title": "Trinucleotide Repeat-Targeting dCas9 as a Therapeutic Strategy for Fuchs' Endothelial Corneal Dystrophy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/8162053",
+ "title": "A CCG repeat polymorphism adjacent to the CAG repeat in the Huntington disease gene: implications for diagnostic accuracy and predictive testing.",
"type": "article-journal",
- "doi": "10.1167/tvst.9.9.47",
+ "doi": "10.1093/hmg/3.1.65",
"authors": [
- ["Ziye", "Rong"],
- ["Xin", "Gong"],
- ["John D", "Hulleman"],
- ["David R", "Corey"],
- ["V Vinod", "Mootha"]
+ ["S E", "Andrew"],
+ ["Y P", "Goldberg"],
+ ["J", "Theilmann"],
+ ["J", "Zeisler"],
+ ["M R", "Hayden"]
],
- "publisher": "Translational vision science & technology",
- "issn": "2164-2591",
- "date": "2020-08-31",
- "abstract": "Fuchs' endothelial corneal dystrophy (FECD) is the leading indication for corneal transplantation. Seventy percent of cases are caused by an intronic CTG triplet repeat expansion in the",
+ "publisher": "Human molecular genetics",
+ "issn": "0964-6906",
+ "date": "1994-01-01",
+ "abstract": "The polymorphic CAG repeat that is expanded on Huntington disease (HD) chromosomes is flanked by a CCG repeat. Here we show that this CCG tract, previously assumed to be invariant at seven CCG repeats, is also polymorphic. We have identified five CCG alleles from 205 normal chromosomes, with 137 (67%) having alleles of seven repeats, five (2%) with nine repeats, 61 (30%) with 10 repeats, one (0.5%) with 11 repeats and one (0.5%) with 12 repeats. In contrast, analysis of 113 HD chromosomes revealed that the majority (105 chromosomes, 93%) contained seven CCG repeats, while the remaining eight chromosomes (7%) had allele sizes of 10 CCG repeats. Despite evidence that both CAG and CCG are polymorphic on normal chromosomes, we have found that it is only the CAG length that has a significant impact on age of onset. The discovery of larger sized CCG alleles, however, has significant implications for the assessment of CAG repeat length, particularly for persons with estimated CAG size of 36-42 repeats, since an overestimation of CAG length in this range could result in erroneous information being imparted to patients.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32934897"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8162053"
},
{
- "id": "pmid:32639312",
+ "id": "pmid:8401589",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/32639312",
- "title": "Lower Corneal Haze and Aberrations in Descemet Membrane Endothelial Keratoplasty Versus Descemet Stripping Automated Endothelial Keratoplasty in Fellow Eyes for Fuchs Endothelial Corneal Dystrophy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/8401589",
+ "title": "The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease.",
"type": "article-journal",
- "doi": "10.1097/ico.0000000000002416",
+ "doi": "10.1038/ng0893-398",
"authors": [
- ["William H", "Waldrop"],
- ["Matthew J", "Gillings"],
- ["Danielle M", "Robertson"],
- ["W Matthew", "Petroll"],
- ["V Vinod", "Mootha"]
+ ["S E", "Andrew"],
+ ["Y P", "Goldberg"],
+ ["B", "Kremer"],
+ ["H", "Telenius"],
+ ["J", "Theilmann"],
+ ["S", "Adam"],
+ ["E", "Starr"],
+ ["F", "Squitieri"],
+ ["B", "Lin"],
+ ["M A", "Kalchman"]
],
- "publisher": "Cornea",
- "issn": "1536-4798",
- "date": "2020-10-01",
- "abstract": "To investigate the long-term corneal changes in patients with Fuchs endothelial corneal dystrophy contributing to superior postoperative visual outcomes after Descemet membrane endothelial keratoplasty (DMEK) compared with Descemet stripping automated endothelial keratoplasty (DSAEK).",
+ "publisher": "Nature genetics",
+ "issn": "1061-4036",
+ "date": "1993-08-01",
+ "abstract": "Huntington's disease (HD) is associated with the expansion of a CAG trinucleotide repeat in a novel gene. We have assessed 360 HD individuals from 259 unrelated families and found a highly significant correlation (r = 0.70, p = 10(-7)) between the age of onset and the repeat length, which accounts for approximately 50% of the variation in the age of onset. Significant associations were also found between repeat length and age of death and onset of other clinical features. Sib pair and parent-child analysis revealed that the CAG repeat demonstrates only mild instability. Affected HD siblings had significant correlations for trinucleotide expansion (r = 0.66, p < 0.001) which was not apparent for affected parent-child pairs.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32639312"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:8401589"
},
{
- "id": "pmid:30733599",
+ "id": "pmid:32493488",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/30733599",
- "title": "CRISPR/Cas9-targeted enrichment and long-read sequencing of the Fuchs endothelial corneal dystrophy-associated TCF4 triplet repeat.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/32493488",
+ "title": "Oculopharyngodistal myopathy with coexisting histology of systemic neuronal intranuclear inclusion disease: Clinicopathologic features of an autopsied patient harboring CGG repeat expansions in LRP12.",
"type": "article-journal",
- "doi": "10.1038/s41436-019-0453-x",
+ "doi": "10.1186/s40478-020-00945-2",
"authors": [
- ["Nathaniel J", "Hafford-Tear"],
- ["Yu-Chih", "Tsai"],
- ["Amanda N", "Sadan"],
- ["Beatriz", "Sanchez-Pintado"],
- ["Christina", "Zarouchlioti"],
- ["Geoffrey J", "Maher"],
- ["Petra", "Liskova"],
- ["Stephen J", "Tuft"],
- ["Alison J", "Hardcastle"],
- ["Tyson A", "Clark"],
- ["Alice E", "Davidson"]
+ ["Rie", "Saito"],
+ ["Hiroshi", "Shimizu"],
+ ["Takeshi", "Miura"],
+ ["Norikazu", "Hara"],
+ ["Naomi", "Mezaki"],
+ ["Yo", "Higuchi"],
+ ["Akinori", "Miyashita"],
+ ["Izumi", "Kawachi"],
+ ["Kazuhiro", "Sanpei"],
+ ["Yoshiaki", "Honma"],
+ ["Osamu", "Onodera"],
+ ["Takeshi", "Ikeuchi"],
+ ["Akiyoshi", "Kakita"]
],
- "publisher": "Genetics in medicine : official journal of the American College of Medical Genetics",
- "issn": "1530-0366",
- "date": "2019-02-08",
- "abstract": "To demonstrate the utility of an amplification-free long-read sequencing method to characterize the Fuchs endothelial corneal dystrophy (FECD)-associated intronic TCF4 triplet repeat (CTG18.1).",
+ "publisher": "Acta neuropathologica communications",
+ "issn": "2051-5960",
+ "date": "2020-06-03",
+ "abstract": "",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30733599"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32493488"
},
{
- "id": "pmid:30267097",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/30267097",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:30267097']' timed out after 3 seconds"
-},
-{
- "id": "pmid:29325021",
+ "id": "pmid:34452200",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/29325021",
- "title": "Oligonucleotides targeting TCF4 triplet repeat expansion inhibit RNA foci and mis-splicing in Fuchs' dystrophy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/34452200",
+ "title": "Development, Characterization, and In Vivo Evaluation of a Novel Aptamer (Anti-MUC1/Y) for Breast Cancer Therapy.",
"type": "article-journal",
- "doi": "10.1093/hmg/ddy018",
+ "doi": "10.3390/pharmaceutics13081239",
"authors": [
- ["Jiaxin", "Hu"],
- ["Ziye", "Rong"],
- ["Xin", "Gong"],
- ["Zhengyang", "Zhou"],
- ["Vivek K", "Sharma"],
- ["Chao", "Xing"],
- ["Jonathan K", "Watts"],
- ["David R", "Corey"],
- ["V Vinod", "Mootha"]
+ ["Huma", "Khan"],
+ ["Vaidehi", "Makwana"],
+ ["Sofia Nascimento Dos", "Santos"],
+ ["Carlos Eduardo", "Bonacossa de Almeida"],
+ ["Ralph", "Santos-Oliveira"],
+ ["Sotiris", "Missailidis"]
],
- "publisher": "Human molecular genetics",
- "issn": "1460-2083",
- "date": "2018-03-15",
- "abstract": "Fuchs' endothelial corneal dystrophy (FECD) is the most common repeat expansion disorder. FECD impacts 4% of U.S. population and is the leading indication for corneal transplantation. Most cases are caused by an expanded intronic CUG tract in the TCF4 gene that forms nuclear foci, sequesters splicing factors and impairs splicing. We investigated the sense and antisense RNA landscape at the FECD gene and find that the sense-expanded repeat transcript is the predominant species in patient corneas. In patient tissue, sense foci number were negatively correlated with age and showed no correlation with sex. Each endothelial cell has \u223c2 sense foci and each foci is single RNA molecule. We designed antisense oligonucleotides (ASOs) to target the mutant-repetitive RNA and demonstrated potent inhibition of foci in patient-derived cells. Ex vivo treatment of FECD human corneas effectively inhibits foci and reverses pathological changes in splicing. FECD has the potential to be a model for treating many trinucleotide repeat diseases and targeting the TCF4 expansion with ASOs represents a promising therapeutic strategy to prevent and treat FECD.",
+ "publisher": "Pharmaceutics",
+ "issn": "1999-4923",
+ "date": "2021-08-11",
+ "abstract": "MUC1, the transmembrane glycoprotein Mucin 1, is usually found to be overexpressed in a variety of epithelial cancers playing an important role in disease progression. MUC1 isoforms such as MUC1/Y, which lacks the entire variable number of tandem repeat region, are involved in oncogenic processes by enhancing tumour initiation. MUC1/Y is therefore considered a promising target for the identification and treatment of epithelial cancers; but so far, the precise role of MUC1/Y remains to be elucidated. In this work, we developed and identified a DNA aptamer that specifically recognizes the splice variant MUC1/Y for the first time. The DNA aptamer could bind to a wide variety of human cancer cells, and treatment of MUC1/Y positive cells resulted in reduced growth in vitro. Moreover, MUC1/Y aptamer inhibited the tumour growth of breast cancer cells in vivo. The present study highlights the importance of targeting MUC1/Y for cancer treatment and unravels the suitability of a DNA aptamer to act as a new therapeutic tool.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29325021"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34452200"
},
{
- "id": "pmid:29196769",
+ "id": "pmid:28407289",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/29196769",
- "title": "CTG18.1 Expansion in TCF4 Among African Americans With Fuchs' Corneal Dystrophy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/28407289",
+ "title": "Dual Role of the Extracellular Domain of Human Mucin MUC1 in Metastasis.",
"type": "article-journal",
- "doi": "10.1167/iovs.17-21661",
+ "doi": "10.1002/jcb.26056",
"authors": [
- ["Allen O", "Eghrari"],
- ["Sina", "Vahedi"],
- ["Natalie A", "Afshari"],
- ["S Amer", "Riazuddin"],
- ["John D", "Gottsch"]
+ ["M S", "Syrkina"],
+ ["A A", "Maslakova"],
+ ["D M", "Potashnikova"],
+ ["V P", "Veiko"],
+ ["Y S", "Vassetzky"],
+ ["M A", "Rubtsov"]
],
- "publisher": "Investigative ophthalmology & visual science",
- "issn": "1552-5783",
- "date": "2017-12-01",
- "abstract": "Studies of Fuchs' dystrophy have largely focused on individuals of European origin. Characterization of disease among African Americans is required to ensure prognostic factors and therapeutic approaches are applicable across diverse patient populations.",
+ "publisher": "Journal of cellular biochemistry",
+ "issn": "1097-4644",
+ "date": "2017-06-09",
+ "abstract": "Human mucin MUC1 plays an important role in cancer development. The increased level of this molecule expression during cancer cell progression induces metastasis and is associated with poor prognosis for patients. There is a large body of experimental data on the role of various functional domains of human mucin MUC1 in metastasis. While, the cytoplasmic domain determined to play a definitive role, the influence of extracellular domain on cancer cell invasiveness still remains unclear. The present paper reveals that the extracellular domain of MUC1 molecule consists of two functional subdomains-the region of tandem repeats (TR) and the region of irregular repeats (IR). We demonstrate the ability of each of these subdomains to alter the invasiveness of cancer cells. The presence of the MUC1 molecules containing TR subdomain (MUC1-TR) on the surface of low-invasive cancer cells leads to the increase in their transendothelial migration potency, while the addition of the IR subdomain to the MUC1-TR molecule (MUC1-IR-TR) restores their natural low invasiveness. J. Cell. Biochem. 118: 4002-4011, 2017. \u00a9 2017 Wiley Periodicals, Inc.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29196769"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28407289"
},
{
- "id": "pmid:26401622",
+ "id": "pmid:23778023",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26401622",
- "title": "Correlation of Severity of Fuchs Endothelial Corneal Dystrophy With Triplet Repeat Expansion in TCF4.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23778023",
+ "title": "Serum KL-6 concentrations are associated with molecular sizes and efflux behavior of KL-6/MUC1 in healthy subjects.",
"type": "article-journal",
- "doi": "10.1001/jamaophthalmol.2015.3430",
+ "doi": "10.1016/j.cca.2013.06.002",
"authors": [
- ["Ahmed Z", "Soliman"],
- ["Chao", "Xing"],
- ["Salma H", "Radwan"],
- ["Xin", "Gong"],
- ["V Vinod", "Mootha"]
+ ["Masahiko", "Shigemura"],
+ ["Satoshi", "Konno"],
+ ["Yasuyuki", "Nasuhara"],
+ ["Noriharu", "Shijubo"],
+ ["Chikara", "Shimizu"],
+ ["Masaharu", "Nishimura"]
],
- "publisher": "JAMA ophthalmology",
- "issn": "2168-6173",
- "date": "2015-12-01",
- "abstract": "The CTG18.1 triplet repeat expansion in TCF4 has recently been found to be a common functional variant contributing significant risk to the development of Fuchs endothelial corneal dystrophy (FECD) in Eurasian populations.",
+ "publisher": "Clinica chimica acta; international journal of clinical chemistry",
+ "issn": "1873-3492",
+ "date": "2013-06-15",
+ "abstract": "Serum KL-6, a sialylated sugar chain on human MUC1, is used as a marker of interstitial lung diseases. We recently reported that efflux behavior of KL-6/MUC1 from the alveoli into the bloodstream assessed by molecular analysis differed according to genetically determined molecular sizes and influenced serum KL-6 concentrations in sarcoidosis. This study was designed to investigate associations between molecular size and efflux behavior of KL-6/MUC1, and factors contributing to serum KL-6 concentrations in healthy subjects.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26401622"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23778023"
},
{
- "id": "pmid:26218914",
+ "id": "pmid:19625949",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26218914",
- "title": "Trinucleotide Repeat Expansion in the TCF4 Gene in Fuchs' Endothelial Corneal Dystrophy in Japanese.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19625949",
+ "title": "Comparative immunohistochemical study of MUC1 and carbohydrate antigens in breast benign disease and normal mammary gland.",
"type": "article-journal",
- "doi": "10.1167/iovs.15-17082",
+ "doi": "10.1097/pai.0b013e3181ac1c20",
"authors": [
- ["Masakazu", "Nakano"],
- ["Naoki", "Okumura"],
- ["Hiroko", "Nakagawa"],
- ["Noriko", "Koizumi"],
- ["Yoko", "Ikeda"],
- ["Morio", "Ueno"],
- ["Kengo", "Yoshii"],
- ["Hiroko", "Adachi"],
- ["Ross A", "Aleff"],
- ["Malinda L", "Butz"],
- ["W Edward", "Highsmith"],
- ["Kei", "Tashiro"],
- ["Eric D", "Wieben"],
- ["Shigeru", "Kinoshita"],
- ["Keith H", "Baratz"]
+ ["Sandra O", "Demichelis"],
+ ["Cecilio G", "Alberdi"],
+ ["Walter J", "Servi"],
+ ["Marina T", "Isla-Larrain"],
+ ["Amada", "Segal-Eiras"],
+ ["Mar\u00eda Virginia", "Croce"]
],
- "publisher": "Investigative ophthalmology & visual science",
- "issn": "1552-5783",
- "date": "2015-07-01",
- "abstract": "The purpose of this study was to evaluate the association between the intronic expansion of a trinucleotide repeat (TNR) in the TCF4 gene and Fuchs' endothelial corneal dystrophy (FECD) in a Japanese population.",
+ "publisher": "Applied immunohistochemistry & molecular morphology : AIMM",
+ "issn": "1533-4058",
+ "date": "2010-01-01",
+ "abstract": "The aim was to compare the expression of MUC1 and carbohydrate antigens in 124 tissue samples; 42 fibroadenoma (FA), 23 nonproliferative benign diseases (NPF), 25 usual epithelial hyperplasia (UEH), 7 atypical ductal hyperplasia (ADH), and 27 breast normal tissues. An immunohistochemical approach was adopted, using the following antibodies: reactive with MUC1 variable number of tandem repeats (C595, HMFG2, and SM3 monoclonal antibodies), anti-MUC1-cytoplasmic tail polyclonal antibody (CT33), and anti-carbohydrate antigens (sialyl Lewis x, Lewis x, Lewis y, Tn, and Thomsen-Friedenreich epitopes). Positive area of reaction, intensity, and pattern of expression were considered. A reactivity index was calculated as intensity (I) x 100+percentage of positive area (A). Statistical analysis comprised frequency analysis, P < 0.05, analysis of variance, and multiple correlation with principal component analysis. All samples expressed MUC1, detected by at least one anti-MUC1 antibody whereas Lewis x was the carbohydrate antigen most frequently found in all groups whereas variable number of tandem repeats MUC1 and Lewis x showed the highest correlation: 93% of normal samples, 62.5% of NPF, 87% of FA, 85% of UEH, and finally 80% of ADH. Although principal component analysis using reactivity indexes explained only 39% of data variability, normal samples appeared grouped and separated from benign breast diseases, which remained spread. Thomsen-Friedenreich was the only antigen that showed an increased tendency for positive expression and intensity from NPF through FA, UEH to ADH, whereas it was not detected in normals. With respect to the pattern of expression, an apical pattern was predominantly found in all the groups.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26218914"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19625949"
},
{
- "id": "pmid:25298419",
+ "id": "pmid:15944787",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25298419",
- "title": "Transethnic replication of association of CTG18.1 repeat expansion of TCF4 gene with Fuchs' corneal dystrophy in Chinese implies common causal variant.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15944787",
+ "title": "Polymorphism of the MUC1 mucin gene is associated with susceptibility to lung adenocarcinoma and poor prognosis.",
"type": "article-journal",
- "doi": "10.1167/iovs.14-15390",
+ "doi": "",
"authors": [
- ["Chao", "Xing"],
- ["Xin", "Gong"],
- ["Imran", "Hussain"],
- ["Chiea-Chuen", "Khor"],
- ["Donald T H", "Tan"],
- ["Tin", "Aung"],
- ["Jodhbir S", "Mehta"],
- ["Eranga N", "Vithana"],
- ["V Vinod", "Mootha"]
+ ["Kazuhiro", "Mitsuta"],
+ ["Akihito", "Yokoyama"],
+ ["Keiichi", "Kondo"],
+ ["Masamitsu", "Nakajima"],
+ ["Ken-ichi", "Arita"],
+ ["Nobuoki", "Kohno"]
],
- "publisher": "Investigative ophthalmology & visual science",
- "issn": "1552-5783",
- "date": "2014-10-08",
- "abstract": "To test the association between the CTG18.1 trinucleotide repeat expansion of TCF4 gene and Fuchs' endothelial corneal dystrophy (FECD) in a Chinese population.",
+ "publisher": "Oncology reports",
+ "issn": "1021-335X",
+ "date": "2005-07-01",
+ "abstract": "MUC1 is a highly glycosylated glycoprotein that is often overexpressed in adenocarcinomas. MUC1 has molecular diversity because of a variable number of tandem repeats (from 25-125 repeats) in the extracellular domain of its core protein. MUC1 plays an important role in facilitating invasion and metastasis of malignant cells, and it also inhibits anti-cancer immune activity against malignant cells. We hypothesize that MUC1 allele length polymorphism (variable number of tandem repeats) is associated with development of lung adenocarcinoma. We evaluated MUC1 gene polymorphism using Southern blot analysis of peripheral blood from patients with non-small cell lung cancer (n=56), patients with benign respiratory disease (n=52), and healthy volunteers (n=52). We found that large MUC1 allele length was significantly associated with lung adenocarcinoma but not with squamous cell carcinoma of the lung. Adenocarcinoma patients with a homozygous large MUC1 genotype had a worse prognosis than patients with a heterozygous (large + small) MUC1 genotype or a homozygous small MUC1 genotype. These results suggest that the large MUC1 allele is associated with susceptibility to lung adenocarcinoma and poor prognosis.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25298419"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15944787"
},
{
- "id": "pmid:24255041",
+ "id": "pmid:11391628",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/24255041",
- "title": "Association and familial segregation of CTG18.1 trinucleotide repeat expansion of TCF4 gene in Fuchs' endothelial corneal dystrophy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11391628",
+ "title": "Antibody-dependent cell-mediated cytotoxicity can be induced by MUC1 peptide vaccination of breast cancer patients.",
"type": "article-journal",
- "doi": "10.1167/iovs.13-12611",
+ "doi": "10.1002/ijc.1286",
"authors": [
- ["V Vinod", "Mootha"],
- ["Xin", "Gong"],
- ["Hung-Chih", "Ku"],
- ["Chao", "Xing"]
+ ["F G", "Snijdewint"],
+ ["S", "von Mensdorff-Pouilly"],
+ ["A H", "Karuntu-Wanamarta"],
+ ["A A", "Verstraeten"],
+ ["P O", "Livingston"],
+ ["J", "Hilgers"],
+ ["P", "Kenemans"]
],
- "publisher": "Investigative ophthalmology & visual science",
- "issn": "1552-5783",
- "date": "2014-01-02",
- "abstract": "We tested the association between two intronic polymorphisms (CTG18.1 and rs613872) in TCF4 and Fuchs' endothelial corneal dystrophy (FECD), and analyzed their segregation patterns in families.",
+ "publisher": "International journal of cancer",
+ "issn": "0020-7136",
+ "date": "2001-07-01",
+ "abstract": "Human polymorphic epithelial mucin (PEM, MUC1) is a high molecular weight transmembrane glycoprotein expressed on the apical cell surface of glandular epithelium and is over-expressed and hypo-glycosylated in adenocarcinomas. The extracellular part of the molecule consists mainly of a variable number of 20 amino acid repeats that contain cryptic epitopes exposed in malignancy. The objective of our study was to determine whether humanized MUC1 MAbs and Abs induced by vaccination of breast cancer patients with MUC1 peptides can effect an antibody-dependent cell-mediated cytotoxicity (ADCC). An in vitro assay has been set up in which the breast tumor cell line ZR-75-1 is used as target and PBMC of healthy donors as effector cells. Different target and effector cells, as well as various MUC1 MAbs were tested to optimize the efficacy of the in vitro assay. The humanized MAb HuHMFG-1, which recognizes the PDTR sequence in the MUC1 tandem repeat, induced a strong cell-mediated cytotoxicity. Nine MUC1-expressing tumor cell lines, including 3 bone marrow-derived cell lines, as well as 2 MUC1-transfected cell lines were susceptible to different extent to MUC1 Ab-dependent killing. Large variations in the killing capacity of PBMC from healthy donors were found. The NK cells were the essential effector cells for the MUC1 Ab-dependent killing. Plasma samples with induced high levels of MUC1 Ab were obtained from breast cancer patients repeatedly immunized with a KLH-conjugated 33-mer or 106-mer MUC1 tandem repeat. Pre- and post-vaccinated plasma samples of these patients were compared in the ADCC assay and it could be clearly demonstrated that the induced MUC1 Abs can effect tumor cell killing. MUC1 Ab-dependent cell-mediated tumor cell killing may occur in vivo and the ADCC assay can be applied to monitor MUC1 vaccination trials.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24255041"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11391628"
},
{
- "id": "pmid:15368101",
+ "id": "pmid:9823312",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/15368101",
- "title": "SMARCA2 and THAP11: potential candidates for polyglutamine disorders as evidenced from polymorphism and protein-folding simulation studies.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/9823312",
+ "title": "Naturally processed class II epitope from the tumor antigen MUC1 primes human CD4+ T cells.",
"type": "article-journal",
- "doi": "10.1007/s10038-004-0194-8",
+ "doi": "",
"authors": [
- ["Neeraj", "Pandey"],
- ["Uma", "Mittal"],
- ["Achal K", "Srivastava"],
- ["Mitali", "Mukerji"]
- ],
- "publisher": "Journal of human genetics",
- "issn": "1434-5161",
- "date": "2004-09-10",
- "abstract": "CAG repeat expansion is the cause of an ever-increasing list of neurodegenerative disorders, especially hereditary ataxias. However, genes responsible for 10-50% of the clinically diagnosed ataxias are still unidentified in different populations. Traditional linkage and repeat expansion-detection based methods complemented with human genome sequence and expression information can now accelerate the pace of identification of putative disease candidates. We have analyzed two CAG repeat containing loci, human SMARCA2 and THAP11, which are expressed in the brain as putative candidates for SCAs, using computational as well as polymorphism scanning approaches. Both loci exhibited features characteristic of genes associated with repeat disorders. These loci are polymorphic with respect to size and interruption pattern in the Indian population. Furthermore, computational analysis of glutamine-stretch embedded domains in the respective proteins predicted these regions to be \"natively unfolded\" beyond a threshold of 40 glutamines. Comparative genome analysis suggested a stabilizing influence of CAA interspersions in repeat tract in THAP11 but not in SMARCA2. Although repeat expansion could not be detected within these genes in unidentified ataxia patients reported in India, we suggest that these loci be screened in other populations, as there is a wide heterogeneity in the prevalence of these disorders in different populations.",
+ ["E M", "Hiltbold"],
+ ["P", "Ciborowski"],
+ ["O J", "Finn"]
+ ],
+ "publisher": "Cancer research",
+ "issn": "0008-5472",
+ "date": "1998-11-15",
+ "abstract": "Epithelial cell mucin MUC1 is expressed on adenocarcinomas in an underglycosylated form that serves as a tumor antigen in breast, pancreatic, ovarian, and other tumors. Two predominant MUC1-specific immune responses are found in patients: CD8+ CTLs, which recognize tandemly repeated epitopes on the MUC1 protein core, and IgM antibodies. There have been no reports to date of MUC1-specific CD4+ T-helper cells in cancer patients. We show here that MUC1-specific CD4+ T cells are neither deleted nor tolerized and that CD4+ T cell responses can be generated when an appropriate soluble form of MUC1 is used. Naive CD4+ T cells from healthy donors were primed in vitro to a synthetic MUC1 peptide of 100 amino acids, representing five unglycosylated tandem repeats, presented by dendritic cells. They produced IFN-gamma and had moderate cytolytic activity. We identified one core peptide sequence, PGSTAPPAHGVT, that elicits this response when it is presented by HLA-DR3.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15368101"
-},
-{
- "id": "pmid:40589716",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/40589716",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:40589716']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:9823312"
},
{
- "id": "pmid:38411001",
+ "id": "pmid:7628867",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/38411001",
- "title": "Real-time",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/7628867",
+ "title": "DNA methylation status of the MUC1 gene coding for a breast-cancer-associated protein.",
"type": "article-journal",
- "doi": "10.1039/d3an02107f",
+ "doi": "10.1002/ijc.2910620303",
"authors": [
- ["Jiejie", "Guang"],
- ["Shan", "Wang"],
- ["Bingyuan", "Fan"],
- ["Ziyao", "Yu"],
- ["Yahui", "Gao"],
- ["Jinru", "Pan"],
- ["Junting", "Xi"],
- ["Wei", "Meng"],
- ["Fang", "Hu"]
+ ["S", "Zrihan-Licht"],
+ ["M", "Weiss"],
+ ["I", "Keydar"],
+ ["D H", "Wreschner"]
],
- "publisher": "The Analyst",
- "issn": "1364-5528",
- "date": "2024-03-25",
- "abstract": "A biosensor that can detect biomarkers accurately, quickly, and conveniently is important for the diagnosis of various diseases. However, most of the existing detection methods require sample extraction, which makes it difficult to detect and image intracellular molecules or to detect two different types of biomarkers simultaneously. In this study, we constructed a DNA tetrahedral nanoprobe (DTP) capable of detecting both miR378 and telomerase, both of which are tumor markers. In the presence of miR378, FAM on the molecular beacon of DTP fluoresced",
+ "publisher": "International journal of cancer",
+ "issn": "0020-7136",
+ "date": "1995-07-28",
+ "abstract": "The MUC1 gene codes for protein products that are highly expressed in human breast-cancer tissue and that serve as tumor markers for disease progression. The factors contributing to the disease-specific over-expression of the MUC1 gene are under intensive investigation and are yet to be determined. A large transcribed region of the human MUC1 gene is a CpG island that consists of 60-bp tandemly repeating units, each of which contains one SmaI restriction site. The methylation status of regulatory regions, upstream to the transcriptional start site, is essential for the regulation of gene expression. We therefore evaluated whether the methylation status of the various regions of the MUC1 gene may affect its expression. Using SmaI, and its isoschizomer XmaI endonucleases, we demonstrated that in peripheral-blood leukocytes (PBL-DNA) that do not express the MUC1 gene, the repeat array is completely methylated, whereas the same sequences are entirely non-methylated in breast-tumor-tissue DNA (BT-DNA). In contrast, sequences upstream and downstream to the repeat array showed no difference in the methylation pattern in PBL-DNA and BT-DNA. Hypomethylation within the repeat array was also observed in other epithelial tissues that express the MUC1 gene at much lower levels to those seen in breast-cancer tissue. These studies demonstrate that hypomethylation of the tandem repeat array is an absolute requirement for MUC1 gene expression in epithelial tissues, although in breast-cancer tissue additional regulatory mechanisms must pertain for its over-expression.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38411001"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:7628867"
},
{
- "id": "pmid:38134936",
+ "id": "pmid:32407596",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/38134936",
- "title": "Immune determinants of CAR-T cell expansion in solid tumor patients receiving GD2 CAR-T cell therapy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/32407596",
+ "title": "Rapid Diagnosis of Spinocerebellar Ataxia 36 in a Three-Generation Family Using Short-Read Whole-Genome Sequencing Data.",
"type": "article-journal",
- "doi": "10.1016/j.ccell.2023.11.011",
+ "doi": "10.1002/mds.28105",
"authors": [
- ["Sabina", "Kaczanowska"],
- ["Tara", "Murty"],
- ["Ahmad", "Alimadadi"],
- ["Cristina F", "Contreras"],
- ["Caroline", "Duault"],
- ["Priyanka B", "Subrahmanyam"],
- ["Warren", "Reynolds"],
- ["Norma A", "Gutierrez"],
- ["Reema", "Baskar"],
- ["Catherine J", "Wu"],
- ["Franziska", "Michor"],
- ["Jennifer", "Altreuter"],
- ["Yang", "Liu"],
- ["Aashna", "Jhaveri"],
- ["Vandon", "Duong"],
- ["Hima", "Anbunathan"],
- ["Claire", "Ong"],
- ["Hua", "Zhang"],
- ["Radim", "Moravec"],
- ["Joyce", "Yu"],
- ["Roshni", "Biswas"],
- ["Stephen", "Van Nostrand"],
- ["James", "Lindsay"],
- ["Mina", "Pichavant"],
- ["Elena", "Sotillo"],
- ["Donna", "Bernstein"],
- ["Amanda", "Carbonell"],
- ["Joanne", "Derdak"],
- ["Jacquelyn", "Klicka-Skeels"],
- ["Julia E", "Segal"],
- ["Eva", "Dombi"],
- ["Stephanie A", "Harmon"],
- ["Baris", "Turkbey"],
- ["Bita", "Sahaf"],
- ["Sean", "Bendall"],
- ["Holden", "Maecker"],
- ["Steven L", "Highfill"],
- ["David", "Stroncek"],
- ["John", "Glod"],
- ["Melinda", "Merchant"],
- ["Catherine C", "Hedrick"],
- ["Crystal L", "Mackall"],
- ["Sneha", "Ramakrishna"],
- ["Rosandra N", "Kaplan"]
+ ["Haloom", "Rafehi"],
+ ["David J", "Szmulewicz"],
+ ["Kate", "Pope"],
+ ["Mathew", "Wallis"],
+ ["John", "Christodoulou"],
+ ["Susan M", "White"],
+ ["Martin B", "Delatycki"],
+ ["Paul J", "Lockhart"],
+ ["Melanie", "Bahlo"]
],
- "publisher": "Cancer cell",
- "issn": "1878-3686",
- "date": "2023-12-21",
- "abstract": "Chimeric antigen receptor T\u00a0cells (CAR-Ts) have remarkable efficacy in liquid tumors, but limited responses in solid tumors. We conducted a Phase I trial (NCT02107963) of GD2 CAR-Ts (GD2-CAR.OX40.28.z.iC9), demonstrating feasibility and safety of administration in children and young adults with osteosarcoma and neuroblastoma. Since CAR-T efficacy requires adequate CAR-T expansion, patients were grouped into good or poor expanders across dose levels. Patient samples were evaluated by multi-dimensional proteomic, transcriptomic, and epigenetic analyses. T\u00a0cell assessments identified naive T\u00a0cells in pre-treatment apheresis associated with good expansion, and exhausted T\u00a0cells in CAR-T products with poor expansion. Myeloid cell assessment identified CXCR3",
+ "publisher": "Movement disorders : official journal of the Movement Disorder Society",
+ "issn": "1531-8257",
+ "date": "2020-05-14",
+ "abstract": "Spinocerebellar ataxias are often caused by expansions of short tandem repeats. Recent methodological advances have made repeat expansion (RE) detection with whole-genome sequencing (WGS) feasible.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38134936"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32407596"
},
{
- "id": "pmid:34526668",
+ "id": "pmid:39920690",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/34526668",
- "title": "Elevated common variant genetic risk for tourette syndrome in a densely-affected pedigree.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/39920690",
+ "title": "uN2CpolyG-mediated p65 nuclear sequestration suppresses the NF-\u03baB-NLRP3 pathway in neuronal intranuclear inclusion disease.",
"type": "article-journal",
- "doi": "10.1038/s41380-021-01277-w",
+ "doi": "10.1186/s12964-025-02079-1",
"authors": [
- ["Matthew", "Halvorsen"],
- ["Jin", "Szatkiewicz"],
- ["Poorva", "Mudgal"],
- ["Dongmei", "Yu"],
- ["Ashley E", "Nordsletten"],
- ["David", "Mataix-Cols"],
- ["Carol A", "Mathews"],
- ["Jeremiah M", "Scharf"],
- ["Manuel", "Mattheisen"],
- ["Mary M", "Robertson"],
- ["Andrew", "McQuillin"],
- ["James J", "Crowley"]
+ ["Yu", "Shen"],
+ ["Kaiyan", "Jiang"],
+ ["Dandan", "Tan"],
+ ["Min", "Zhu"],
+ ["Yusen", "Qiu"],
+ ["Pencheng", "Huang"],
+ ["Wenquan", "Zou"],
+ ["Jianwen", "Deng"],
+ ["Zhaoxia", "Wang"],
+ ["Ying", "Xiong"],
+ ["Daojun", "Hong"]
],
- "publisher": "Molecular psychiatry",
- "issn": "1476-5578",
- "date": "2021-09-15",
- "abstract": "Tourette syndrome (TS) is a highly heritable neuropsychiatric disorder with complex patterns of genetic inheritance. Recent genetic findings in TS have highlighted both numerous common variants with small effects and a few rare variants with moderate or large effects. Here we searched for genetic causes of TS in a large, densely-affected British pedigree using a systematic genomic approach. This pedigree spans six generations and includes 122 members, 85 of whom were individually interviewed, and 53 of whom were diagnosed as \"cases\" (consisting of 28 with definite or probable TS, 20 with chronic multiple tics [CMT], and five with obsessive-compulsive behaviors [OCB]). A total of 66 DNA samples were available (25 TS, 15 CMT, 4 OCB cases, and 22 unaffecteds) and all were genotyped using a dense single nucleotide polymorphism (SNP) array to identify shared segments, copy number variants (CNVs), and to calculate genetic risk scores. Eight cases were also whole genome sequenced to test whether any rare variants were shared identical by descent. While we did not identify any notable CNVs, single nucleotide variants, indels or repeat expansions of near-Mendelian effect, the most distinctive feature of this family proved to be an unusually high load of common risk alleles for TS. We found that cases within this family carried a higher load of TS common variant risk similar to that previously found in unrelated TS cases. Thus far, the strongest evidence from genetic data for contribution to TS risk in this family comes from multiple common risk variants rather than one or a few variants of strong effect.",
+ "publisher": "Cell communication and signaling : CCS",
+ "issn": "1478-811X",
+ "date": "2025-02-07",
+ "abstract": "Neuronal intranuclear inclusion disease (NIID) is genetically linked to CGG repeat expansion in the 5'-untranslated region of the NOTCH2NLC gene, with nascent polyglycine-containing protein (uN2CpolyG) identified as a primary pathogenic factor. Emerging clinical evidence suggests that inflammation contributes to NIID pathogenesis, yet the underlying molecular mechanisms remain elusive. This study aimed to elucidate the molecular interaction between uN2CpolyG and the NF-\u03baB-NLRP3 pathway.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34526668"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39920690"
},
{
- "id": "pmid:34197619",
+ "id": "pmid:37365282",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/34197619",
- "title": "Strand-specific effect of Rad26 and TFIIS in rescuing transcriptional arrest by CAG trinucleotide repeat slip-outs.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/37365282",
+ "title": "The genetic and clinical spectrum in a cohort of 39 families with complex inherited peripheral neuropathies.",
"type": "article-journal",
- "doi": "10.1093/nar/gkab573",
+ "doi": "10.1007/s00415-023-11821-z",
"authors": [
- ["Jun", "Xu"],
- ["Jenny", "Chong"],
- ["Dong", "Wang"]
+ ["Mengli", "Wang"],
+ ["Honglan", "Yang"],
+ ["Zhiqiang", "Lin"],
+ ["Xiaobo", "Li"],
+ ["Lei", "Liu"],
+ ["Shunxiang", "Huang"],
+ ["Huadong", "Zhao"],
+ ["Xiying", "Zhu"],
+ ["Qiao", "Xiao"],
+ ["Ranhui", "Duan"],
+ ["Junling", "Wang"],
+ ["Stephan", "Zuchner"],
+ ["Beisha", "Tang"],
+ ["Ruxu", "Zhang"]
],
- "publisher": "Nucleic acids research",
- "issn": "1362-4962",
- "date": "2021-07-21",
- "abstract": "Transcription induced CAG repeat instability is associated with fatal neurological disorders. Genetic approaches found transcription-coupled nucleotide excision repair (TC-NER) factor CSB protein and TFIIS play critical roles in modulating the repeat stability. Here, we took advantage of an in vitro reconstituted yeast transcription system to investigate the underlying mechanism of RNA polymerase II (Pol II) transcriptional pausing/stalling by CAG slip-out structures and the functions of TFIIS and Rad26, the yeast ortholog of CSB, in modulating transcriptional arrest. We identified length-dependent and strand-specific mechanisms that account for CAG slip-out induced transcriptional arrest. We found substantial R-loop formation for the distal transcriptional pausing induced by template strand (TS) slip-out, but not non-template strand (NTS) slip-out. In contrast, Pol II backtracking was observed at the proximal transcriptional pausing sites induced by both NTS and TS slip-out blockage. Strikingly, we revealed that Rad26 and TFIIS can stimulate bypass of NTS CAG slip-out, but not TS slip-out induced distal pausing. Our biochemical results provide new insights into understanding the mechanism of CAG slip-out induced transcriptional pausing and functions of transcription factors in modulating transcription-coupled CAG repeat instability, which may pave the way for developing potential strategies for the treatment of repeat sequence associated human diseases.",
+ "publisher": "Journal of neurology",
+ "issn": "1432-1459",
+ "date": "2023-06-26",
+ "abstract": "With complicated conditions and a large number of potentially causative genes, the diagnosis of a patient with complex inherited peripheral neuropathies (IPNs) is challenging. To provide an overview of the genetic and clinical features of 39 families with complex IPNs from central south China and to optimize the molecular diagnosis approach to this group of heterogeneous diseases, a total of 39 index patients from unrelated families were enrolled, and detailed clinical data were collected. TTR Sanger sequencing, hereditary spastic paraplegia (HSP) gene panel, and dynamic mutation detection in spinocerebellar ataxia (SCAs) were performed according to the respective additional clinical features. Whole-exome sequencing (WES) was used in patients with negative or unclear results. Dynamic mutation detection in NOTCH2NLC and RCF1 was applied as a supplement to WES. As a result, an overall molecular diagnosis rate of 89.7% was achieved. All 21 patients with predominant autonomic dysfunction and multiple organ system involvement carried pathogenic variants in TTR, among which nine had c.349G\u2009>\u2009T (p.A97S) hotspot variants. Five out of 7 patients (71.4%) with muscle involvement harbored biallelic pathogenic variants in GNE. Five out of 6 patients (83.3%) with spasticity reached definite genetic causes in SACS, KIF5A, BSCL2, and KIAA0196, respectively. NOTCH2NLC GGC repeat expansions were identified in all three cases accompanied by chronic coughing and in one patient accompanied by cognitive impairment. The pathogenic variants, p.F284S and p.G111R in GNE, and p.K4326E in SACS, were first reported. In conclusion, transthyretin amyloidosis with polyneuropathy (ATTR-PN), GNE myopathy, and neuronal intranuclear inclusion disease (NIID) were the most common genotypes in this cohort of complex IPNs. NOTCH2NLC dynamic mutation testing should be added to the molecular diagnostic workflow. We expanded the genetic and related clinical spectrum of GNE myopathy and ARSACS by reporting novel variants.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34197619"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37365282"
},
{
- "id": "pmid:32813677",
+ "id": "pmid:36483830",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/32813677",
- "title": "Impact of parental origin of X-chromosome on clinical and biochemical profile in Turner syndrome.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/36483830",
+ "title": "Typical imaging manifestation of neuronal intranuclear inclusion disease in a man with unsteady gait: A case report.",
"type": "article-journal",
- "doi": "10.1515/jpem-2020-0104",
+ "doi": "10.12998/wjcc.v10.i33.12388",
"authors": [
- ["Rakhi", "Malhotra"],
- ["Rashmi", "Shukla"],
- ["Madhulika", "Kabra"],
- ["Yashdeep", "Gupta"],
- ["Viveka P", "Jyotsna"],
- ["Rajesh", "Khadgawat"]
+ ["Xue", "Gao"],
+ ["Zhi-Ding", "Shao"],
+ ["Lei", "Zhu"]
],
- "publisher": "Journal of pediatric endocrinology & metabolism : JPEM",
- "issn": "2191-0251",
- "date": "2020-09-25",
- "abstract": "Objectives To evaluate if the parental origin of X-chromosome has an impact on the phenotype and biochemical profile in Turner syndrome (TS). Result of the previous studies have been equivocal and could be attributable to the multicentric study design with different experts examining heterogeneous TS population of various ethnic background. Methods A cross-sectional single center study from Northern India. Fifty nine diagnosed subjects of TS and their parents participated in the study. Parental origin of intact X-chromosome was determined using 12 highly polymorphic short tandem repeats (STR) on X-chromosome. For the evaluation of parent-of-origin effects, typical phenotypic traits including congenital malformations, anthropometry, body composition by dual energy X-ray absorptiometry (DXA) and biochemical profile were compared. Clinical stigmata of TS in all subjects were examined by a single expert. Results The intact X-chromosome was of maternal origin (Xm) in 49.1% subjects while 50.9% had paternal origin (Xp). Skeletal anomalies were more common in Xm group, out of which prevalence of short neck and short fourth metatarsal reached statistical significance (p=0.04 and 0.01 respectively). A strong correlation was observed between subject's baseline height standard deviation score (Ht SDS) and paternal height (r=0.593, p<0.001), maternal height (r=0.564, p<0.001) and mid-parental height (MPH) (r=0.372, p=0.047) in Xp group. This effect was not seen in Xm subjects whose baseline Ht SDS showed no significant correlation with maternal height, paternal height or MPH. No differences were detected between the groups with regard to biochemical profile or body composition. Conclusions We speculate that the differences in skeletal anomalies and height correlations between Xm and Xp groups could be due to the modifying effect of epigenetic signature on short stature homeobox (SHOX) gene of Xm. SHOX gene is not modified on Xp thereby explaining the paucity of skeletal changes and height correlations in Xp subjects.",
+ "publisher": "World journal of clinical cases",
+ "issn": "2307-8960",
+ "date": "2022-11-26",
+ "abstract": "Neuronal intranuclear inclusion disease (NIID) is a rare neurological degenerative disorder with diverse manifestations and inadequate awareness. Only a few cases of NIID have been reported, and typical imaging findings can provide certain clues for the diagnosis of the disease. Furthermore, skin biopsy and genetic testing are important to confirm the diagnosis.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32813677"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36483830"
},
{
- "id": "pmid:32695278",
+ "id": "pmid:35772299",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/32695278",
- "title": "The Role of",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/35772299",
+ "title": "Generation of an induced pluripotent stem cell line (ZZUi036-A) derived from skin fibroblasts of a Neuronal intranuclear inclusion disease patient with GGC repeat expansion in the NOTCH2NLC gene.",
"type": "article-journal",
- "doi": "",
+ "doi": "10.1016/j.scr.2022.102844",
"authors": [
- ["Mohammad Hadi", "Abbasian"],
- ["Nafiseh", "Ansarinejad"],
- ["Bahareh", "Abbasi"],
- ["Masoud", "Iravani"],
- ["Tayeb", "Ramim"],
- ["Fahime", "Hamedi"],
- ["Ali M", "Ardekani"]
+ ["Jiadi", "Li"],
+ ["Yu", "Fan"],
+ ["Liyuan", "Fan"],
+ ["Fen", "Liu"],
+ ["Xiaoyan", "Hao"],
+ ["Mengjie", "Li"],
+ ["Chengyuan", "Mao"],
+ ["Yuming", "Xu"],
+ ["Changhe", "Shi"]
],
- "publisher": "Avicenna journal of medical biotechnology",
- "issn": "2008-2835",
- "date": "2020-01-01",
- "abstract": "The fluoropyrimidine drug 5-Fluorouracil (5-FU) and the prodrug capecitabine have been extensively used for treatment of many types of cancer including colorectal, gastric, head and neck. Approximately, 10 to 25% of patients suffer from severe fluoropyrimidine-induced toxicity. This may lead to dose reduction and treatment discontinuation. Pharmacogenetics research could be useful for the identification of predictive markers in chemotherapy treatment. The aim of the study was to investigate the role of five genetic polymorphisms within two genes (",
+ "publisher": "Stem cell research",
+ "issn": "1876-7753",
+ "date": "2022-06-15",
+ "abstract": "Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease characterized by cognitive impairment, extrapyramidal symptoms, white matter lesions and muscle weakness. The cause of NIID is a repeat amplification of a GGC mutation in the 5 ' untranslated region (UTR) of the NOTCH2NLC gene. Using the non-integrating Sendai virus to deliver the Klf4, OCT3/4, SOX2 and C-MYC factors, fibroblasts obtained from a NIID patient were reprogrammed to generate an induced pluripotent stem cell (iPSC) line (ZZUi036-A). Our approach provided a resource for the investigation of the mechanism of the disease, drug research, cell transplantation and gene therapy.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32695278"
-},
-{
- "id": "pmid:30533396",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/30533396",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:30533396']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35772299"
},
{
- "id": "pmid:30464574",
+ "id": "pmid:34243731",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/30464574",
- "title": "Influence of MSI and 18q LOH markers on capecitabine adjuvant monotherapy in colon cancer patients.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/34243731",
+ "title": "Coexistence of neuronal intranuclear inclusion disease and amyotrophic lateral sclerosis: an autopsy case.",
"type": "article-journal",
- "doi": "10.2147/pgpm.s172467",
+ "doi": "10.1186/s12883-021-02306-5",
"authors": [
- ["Nadica", "Matevska-Geshkovska"],
- ["Marija", "Staninova-Stojovska"],
- ["Aleksandra", "Kapedanovska-Nestorovska"],
- ["Natalija", "Petrushevska-Angelovska"],
- ["Milco", "Panovski"],
- ["Biljana", "Grozdanovska"],
- ["Nenad", "Mitreski"],
- ["Aleksandar", "Dimovski"]
+ ["Atsuhiko", "Sugiyama"],
+ ["Takahiro", "Takeda"],
+ ["Mizuho", "Koide"],
+ ["Hajime", "Yokota"],
+ ["Hiroki", "Mukai"],
+ ["Yoshihisa", "Kitayama"],
+ ["Kazumoto", "Shibuya"],
+ ["Nobuyuki", "Araki"],
+ ["Ai", "Ishikawa"],
+ ["Sagiri", "Isose"],
+ ["Kimiko", "Ito"],
+ ["Kazuhiro", "Honda"],
+ ["Yoshitaka", "Yamanaka"],
+ ["Terunori", "Sano"],
+ ["Yuko", "Saito"],
+ ["Kimihito", "Arai"],
+ ["Satoshi", "Kuwabara"]
],
- "publisher": "Pharmacogenomics and personalized medicine",
- "issn": "1178-7066",
- "date": "2018-11-01",
- "abstract": "The aim of this study was to evaluate whether pretreatment analysis of selected molecular markers can be used for the prediction of disease-free survival (DFS)/overall survival (OS) of capecitabine adjuvant monotherapy in colon cancer patients.",
+ "publisher": "BMC neurology",
+ "issn": "1471-2377",
+ "date": "2021-07-09",
+ "abstract": "Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease. Pathologically, it is characterized by eosinophilic hyaline intranuclear inclusions in the cells of the visceral organs as well as central, peripheral, and autonomic nervous system cells. Recently, a GGC repeat expansion in the NOTCH2NLC gene has been identified as the etiopathological agent of NIID. Interestingly, this GGC repeat expansion was also reported in some patients with a clinical diagnosis of amyotrophic lateral sclerosis (ALS). However, there are no autopsy-confirmed cases of concurrent NIID and ALS.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30464574"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34243731"
},
{
- "id": "pmid:29394274",
+ "id": "pmid:33026126",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/29394274",
- "title": "XRCC3 Thr241Met and TYMS variable number tandem repeat polymorphisms are associated with time-to-metastasis in colorectal cancer.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/33026126",
+ "title": "Low Prevalence of NOTCH2NLC GGC Repeat Expansion in White Patients with Movement Disorders.",
"type": "article-journal",
- "doi": "10.1371/journal.pone.0192316",
+ "doi": "10.1002/mds.28302",
"authors": [
- ["Yanjing", "He"],
- ["Michelle E", "Penney"],
- ["Amit A", "Negandhi"],
- ["Patrick S", "Parfrey"],
- ["Sevtap", "Savas"],
- ["Yildiz E", "Yilmaz"]
+ ["Wai Yan", "Yau"],
+ ["Jana", "Vandrovcova"],
+ ["Roisin", "Sullivan"],
+ ["Zhongbo", "Chen"],
+ ["Anna", "Zecchinelli"],
+ ["Roberto", "Cilia"],
+ ["Stefano", "Duga"],
+ ["Malgorzata", "Murray"],
+ ["Susana", "Carmona"],
+ ["Viorica", "Chelban"],
+ ["Hiroyuki", "Ishiura"],
+ ["Shoji", "Tsuji"],
+ ["Zane", "Jaunmuktane"],
+ ["Chris", "Turner"],
+ ["Nicholas W", "Wood"],
+ ["Henry", "Houlden"]
],
- "publisher": "PloS one",
- "issn": "1932-6203",
- "date": "2018-02-02",
- "abstract": "Metastasis is a major cause of mortality in cancer. Identifying prognostic factors that distinguish patients who will experience metastasis in the short-term and those that will be free of metastasis in the long-term is of particular interest in current medical research. The objective of this study was to examine if select genetic polymorphisms can differentiate colorectal cancer patients based on timing and long-term risk of metastasis.",
+ "publisher": "Movement disorders : official journal of the Movement Disorder Society",
+ "issn": "1531-8257",
+ "date": "2020-10-07",
+ "abstract": "The objective of this study was to determine the prevalence of the GGC-repeat expansion in NOTCH2NLC in whites presenting with movement disorders.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29394274"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:33026126"
},
{
- "id": "pmid:29321350",
+ "id": "pmid:31886491",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/29321350",
- "title": "Neuro-fuzzy model of homocysteine metabolism.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/31886491",
+ "title": "Essential phenotypes of NOTCH2NLC-related repeat expansion disorder.",
"type": "article-journal",
- "doi": "10.1007/s12041-017-0856-x",
+ "doi": "10.1093/brain/awz404",
"authors": [
- ["Shaik Mohammad", "Naushad"],
- ["Akella Radha", "Rama Devi"],
- ["Sriraman", "Nivetha"],
- ["Ganapathy", "Lakshmitha"],
- ["Alex Balraj", "Stanley"],
- ["Tajamul", "Hussain"],
- ["Vijay Kumar", "Kutala"]
+ ["Ana", "Westenberger"],
+ ["Christine", "Klein"]
],
- "publisher": "Journal of genetics",
- "issn": "0973-7731",
- "date": "2017-12-01",
- "abstract": "In view of well-documented association of hyperhomocysteinaemia with a wide spectrum of diseases and higher incidence of vitamin deficiencies in Indians, we proposed a mathematical model to forecast the role of demographic and genetic variables in influencing homocysteinemetabolism and investigated the influence of life style modulations in controlling homocysteine levels. Total plasma homocysteine levels were measured in fasting samples using reverse phase HPLC. Multiple linear regression (MLR) and neuro-fuzzy models were developed. The MLR model explained 64% variability in homocysteine, while the neurofuzzy model showed higher accuracy in predicting homocysteine with a mean absolute error of 0.00002 \u03bcmol/L. Methylene tetrahydrofolate reductase (MTHFR) C677T, 5-methyltetrahydrofolate homocysteine methyltransferase (MTR) A2756G and 5- methyltetrahydrofolate homocysteine methyltransferase reductase (MTRR) A66G were shown to be positively associatiated with homocysteine, while nonvegetarian diet, serine hydroxymethyltransferase 1 (SHMT1) C1420T and TYMS 5'-UTR 28 bp tandem repeat exhibited negative association with homocysteine. The protective role of SHMT1 C1420T was attributed to more H-bonding interactions in the mutant modelled compared to the wild type, as shown through in silico analysis. To conclude, polymorphisms in genes regulating remethylation of homocysteine strongly influence homocysteine levels. The restoration of one-carbon homeostasis by SHMT1 C1420T or increased flux of folate towards remethylation due to TYMS 5'-UTR 28 bp tandem repeat or nonvegetarian diet can lower homocysteine levels.",
+ "publisher": "Brain : a journal of neurology",
+ "issn": "1460-2156",
+ "date": "2020-01-01",
+ "abstract": "",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29321350"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31886491"
},
{
- "id": "pmid:28280649",
+ "id": "pmid:35859342",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/28280649",
- "title": "First Case of Foot Drop Associated with Capecitabine in a Patient with Thymidylate Synthase Polymorphism.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/35859342",
+ "title": "Muscle ultrasound is a sensitive biomarker in oculopharyngeal muscular dystrophy.",
"type": "article-journal",
- "doi": "10.7759/cureus.995",
+ "doi": "10.1002/mus.27679",
"authors": [
- ["Andrew B", "Wilks"],
- ["Muhammad W", "Saif"]
+ ["Rosemarie H M J M", "Kroon"],
+ ["Johanna G", "Kalf"],
+ ["Rutger L", "Meijers"],
+ ["Bert J M", "de Swart"],
+ ["Ian G M", "Cameron"],
+ ["Jonne", "Doorduin"],
+ ["Nens", "van Alfen"],
+ ["Baziel G M", "van Engelen"],
+ ["Corinne G C", "Horlings"]
],
- "publisher": "Cureus",
- "issn": "2168-8184",
- "date": "2017-01-24",
- "abstract": "Capecitabine, an oral prodrug of 5-FU, has been approved by the FDA for use in patients with breast and colon cancers. In addition, capecitabine is commonly used in patients with other malignancies such as pancreatic, gastroesophageal, and hepatobiliary tract cancers. Though cerebellar toxicity is a rare but well-known side effect of intravenous 5-FU therapy, peripheral neuropathy with capecitabine has only been described in rare cases. In this case report, we describe a 79-year-old patient with locally advanced adenocarcinoma of the pancreas undergoing chemoradiation therapy with capecitabine who developed peripheral sensorimotor neuropathy. To the best of our knowledge, this is the first patient in the literature who was found to have two mutations (2R) of a 28 base-pair tandem repeat in the 5' promoter enhancer region (5'-TSER) on both alleles (2R/2R) of thymidylate synthetase (TYMS) gene, possibly responsible for the neurotoxicity.",
+ "publisher": "Muscle & nerve",
+ "issn": "1097-4598",
+ "date": "2022-08-12",
+ "abstract": "Oculopharyngeal muscular dystrophy (OPMD) is a late-onset, progressive muscle disease. Quantitative muscle ultrasound (QMUS) assesses structural changes in muscles and is a sensitive biomarker in neuromuscular disorders. Our aim of this study was to determine whether QMUS can detect muscle pathology and can be used as longitudinal imaging biomarker in OPMD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28280649"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35859342"
},
{
- "id": "pmid:28074308",
+ "id": "pmid:18367172",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/28074308",
- "title": "Influence of TS and ABCB1\u00a0gene polymorphisms on survival outcomes of 5\u2011FU-based chemotherapy in a\u00a0Chinese population of advanced gastric cancer patients.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/18367172",
+ "title": "PABPN1 polyalanine tract deletion and long expansions modify its aggregation pattern and expression.",
"type": "article-journal",
- "doi": "10.1007/s00508-016-1147-x",
+ "doi": "10.1016/j.yexcr.2008.02.005",
"authors": [
- ["Jun", "Chen"],
- ["Xueming", "Ying"],
- ["Ling", "Zhang"],
- ["Xiaojun", "Xiang"],
- ["Jianping", "Xiong"]
+ ["Arnaud F", "Klein"],
+ ["Mitsuru", "Ebihara"],
+ ["Christine", "Alexander"],
+ ["Marie-Jos\u00e9e", "Dicaire"],
+ ["A Marie-Jos\u00e9e", "Sasseville"],
+ ["Yves", "Langelier"],
+ ["Guy A", "Rouleau"],
+ ["Bernard", "Brais"]
],
- "publisher": "Wiener klinische Wochenschrift",
- "issn": "1613-7671",
- "date": "2017-01-10",
- "abstract": "To investigate the impacts of gene variations on survival outcomes of advanced gastric cancer (AGC) patients treated with 5\u2011fluorouracil (5-FU)-based chemotherapy, we analyzed the associations of 2 indels of the TS gene rs34743033 (double or triple tandem repeats of a\u00a028\u2009bp sequence in 5'-UTR, denoted as 2R or 3R allele) and rs16430 (a\u00a06\u2009bp variation at 1494\u2009bp in 3'-UTR, denoted as ins6 or del6\u00a0allele) and 2 single nucleotide polymorphisms (SNPs) of ABCB1gene rs2032582 in exon\u00a021 and rs1045642 in exon\u00a026, with clinical outcomes after 5\u2011FU treatment. Generally, indels rs34743033 and rs16430 were genotyped by PCR and polyacrylamide gel electrophoresis assay and SNPs rs2032582 and rs1045642 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in 110\u00a0Chinese AGC patients post-chemotherapy. Cox regression analysis was used to analyze the risk factors affecting patient survival. As a\u00a0result, rs34743033, rs1045642 and rs2032582 were shown to be significantly associated with overall survival (P\u00a0< 0.05), and associations between the four polymorphisms with disease-free survival were also observed (P\u00a0< 0.05). Moreover, we found that genotypes rs34743033 3R/2R, rs16430 ins6/del6, rs1045642 CC or CT, and rs2032582\u00a0GG were beneficial predictors of clinical treatment outcome in AGC patients, suggesting some clinical implications in chemotherapy of a\u00a0Chinese population.",
+ "publisher": "Experimental cell research",
+ "issn": "0014-4827",
+ "date": "2008-02-23",
+ "abstract": "Expansions of a (GCN)10/polyalanine tract in the Poly(A) Binding Protein Nuclear 1 (PABPN1) cause autosomal dominant oculopharyngeal muscular dystrophy (OPMD). In OPMD muscles, as in models, PABPN1 accumulates in intranuclear inclusions (INIs) whereas in other diseases caused by similar polyalanine expansions, the mutated proteins have been shown to abnormally accumulate in the cytoplasm. This study presents the impact on the subcellular localization of PABPN1 produced by large expansions or deletion of its polyalanine tract. Large tracts of more than 24 alanines result in the nuclear accumulation of PABPN1 in SFRS2-positive functional speckles and a significant decline in cell survival. These large expansions do not cause INIs formation nor do they lead to cytoplasmic accumulation. Deletion of the polyalanine tract induces the formation of aggregates that are located on either side and cross the nuclear membrane, highlighting the possible role of the N-terminal polyalanine tract in PABPN1 nucleo-cytoplasmic transport. We also show that even though five other proteins with polyalanine tracts tend to aggregate when over-expressed they do not co-aggregate with PABPN1 INIs. This study presents the first experimental evidence that there may be a relative loss of function in OPMD by decreasing the availability of PABPN1 through an INI-independent mechanism.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28074308"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18367172"
},
{
- "id": "pmid:27864985",
+ "id": "pmid:12673802",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/27864985",
- "title": "Telomeric repeat-containing RNA (TERRA) related to polycystic ovary syndrome (PCOS).",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/12673802",
+ "title": "Oculopharyngeal muscular dystrophy (OPMD) due to a small duplication in the PABPN1 gene.",
"type": "article-journal",
- "doi": "10.1111/cen.13283",
+ "doi": "10.1002/humu.9138",
"authors": [
- ["Caiqin", "Wang"],
- ["Fengxian", "Shen"],
- ["Yuning", "Zhu"],
- ["Yuying", "Fang"],
- ["Shiming", "Lu"]
+ ["Barbara M", "van der Sluijs"],
+ ["Baziel G M", "van Engelen"],
+ ["Lies H", "Hoefsloot"]
],
- "publisher": "Clinical endocrinology",
- "issn": "1365-2265",
- "date": "2016-12-19",
- "abstract": "Telomeric repeat-containing RNA (TERRA) participates in the regulation of telomere length, and leucocyte telomere length (LTL) plays an important role in the pathophysiology of polycystic ovary syndrome (PCOS), but little is known about the role of TERRA in PCOS.",
+ "publisher": "Human mutation",
+ "issn": "1098-1004",
+ "date": "2003-05-01",
+ "abstract": "Oculopharyngeal muscular dystrophy (OPMD) is a late onset autosomal dominant muscle disorder. The OPMD-locus has been mapped to chromosome 14q11.2-q13. The polyadenylate binding protein nuclear 1 (PABPN1; PABP2) gene has been identified as the mutated gene. The mutation consists of a short meiotically stable trinucleotide repeat in the first exon of PABPN1 gene. We have investigated Dutch OPMD patients from four unrelated families and identified a new mutation in two of the four families. Instead of a repeat expansion we found a duplication in the first exon of the PABPN1 gene (c.27_28ins12, p.11_12insAAAA). The identification of this new mutation supports the theory of unequal crossing-over as molecular mechanism causing the mutation in the PABPN1 gene responsible for OPMD, and not the slippage model.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:27864985"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12673802"
},
{
- "id": "pmid:29767611",
+ "id": "pmid:34012823",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/29767611",
- "title": "Tandem repeats of TSER significantly influence the efficacy of 5-fluorouracil in the treatment of plantar warts.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/34012823",
+ "title": "Congenital central hypoventilation syndrome in neonates: report of fourteen new cases and a review of the literature.",
"type": "article-journal",
- "doi": "10.2217/pme-2015-0014",
+ "doi": "10.21037/tp-20-303",
"authors": [
- ["Yue", "Zhao"],
- ["Wangqing", "Chen"],
- ["Wu", "Zhu"],
- ["Jie", "Li"],
- ["Juan", "Su"],
- ["Shuang", "Zhao"],
- ["Mingliang", "Chen"],
- ["Jianglin", "Zhang"],
- ["Aiyuan", "Guo"],
- ["Siyu", "Yan"],
- ["Xingchen", "Zhou"],
- ["Xinwei", "Kuang"],
- ["Zhaoqian", "Liu"],
- ["Dan", "Luo"],
- ["Todd C", "Knepper"],
- ["Yijing", "He"],
- ["Xiang", "Chen"]
+ ["Mei", "Mei"],
+ ["Lin", "Yang"],
+ ["Yulan", "Lu"],
+ ["Laishuan", "Wang"],
+ ["Guoqiang", "Cheng"],
+ ["Yun", "Cao"],
+ ["Chao", "Chen"],
+ ["Liling", "Qian"],
+ ["Wenhao", "Zhou"]
],
- "publisher": "Personalized medicine",
- "issn": "1744-828X",
- "date": "2016-04-26",
- "abstract": "To identify potential genetic risk markers associated with 5-fluorouracil (5-FU) treatment outcomes in plantar warts patients.",
+ "publisher": "Translational pediatrics",
+ "issn": "2224-4344",
+ "date": "2021-04-01",
+ "abstract": "Congenital central hypoventilation syndrome (CCHS) is a rare autosomal dominant disorder caused by pathogenic variants in paired-like homeobox 2B (",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:29767611"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:34012823"
},
{
- "id": "pmid:26745074",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/26745074",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:26745074']' timed out after 3 seconds"
+ "id": "pmid:26011159",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26011159",
+ "title": "Treatment of neuroblastoma in congenital central hypoventilation syndrome with a PHOX2B polyalanine repeat expansion mutation: New twist on a neurocristopathy syndrome.",
+ "type": "article-journal",
+ "doi": "10.1002/pbc.25572",
+ "authors": [
+ ["Amy E", "Armstrong"],
+ ["Debra E", "Weese-Mayer"],
+ ["Amir", "Mian"],
+ ["John M", "Maris"],
+ ["Vandana", "Batra"],
+ ["Yasmin", "Gosiengfiao"],
+ ["Jennifer", "Reichek"],
+ ["Mary Beth", "Madonna"],
+ ["Jonathan W", "Bush"],
+ ["Richard M", "Shore"],
+ ["David O", "Walterhouse"]
+ ],
+ "publisher": "Pediatric blood & cancer",
+ "issn": "1545-5017",
+ "date": "2015-05-22",
+ "abstract": "Neuroblastoma in patients with congenital central hypoventilation syndrome (CCHS) as part of a neurocristopathy syndrome is a rare finding and has only been associated with paired-like homeobox 2b (PHOX2B) non-polyalanine-repeat-expansion mutations. To the best of our knowledge, we report the first case of a child with CCHS and Hirschsprung disease who had a PHOX2B polyalanine-repeat-expansion mutation (PARM) (genotype 20/33) and developed high-risk neuroblastoma. We further describe his treatment including chemotherapy and therapeutic I(131) -metaiodobenzylguanidine. This case highlights the need to consider neuroblastoma in patients with CCHS and the longest PHOX2B PARMs and to individualize treatment based on co-morbidities.",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26011159"
},
{
- "id": "pmid:26189437",
+ "id": "pmid:19881470",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/26189437",
- "title": "Increased risk of severe fluoropyrimidine-associated toxicity in patients carrying a G to C substitution in the first 28-bp tandem repeat of the thymidylate synthase 2R allele.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19881470",
+ "title": "Polyalanine expansion of PHOX2B in congenital central hypoventilation syndrome: rs17884724:A>C is associated with 7-alanine expansion.",
"type": "article-journal",
- "doi": "10.1002/ijc.29694",
+ "doi": "10.1038/jhg.2009.109",
"authors": [
- ["Didier", "Meulendijks"],
- ["Bart A W", "Jacobs"],
- ["Abidin", "Aliev"],
- ["Dick", "Pluim"],
- ["Erik", "van Werkhoven"],
- ["Maarten J", "Deenen"],
- ["Jos H", "Beijnen"],
- ["Annemieke", "Cats"],
- ["Jan H M", "Schellens"]
+ ["Hiroko", "Arai"],
+ ["Tesshu", "Otagiri"],
+ ["Ayako", "Sasaki"],
+ ["Kazuo", "Umetsu"],
+ ["Kiyoshi", "Hayasaka"]
],
- "publisher": "International journal of cancer",
- "issn": "1097-0215",
- "date": "2015-10-01",
- "abstract": "The fluoropyrimidines act by inhibiting thymidylate synthase (TS). Recent studies have shown that patients' risk of severe fluoropyrimidine-associated toxicity is affected by polymorphisms in the 5'-untranslated region of TYMS, the gene encoding TS. A G>C substitution in the promoter enhancer region of TYMS, rs183205964 (known as the 2RC allele), markedly reduces TS activity in vitro, but its clinical relevance is unknown. We determined rs183205964 in 1605 patients previously enrolled in a prospective multicenter study. Associations between putative low TS expression genotypes (3RC/2RC, 2RG/2RC, and 2RC/2RC) and severe toxicity were investigated using univariable and multivariable logistic regression. Activity of TS and TYMS gene expression were determined in peripheral blood mononuclear cells (PBMCs) of a patient carrying genotype 2RC/2RC and of a control group of healthy individuals. Among 1,605 patients, 28 patients (1.7%) carried the 2RC allele. Twenty patients (1.2%) carried a risk-associated genotype (2RG/2RC, n=13; 3RC/2RC, n=6; and 2RC/2RC, n=1), the eight remaining patients had genotype 3RG/2RC. Early severe toxicity and toxicity-related hospitalization were significantly more frequent in risk-associated genotype carriers (OR 3.0, 95%CI 1.04-8.93, p=0.043 and OR 3.8, 95%CI 1.19-11.9, p=0.024, respectively, in multivariable analysis). The patient with genotype 2RC/2RC was hospitalized twice and had severe febrile neutropenia, diarrhea, and hand-foot syndrome. Baseline TS activity and gene expression in PBMCs of this patient, and a healthy individual with the 2RC allele, were found to be within the normal range. Our study suggests that patients carrying rs183205964 are at strongly increased risk of severe, potentially life-threatening, toxicity when treated with fluoropyrimidines.",
+ "publisher": "Journal of human genetics",
+ "issn": "1435-232X",
+ "date": "2009-10-30",
+ "abstract": "With congenital central hypoventilation syndrome (CCHS), most patients have a de novo 5-13 polyalanine expansion mutation in PHOX2B. We reported previously that de novo polyalanine expansion mutations were of paternal origin and were derived from unequal sister chromatid exchange during spermatogenesis in six and four informative families, respectively. In this study, we analyzed the relationship between haplotypes and de novo polyalanine expansion in PHOX2B and found that haplotypes carrying rs17884724:A>C were detected frequently in 7-alanine expanded (27-alanine) mutant alleles, which are the most prevalent mutations in CCHS. The allele with rs17884724:A>C made fewer nucleotide mismatches in the misalignment at crossing-over than the allele without rs17884724:A>C. The high frequency of rs17884724:A>C in 7-alanine expansion (27-alanine) mutations also supported the unequal crossover mechanism for polyalanine expansion. We also confirmed the paternal origin of de novo polyalanine expansion mutation and unequal sister chromatid exchange association in three more patients. In spite of paternal bias, the paternal age effect on CCHS incidence was not observed. De novo polyalanine expansion mutations are mainly derived from unequal sister chromatid exchange during spermatogenesis because of replication and/or repair systems that are specific for spermatogenesis.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26189437"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19881470"
},
{
- "id": "pmid:25536611",
+ "id": "pmid:23493802",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25536611",
- "title": "The influence of methylenetetrahydrofolate reductase and thymidylate synthetase gene polymorphisms on lung adenocarcinoma occurrence.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/23493802",
+ "title": "The POLG Gene Polymorphism in Iranian Varicocele-Associated Infertility Patients.",
"type": "article-journal",
"doi": "",
"authors": [
- ["Milena", "Cavic"],
- ["Ana", "Krivokuca"],
- ["Jelena", "Spasic"],
- ["Ksenija", "Brotto"],
- ["Emina", "Malisic"],
- ["Davorin", "Radosavljevic"],
- ["Sinisa", "Radulovic"],
- ["Radmila", "Jankovic"]
+ ["Mohammad Mehdi", "Heidari"],
+ ["Mehri", "Khatami"],
+ ["Ali Reza", "Talebi"]
],
- "publisher": "Journal of B.U.ON. : official journal of the Balkan Union of Oncology",
- "issn": "1107-0625",
- "date": "2014-01-01",
- "abstract": "Methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthetase (TYMS) are suggested as risk factors for lung cancer. The purpose of this study was to analyze the association of MTHFR C677T polymorphism and variable number tandem repeat 2R/3R and single nucleotide polymorphism G>C in the 3R allele of the TYMS gene with lung adenocarcinoma.",
+ "publisher": "Iranian journal of basic medical sciences",
+ "issn": "2008-3866",
+ "date": "2012-03-01",
+ "abstract": "Varicocele is associated with impaired testicular function and male infertility, but the molecular mechanisms by which fertility is affected have not been satisfactorily explained. The aim of our study was to investigate whether or not the polymerase gamma (POLG) polymorphism is associated with Iranian varicocele patients.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25536611"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23493802"
},
{
- "id": "pmid:25366766",
+ "id": "pmid:20937954",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25366766",
- "title": "Association between polymorphisms in the thymidylate synthase gene and risk of breast cancer in a Mexican population.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/20937954",
+ "title": "Mapping of autosomal dominant cerebellar ataxia without the pathogenic PPP2R2B mutation to the locus for spinocerebellar ataxia 12.",
"type": "article-journal",
- "doi": "10.4238/2014.october.27.16",
+ "doi": "10.1001/archneurol.2010.231",
"authors": [
- ["A", "Quintero-Ramos"],
- ["S A", "Guti\u00e9rrez-Rubio"],
- ["A", "Del Toro-Arreola"],
- ["R A", "Franco-Topete"],
- ["A", "Oceguera-Villanueva"],
- ["L M", "Jim\u00e9nez-P\u00e9rez"],
- ["J M", "Castro-Cervantes"],
- ["A", "Barrag\u00e1n-Ruiz"],
- ["J G", "V\u00e1zquez-Camacho"],
- ["A", "Daneri-Navarro"]
+ ["Kazunori", "Sato"],
+ ["Ichiro", "Yabe"],
+ ["Yoko", "Fukuda"],
+ ["Hiroyuki", "Soma"],
+ ["Yasuo", "Nakahara"],
+ ["Shoji", "Tsuji"],
+ ["Hidenao", "Sasaki"]
],
- "publisher": "Genetics and molecular research : GMR",
- "issn": "1676-5680",
- "date": "2014-10-27",
- "abstract": "Breast cancer (BC) is the leading cause of cancer-related deaths among women in Mexico. Two single-nucleotide polymorphisms (SNPs) in the thymidylate synthase (TS) gene, the 28-base pair (bp) tandem repeat in the TS 5'-untranslated enhanced region (TSER) and the 6-bp insertion/deletion in the TS 3'-untranslated region (TS 3'-UTR), increase the rate of misincorporation of uridylate into DNA and may lead to chromosomal damage. We examined the association between these polymorphisms and BC risk in Mexican women according to menopause status. Mexican patients with initial BC diagnosis (N = 230) and 145 individuals from a reference general population group (RGP) were included. For statistical analysis, the BC group was divided into pre- and post-menopause groups (PRE and POST groups, respectively). We analyzed both TS polymorphisms (TSER and TS 3'-UTR) using polymerase chain reaction. Finetti analysis was used to evaluate inter-and intra-group differences. The results showed a high frequency for the 3R and ins6 alleles in the BC, RGP, PRE, and POST groups. No significant differences were observed for the TS and TSER genotype and allele frequency distributions between groups. We found that the TSER and TS 3'-UTR SNPs are not associated with BC risk in Mexican patients.",
+ "publisher": "Archives of neurology",
+ "issn": "1538-3687",
+ "date": "2010-10-01",
+ "abstract": "To map the disease locus and to identify a gene mutation in a Japanese family with autosomal dominant cerebellar ataxia.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25366766"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20937954"
},
{
- "id": "pmid:25294632",
+ "id": "pmid:12451210",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25294632",
- "title": "Phase II trial of carboplatin and pemetrexed as first-line chemotherapy for non-squamous non-small cell lung cancer, and correlation between the efficacy/toxicity and genetic polymorphisms associated with pemetrexed metabolism: Hokkaido Lung Cancer Clinical Study Group Trial (HOT) 0902.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/12451210",
+ "title": "Creutzfeldt-Jakob disease associated with a deletion of two repeats in the prion protein gene.",
"type": "article-journal",
- "doi": "10.1007/s00280-014-2589-3",
+ "doi": "10.1212/01.wnl.0000035533.86833.28",
"authors": [
- ["Kenya", "Kanazawa"],
- ["Hiroshi", "Yokouchi"],
- ["Xintao", "Wang"],
- ["Takashi", "Ishida"],
- ["Yuka", "Fujita"],
- ["Satoru", "Fujiuchi"],
- ["Toshiyuki", "Harada"],
- ["Masao", "Harada"],
- ["Kei", "Takamura"],
- ["Satoshi", "Oizumi"],
- ["Ichiro", "Kinoshita"],
- ["Yutaka", "Katsuura"],
- ["Osamu", "Honjo"],
- ["Tetsuya", "Kojima"],
- ["Hirotoshi", "Dosaka-Akita"],
- ["Hiroshi", "Isobe"],
- ["Mitsuru", "Munakata"],
- ["Masaharu", "Nishimura"]
+ ["S", "Capellari"],
+ ["P", "Parchi"],
+ ["B D", "Wolff"],
+ ["J", "Campbell"],
+ ["R", "Atkinson"],
+ ["D M", "Posey"],
+ ["R B", "Petersen"],
+ ["P", "Gambetti"]
],
- "publisher": "Cancer chemotherapy and pharmacology",
- "issn": "1432-0843",
- "date": "2014-10-08",
- "abstract": "This phase II study evaluated the response rate (RR) and safety of combination therapy with carboplatin (CBDCA) and pemetrexed (PEM) in Japanese patients with non-squamous non-small cell lung cancer (non-sq NSCLC). Further, the relationship between therapy efficacy/toxicity and genetic polymorphisms associated with PEM metabolism was analyzed.",
+ "publisher": "Neurology",
+ "issn": "0028-3878",
+ "date": "2002-11-26",
+ "abstract": "A two-octapeptide repeat deletion of the prion protein gene has been recently observed in a patient with a 2-year history of dementia and a clinical diagnosis of possible Creutzfeldt-Jakob disease (CJD). The authors report a similar deletion in a patient with a definitive diagnosis of CJD. Since the two-repeat deletion has not been observed in large, population-based studies, the two cases suggest that this deletion is a new pathogenic mutation associated with CJD.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25294632"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12451210"
},
{
- "id": "pmid:25258183",
+ "id": "pmid:11594924",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25258183",
- "title": "Variable number tandem repeats in dopamine receptor D4 in Tourette's syndrome.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/11594924",
+ "title": "Association of moderate polyglutamine tract expansions in the slow calcium-activated potassium channel type 3 with ataxia.",
"type": "article-journal",
- "doi": "10.1002/mds.26027",
+ "doi": "10.1001/archneur.58.10.1649",
"authors": [
- ["Shiguo", "Liu"],
- ["Jiajia", "Cui"],
- ["Xinhua", "Zhang"],
- ["Weifeng", "Wu"],
- ["Haitao", "Niu"],
- ["Xu", "Ma"],
- ["Hongmei", "Xu"],
- ["Mingji", "Yi"]
- ],
- "publisher": "Movement disorders : official journal of the Movement Disorder Society",
- "issn": "1531-8257",
- "date": "2014-09-25",
- "abstract": "We attempted to clarify the association between dopamine receptor D4 (DRD4) 48-bp variable number of tandem repeats (VNTR) polymorphism and Tourette's syndrome.",
+ ["K P", "Figueroa"],
+ ["P", "Chan"],
+ ["L", "Sch\u00f6ls"],
+ ["C", "Tanner"],
+ ["O", "Riess"],
+ ["S L", "Perlman"],
+ ["D H", "Geschwind"],
+ ["S M", "Pulst"]
+ ],
+ "publisher": "Archives of neurology",
+ "issn": "0003-9942",
+ "date": "2001-10-01",
+ "abstract": "The small-conductance calcium-activated potassium channel gene (hSKCa3) contains 2 CAG repeats, 1 of which is highly polymorphic. Although this repeat is not pathologically expanded in patients with schizophrenia, some studies have suggested an allelic association with schizophrenia. CAG expansions in other genes such as the alpha1 subunit of a brain-specific P/Q-type calcium channel gene cause spinocerebellar ataxia type 6, whereas the length of the CAG repeat in the RAI1 gene modifies the age of onset of spinocerebellar ataxia type 2.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25258183"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11594924"
},
{
- "id": "pmid:25028118",
+ "id": "pmid:40221271",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/25028118",
- "title": "Polymorphisms in TS, MTHFR and ERCC1 genes as predictive markers in first-line platinum and pemetrexed therapy in NSCLC patients.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/40221271",
+ "title": "Response to the letter to the editor submitted by Dr. Berciano regarding the article entitled: \"Spectrum disorder of RFC1 expansions/CANVAS: Clinical and electrophysiological characterization of a group of 31 patients.\" https://doi.org/10.1016/j.clinph.2024.12.007.",
"type": "article-journal",
- "doi": "10.1007/s00432-014-1756-6",
+ "doi": "10.1016/j.clinph.2025.03.036",
"authors": [
- ["Pawe\u0142", "Krawczyk"],
- ["Tomasz", "Kucharczyk"],
- ["Dariusz M", "Kowalski"],
- ["Tomasz", "Powr\u00f3zek"],
- ["Rodryg", "Ramlau"],
- ["Ewa", "Kalinka-Warzocha"],
- ["Kinga", "Winiarczyk"],
- ["Magdalena", "Knetki-Wr\u00f3blewska"],
- ["Kamila", "Wojas-Krawczyk"],
- ["Katarzyna", "Ka\u0142akucka"],
- ["Wojciech", "Dyszkiewicz"],
- ["Maciej", "Krzakowski"],
- ["Janusz", "Milanowski"]
+ ["Elena", "Lainez"],
+ ["Daniel", "Sanchez-Tejerina"],
+ ["Nuria", "Raguer"]
],
- "publisher": "Journal of cancer research and clinical oncology",
- "issn": "1432-1335",
- "date": "2014-07-16",
- "abstract": "We presented retrospective analysis of up to five polymorphisms in TS, MTHFR and ERCC1 genes as molecular predictive markers for homogeneous Caucasian, non-squamous NSCLC patients treated with pemetrexed and platinum front-line chemotherapy.",
+ "publisher": "Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology",
+ "issn": "1872-8952",
+ "date": "2025-04-05",
+ "abstract": "",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:25028118"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40221271"
},
{
- "id": "pmid:24726028",
+ "id": "pmid:39231235",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/24726028",
- "title": "Thymidylate synthase polymorphisms in genomic DNA as clinical outcome predictors in a European population of advanced non-small cell lung cancer patients receiving pemetrexed.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/39231235",
+ "title": "AAGGG repeat expansions trigger",
"type": "article-journal",
- "doi": "10.1186/1479-5876-12-98",
+ "doi": "10.1126/sciadv.adn2321",
"authors": [
- ["Estefan\u00eda", "Ar\u00e9valo"],
- ["Eduardo", "Casta\u00f1\u00f3n"],
- ["In\u00e9s", "L\u00f3pez"],
- ["Josefa", "Salgado"],
- ["V\u00edctor", "Collado"],
- ["Marta", "Santisteban"],
- ["Mar\u00eda", "Rodr\u00edguez-Ruiz"],
- ["Patricia", "Mart\u00edn"],
- ["Leire", "Zubiri"],
- ["Ana", "Pati\u00f1o-Garc\u00eda"],
- ["Christian", "Rolfo"],
- ["Ignacio", "Gil-Bazo"]
+ ["Connor J", "Maltby"],
+ ["Amy", "Krans"],
+ ["Samantha J", "Grudzien"],
+ ["Yomira", "Palacios"],
+ ["Jessica", "Mui\u00f1os"],
+ ["Andrea", "Su\u00e1rez"],
+ ["Melissa", "Asher"],
+ ["Sydney", "Willey"],
+ ["Kinsey", "Van Deynze"],
+ ["Camille", "Mumm"],
+ ["Alan P", "Boyle"],
+ ["Andrea", "Cortese"],
+ ["Alain", "Ndayisaba"],
+ ["Vikram", "Khurana"],
+ ["Sami J", "Barmada"],
+ ["Anke A", "Dijkstra"],
+ ["Peter K", "Todd"]
],
- "publisher": "Journal of translational medicine",
- "issn": "1479-5876",
- "date": "2014-04-14",
- "abstract": "We studied whether thymidylate synthase (TS) genotype has an independent prognostic/predictive impact on a European population of advanced non-small cell lung cancer (NSCLC) patients receiving pemetrexed.",
+ "publisher": "Science advances",
+ "issn": "2375-2548",
+ "date": "2024-09-04",
+ "abstract": "Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a recessively inherited neurodegenerative disorder caused by intronic biallelic, nonreference CCCTT/AAGGG repeat expansions within",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24726028"
-},
-{
- "id": "pmid:24596472",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/24596472",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:24596472']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39231235"
},
{
- "id": "pmid:24554028",
+ "id": "pmid:38266156",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/24554028",
- "title": "Thymidylate synthase polymorphisms are associated to therapeutic outcome of advanced non-small cell lung cancer patients treated with platinum-based chemotherapy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38266156",
+ "title": "Structural investigation of pathogenic RFC1 AAGGG pentanucleotide repeats reveals a role of G-quadruplex in dysregulated gene expression in CANVAS.",
"type": "article-journal",
- "doi": "10.1007/s11033-014-3197-3",
+ "doi": "10.1093/nar/gkae032",
"authors": [
- ["Aurea", "Lima"],
- ["V\u00edtor", "Seabra"],
- ["Sandra", "Martins"],
- ["Ana", "Coelho"],
- ["Ant\u00f3nio", "Ara\u00fajo"],
- ["Rui", "Medeiros"]
+ ["Yang", "Wang"],
+ ["Junyan", "Wang"],
+ ["Zhenzhen", "Yan"],
+ ["Jianing", "Hou"],
+ ["Liqi", "Wan"],
+ ["Yingquan", "Yang"],
+ ["Yu", "Liu"],
+ ["Jie", "Yi"],
+ ["Pei", "Guo"],
+ ["Da", "Han"]
],
- "publisher": "Molecular biology reports",
- "issn": "1573-4978",
- "date": "2014-02-20",
- "abstract": "Thymidylate synthase (TYMS) has three polymorphisms that may modulate thymidylate synthase (TS) expression levels: (1) 28 base pairs (bp) variable number tandem repeat (VNTR) (rs34743033); (2) single nucleotide polymorphism (SNP) C>G at the twelfth nucleotide of the second repeat of 3R allele (rs2853542); and (3) 6 bp sequence deletion (1494del6, rs34489327). This study was conducted to evaluate the influence of TYMS polymorphisms on the survival of Portuguese patients with advanced non-small cell lung cancer (NSCLC) undergoing platinum-based chemotherapy. Our results showed no statistically significant differences between VNTR genotypes; although, considering the SNP C>G, homozygotes 3RG presented a better prognostic at 36 months (p=0.004) and overall survival (p=0.003) when compared to 2R3RG patients. Patients with \"median/high expression genotypes\" demonstrated a better survival at 12 months (p=0.041) when compared to \"low expression genotypes\". Furthermore, 6 bp- carriers (p=0.006) showed a better survival at 12 months when compared to 6 bp+ homozygotes patients. When analyzing TYMS haplotypes, better survival at 12 months was observed for patients carrying haplotypes with the 6 bp- allele (2R6 bp-; p=0.026 and 3RG6 bp-; p=0.045). This is the first report that evaluates the three major TYMS polymorphisms in the therapeutic outcome of NSCLC in Portugal. According to our results, the TYMS polymorphisms may be useful tools to predict which advanced NSCLC patients could benefit more from platinum-based chemotherapy regimens.",
+ "publisher": "Nucleic acids research",
+ "issn": "1362-4962",
+ "date": "2024-03-21",
+ "abstract": "An expansion of AAGGG pentanucleotide repeats in the replication factor C subunit 1 (RFC1) gene is the genetic cause of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), and it also links to several other neurodegenerative diseases including the Parkinson's disease. However, the pathogenic mechanism of RFC1 AAGGG repeat expansion remains enigmatic. Here, we report that the pathogenic RFC1 AAGGG repeats form DNA and RNA parallel G-quadruplex (G4) structures that play a role in impairing biological processes. We determine the first high-resolution nuclear magnetic resonance (NMR) structure of a bimolecular parallel G4 formed by d(AAGGG)2AA and reveal how AAGGG repeats fold into a higher-order structure composed of three G-tetrad layers, and further demonstrate the formation of intramolecular G4s in longer DNA and RNA repeats. The pathogenic AAGGG repeats, but not the nonpathogenic AAAAG repeats, form G4 structures to stall DNA replication and reduce gene expression via impairing the translation process in a repeat-length-dependent manner. Our results provide an unprecedented structural basis for understanding the pathogenic mechanism of AAGGG repeat expansion associated with CANVAS. In addition, the high-resolution structures resolved in this study will facilitate rational design of small-molecule ligands and helicases targeting G4s formed by AAGGG repeats for therapeutic interventions.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24554028"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38266156"
},
{
- "id": "pmid:24137384",
+ "id": "pmid:37747091",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/24137384",
- "title": "Polymorphisms of",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/37747091",
+ "title": "Pseudo-eye-of-the-tiger sign in cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS).",
"type": "article-journal",
- "doi": "10.3892/ol.2013.1467",
+ "doi": "10.1002/ajmg.a.63419",
"authors": [
- ["Kensuke", "Kumamoto"],
- ["Keiichiro", "Ishibashi"],
- ["Norimichi", "Okada"],
- ["Yusuke", "Tajima"],
- ["Kouki", "Kuwabara"],
- ["Yoichi", "Kumagai"],
- ["Hiroyuki", "Baba"],
- ["Norihiro", "Haga"],
- ["Hideyuki", "Ishida"]
+ ["Vasco Sousa", "Abreu"],
+ ["Jos\u00e9 S\u00e1", "Silva"],
+ ["Liliana", "Igreja"],
+ ["Maria Jo\u00e3o", "Malaquias"],
+ ["Catarina Mendes", "Pinto"]
],
- "publisher": "Oncology letters",
- "issn": "1792-1074",
- "date": "2013-07-15",
- "abstract": "The aim of the current study was to examine whether polymorphisms in drug metabolism genes have any clinical impact on patients treated with 5-fluorouracil (FU)/oxaliplatin for metastatic colorectal cancer (MCRC). In total, 63 patients with MCRC were recruited and treated with a modified FOLFOX6 (mFOLFOX6) treatment as a first-line chemotherapy. Polymorphisms in five drug metabolism genes and two DNA-repair genes were assessed in these patients using polymerase chain reaction (PCR), a PCR restriction fragment length polymorphism (PCR-RFLP) technique or invader techniques. These included a 28-bp tandem repeat in the 5'-untranslated region (UTR) and 6-bp deletions in the 3'-UTR of thymidylate synthase (",
+ "publisher": "American journal of medical genetics. Part A",
+ "issn": "1552-4833",
+ "date": "2023-09-25",
+ "abstract": "The well-known eye-of-the-tiger sign features bilateral and symmetrical changes in the globus pallidus, with a central area of high signal and peripheral low signal on T2-weighted MRI. Although formally considered pathognomonic of pantothenate kinase-associated neurodegeneration (PKAN), there are other neurodegenerative or genetic diseases showing similar findings. Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a late-onset ataxia, that was recently associated with biallelic AAGGG repeat expansion in the RFC1 gene. Although its predominant MRI finding is cerebellar atrophy, there may be other less common associated findings. Our aim is to present two cases of CANVAS with associated (pseudo-)eye-of-the-tiger sign, highlighting the possibility of yet another differential diagnosis for this imaging sign.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24137384"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:37747091"
},
{
- "id": "pmid:23968134",
+ "id": "pmid:36381255",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23968134",
- "title": "Thymidylate synthase gene polymorphism and survival of colorectal cancer patients receiving adjuvant 5-fluorouracil.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/36381255",
+ "title": "Cognitive Impairment in a Complex Family With AAGGG and ACAGG Repeat Expansions in RFC1 Detected by ExpansionHunter Denovo.",
"type": "article-journal",
- "doi": "10.1089/gtmb.2013.0171",
+ "doi": "10.1212/nxg.0000000000000682",
"authors": [
- ["Violetta", "Sulzyc-Bielicka"],
- ["Dariusz", "Bielicki"],
- ["Agnieszka", "Binczak-Kuleta"],
- ["Mariusz", "Kaczmarczyk"],
- ["Wies\u0142awa", "Pioch"],
- ["Anna", "Machoy-Mokrzynska"],
- ["Andrzej", "Ciechanowicz"],
- ["Magdalena", "Go\u0142\u0119biewska"],
- ["Marek", "Drozdzik"]
+ ["Kazuki", "Watanabe"],
+ ["Mitsuko", "Nakashima"],
+ ["Rie", "Wakatsuki"],
+ ["Tomoyasu", "Bunai"],
+ ["Yasuomi", "Ouchi"],
+ ["Tomohiko", "Nakamura"],
+ ["Hiroaki", "Miyajima"],
+ ["Hirotomo", "Saitsu"]
],
- "publisher": "Genetic testing and molecular biomarkers",
- "issn": "1945-0257",
- "date": "2013-08-22",
- "abstract": "Limited studies indicate a possible association of 5'-UTR thymidylate synthase enhancer region polymorphism and treatment outcome in patients medicated with 5-fluorouracil (5-FU). The study was designed to verify the relationship in patients with colorectal cancer (CRC), a Polish population that received 5-FU-based adjuvant chemotherapy. The study analyzed 145 Astler-Coller B2 and C CRC patients. Genotyping for a variable number of tandem repeats and G to C single-nucleotide polymorphism in the 5'-UTR of the thymidylate synthase (TS) gene was carried out. TS genotypes were classified into high expression (high TS) and low expression types (low TS). High TS was found in 22.8% of patients. The right-side tumors were more frequently associated with high TS than the left-side tumors (p=0.024). High TS was only found in 9.3% of rectal tumors, but in 29.7% of colon cancers (p=0.0042). Disease-free survival after 20 months (DFS 20) was longer in subjects with low TS than in high TS (p=0.043). Patients who underwent chemotherapy had longer DFS 20 in the low TS than in the high TS subgroup (p=0.051). The low TS was found to be an independent good prognostic factor for DFS 20 in the whole group as well as in the subgroup treated with chemotherapy (p=0.024 and p=0.034, respectively). Patients with low TS did not show any differences in DFS 20 whether they were treated with adjuvant chemotherapy or not. Proximal CRC tumors are characterized by higher TS expression genotypes than distal tumors, and are at significantly greater risk of early recurrence during the first 20 months after surgery.",
+ "publisher": "Neurology. Genetics",
+ "issn": "2376-7839",
+ "date": "2022-05-16",
+ "abstract": "We investigated the genetic basis and brain metabolism and blood flow of a Japanese family with spinocerebellar degeneration (SCD), with multiple affected members for 3 generations.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23968134"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:36381255"
},
{
- "id": "pmid:23481061",
+ "id": "pmid:35013364",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23481061",
- "title": "Genetic variability & chemotoxicity of 5-fluorouracil & cisplatin in head & neck cancer patients: a preliminary study.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/35013364",
+ "title": "Biallelic expansion in RFC1 as a rare cause of Parkinson's disease.",
"type": "article-journal",
- "doi": "",
+ "doi": "10.1038/s41531-021-00275-7",
"authors": [
- ["Dipali", "Dhawan"],
- ["Harsha", "Panchal"],
- ["Shilin", "Shukla"],
- ["Harish", "Padh"]
+ ["Laura", "Kyt\u00f6vuori"],
+ ["Jussi", "Sipil\u00e4"],
+ ["Hiroshi", "Doi"],
+ ["Anri", "Hurme-Niiranen"],
+ ["Ari", "Siitonen"],
+ ["Eriko", "Koshimizu"],
+ ["Satoko", "Miyatake"],
+ ["Naomichi", "Matsumoto"],
+ ["Fumiaki", "Tanaka"],
+ ["Kari", "Majamaa"]
],
- "publisher": "The Indian journal of medical research",
- "issn": "0975-9174",
- "date": "2013-01-01",
- "abstract": "background & objectives: The efficacy and toxicity of a given chemotherapy regimen varies widely among patients due to the inherited variability of genes that are involved in drug metabolism. There are several crucial enzymes identified involving metabolism of 5-fluorouracil (5-FU) and cisplatin, which are polymorphic. We studied head and neck cancer patients (n=23) on 5-FU and cisplatin combination therapy attending a tertiary care cancer research institute in Gujarat, India, to understand the effect of a particular genotype on toxicity.",
+ "publisher": "NPJ Parkinson's disease",
+ "issn": "2373-8057",
+ "date": "2022-01-10",
+ "abstract": "An intronic expansion (AAGGG)",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23481061"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:35013364"
},
{
- "id": "pmid:23226765",
+ "id": "pmid:31370354",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/23226765",
- "title": "Correlation between thymidylate synthase gene polymorphisms and efficacy of pemetrexed in advanced non-small cell lung cancer.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/31370354",
+ "title": "Association of Polymorphisms in Genes Involved in One-Carbon Metabolism with",
"type": "article-journal",
- "doi": "10.3892/etm.2012.730",
+ "doi": "10.3390/ijms20153754",
"authors": [
- ["Qiong", "Hu"],
- ["Xuefei", "Li"],
- ["Chunxia", "Su"],
- ["Xiaoxia", "Chen"],
- ["Guanghui", "Gao"],
- ["Jie", "Zhang"],
- ["Yinmin", "Zhao"],
- ["Jiayu", "Li"],
- ["Caicun", "Zhou"]
+ ["Fabio", "Copped\u00e8"],
+ ["Andrea", "Stoccoro"],
+ ["Pierpaola", "Tannorella"],
+ ["Roberta", "Gallo"],
+ ["Vanessa", "Nicol\u00ec"],
+ ["Lucia", "Migliore"]
],
- "publisher": "Experimental and therapeutic medicine",
- "issn": "1792-0981",
- "date": "2012-09-28",
- "abstract": "One of the target genes of pemetrexed (PEM), thymidylate synthase (TS), has been shown to have a close association with its efficacy. TS gene polymorphisms have been shown to be associated with the efficacy of antifolate treatment in enteron tumors. The purpose of this study was to investigate the clinical significance of TS gene polymorphisms in patients with advanced NSCLC receiving PEM-based treatment. The variable nucleoid tandem repeat in the 5'-UTR region was amplified and detected using fluorescently labeled multiplex short tandem repeat polymerase chain reaction. The polymorphism in the 3'-UTR region of the TS gene was detected using the Taqman probe. Efficacy of PEM was assessed according to the Response Evaluation Criteria in Solid Tumors, version 1.1. None of the genotypes were associated with gender, smoking status and age. Disease control rate (DCR), objective response rate (ORR) and progression-free survival (PFS) were similar between patients harboring 2R and 3R alleles (PFS, p=0.518; DCR, p=0.631; ORR, p=0.541), as well as those with a 6-bp insertion and 6-bp deletion (PFS, p=0.776; DCR, p=0.626; ORR, p=0.330). To study the combined effect of TS polymorphisms, the study population was divided into three groups: 2R&6 del, 2R&6 ins and 3R&6 del. No significant differences were observed among the different groups according to DCR (p=0.517), ORR (p=0.611) and PFS (p=0.938). In conclusion, polymorphisms of the TS gene do not appear to be a prognostic marker for advanced NSCLC patients receiving PEM-based treatment.",
+ "publisher": "International journal of molecular sciences",
+ "issn": "1422-0067",
+ "date": "2019-07-31",
+ "abstract": "Methylenetetrahydrofolate reductase (MTHFR) is a pivotal enzyme in the one-carbon metabolism, a metabolic pathway required for DNA synthesis and methylation reactions.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:23226765"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:31370354"
},
{
- "id": "pmid:22576918",
+ "id": "pmid:32174879",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/22576918",
- "title": "Thymidylate synthase enhancer region polymorphism not related to susceptibility to acute lymphoblastic leukemia in the Kashmir population.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/32174879",
+ "title": "TTTCA Repeat Expansion of",
"type": "article-journal",
- "doi": "10.4238/2012.april.10.6",
+ "doi": "10.3389/fneur.2020.00068",
"authors": [
- ["F H", "Nazki"],
- ["A", "Masood"],
- ["M A", "Banday"],
- ["A", "Bhat"],
- ["B A", "Ganai"]
+ ["Chaorong", "Liu"],
+ ["Yanmin", "Song"],
+ ["Ying", "Yuan"],
+ ["Ying", "Peng"],
+ ["Nan", "Pang"],
+ ["Ranhui", "Duan"],
+ ["Wen", "Huang"],
+ ["Xuehui", "Qin"],
+ ["Wenbiao", "Xiao"],
+ ["Hongyu", "Long"],
+ ["Sha", "Huang"],
+ ["Pinting", "Zhou"],
+ ["Lili", "Long"],
+ ["Bo", "Xiao"]
],
- "publisher": "Genetics and molecular research : GMR",
- "issn": "1676-5680",
- "date": "2012-04-10",
- "abstract": "Thymidylate synthase (TS) is a crucial enzyme in folate metabolism and plays a vital role in DNA synthesis and repair. The most common polymorphism in TS is a unique double (2R) or triple (3R) 28-bp tandem repeat sequence in the enhancer region of the TS gene (TSER). This genetic variation in TSER has been widely investigated and has been implicated as a risk factor for the development of various cancers, including acute lymphoblastic leukemia. It has also been found to influence sensitivity to anti-cancer drugs, such as methotrexate. We evaluated this polymorphism in acute lymphoblastic leukemia patients in the Kashmir population. In order to determine whether a double (2R2R) versus a triple (3R3R) 28-bp tandem repeat in the TSER modulates risk for acute lymphoblastic leukemia, 72 acute lymphoblastic leukemia cases and 144 age and gender matched, unrelated healthy individuals from the Kashmir region of India were evaluated for this polymorphism by PCR and direct sequencing. We found the frequency of the TS 2R allele to be 32.6 and 26.0%, in cases and controls, respectively. The TS 2R/2R genotype was found to be present in 15.27% of the cases and 9.72% of the controls, the 2R/3R variant in 34.72% of the cases and 32.63% of the controls, and the 3R/3R genotype in 50.0% of the cases and 57.63% of the controls. There was a significant association between the TS 2R/2R genotype and gender of acute lymphoblastic leukemia patients with males harboring the 2R/2R genotype exhibiting a higher risk of developing acute lymphoblastic leukemia than females (P = 0.009) We concluded that the TSER polymorphism appears not to be a risk factor for susceptibility to acute lymphoblastic leukemia in the Kashmir population.",
+ "publisher": "Frontiers in neurology",
+ "issn": "1664-2295",
+ "date": "2020-02-26",
+ "abstract": "Benign adult familial myoclonic epilepsy (BAFME) is an autosomal dominant disorder characterized by adult-onset cortical myoclonus with or without seizures. Recently, it was reported to be associated with intronic TTTTA/TTTCA expansions. To investigate whether these abnormal expansions are involved in our new pedigree from China, whole exome sequencing (WES) and repeat-primed polymerase chain reaction (RP-PCR) analysis were performed to detect potential mutation in pedigree members. Neither causal mutations cosegregated with the disease in the family nor any novel mutation was identified through WES, while an abnormal TTTCA expansion in",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22576918"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32174879"
},
{
- "id": "pmid:22044939",
+ "id": "pmid:32152096",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/22044939",
- "title": "Impact of SHMT1 polymorphism on the clinical outcome of patients with metastatic colorectal cancer treated with first-line FOLFIRI+bevacizumab.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/32152096",
+ "title": "Correction for Cristopher Bragg et al., Disease onset in X-linked dystonia-parkinsonism correlates with expansion of a hexameric repeat within an SVA retrotransposon in",
"type": "article-journal",
- "doi": "10.1097/fpc.0b013e32834d8376",
+ "doi": "10.1073/pnas.2003190117",
+ "authors": [],
+ "publisher": "Proceedings of the National Academy of Sciences of the United States of America",
+ "issn": "1091-6490",
+ "date": "2020-03-09",
+ "abstract": "",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:32152096"
+},
+{
+ "id": "pmid:38494459",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/38494459",
+ "title": "Cognitive dysfunction, social behavior disorder, cerebellar ataxia, and atypical brain FDG-PET presentation in spinocerebellar ataxia 17: a case report.",
+ "type": "article-journal",
+ "doi": "10.1007/s10072-024-07453-4",
"authors": [
- ["Barna", "Budai"],
- ["Viktor", "Koml\u00f3si"],
- ["Vilmos", "Adleff"],
- ["\u00c9va", "Pap"],
- ["Andrea", "R\u00e9ti"],
- ["T\u00fcnde", "Nagy"],
- ["Judit", "Kralov\u00e1nszky"],
- ["Istv\u00e1n", "L\u00e1ng"],
- ["Erika", "Hitre"]
+ ["Alberto", "Grassini"],
+ ["Aurora", "Cermelli"],
+ ["Fausto", "Roveta"],
+ ["Michela", "Zotta"],
+ ["Adriana", "Lesca"],
+ ["Andrea", "Marcinn\u00f2"],
+ ["Fabio", "Ferrandes"],
+ ["Elisa", "Piella"],
+ ["Silvia", "Boschi"],
+ ["Chiara", "Lombardo"],
+ ["Alfredo", "Brusco"],
+ ["Salvatore", "Gallone"],
+ ["Elisa", "Rubino"],
+ ["Amalia", "Bruni"],
+ ["Innocenzo", "Rainero"]
],
- "publisher": "Pharmacogenetics and genomics",
- "issn": "1744-6880",
- "date": "2012-01-01",
- "abstract": "The impact of thymidylate synthase (TYMS), methylenetetrahydrofolate reductase (MTHFR), and serine hydroxymethyltransferase 1 (SHMT1) gene polymorphisms and that of dihydropyrimidine dehydrogenase (DPD) enzyme activity, serum total homocysteine level, and estimated serum creatinine clearance on first-line 5-fluorouracil, leucovorin, irinotecan, and bevacizumab (FOLFIRI+bevacizumab) regimen efficacy in metastatic colorectal cancer patients was investigated. DNA was extracted from peripheral blood mononuclear cells. Genotyping was performed for TYMS 5'UTR variable number tandem repeat, TYMS 3'UTR ins/del, MTHFR C677T, and SHMT1 C1420T polymorphisms. The DPD activity of peripheral blood mononuclear cells was also determined. The univariate and multivariate analyses demonstrated that the SHMT1 1420T allele was associated with better response (P=0.025) and longer progression-free survival (PFS) (P=0.00004) and overall survival (OS) (P=0.034). Grade \u22652 hypertension was also an independent prognostic factor of longer progression-free survival and OS. Bevacizumab-related hypertension might be a predictive marker of treatment efficacy (P=0.0002 for OS) in the case of wild (CC) SHMT1 1420 genotypes only.",
+ "publisher": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology",
+ "issn": "1590-3478",
+ "date": "2024-03-18",
+ "abstract": "Spinocerebellar ataxia 17 (SCA17) is a rare autosomal dominant form of inherited ataxia, caused by heterozygous trinucleotide repeat expansions encoding glutamine in the TATA box-binding protein (TBP) gene.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:22044939"
-},
-{
- "id": "pmid:21449681",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/21449681",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:21449681']' timed out after 3 seconds"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38494459"
},
{
- "id": "pmid:21196216",
+ "id": "pmid:28821675",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/21196216",
- "title": "TS gene tandem repeats in esophageal cancer patients receiving chemoradiotherapy.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/28821675",
+ "title": "Synergistic Toxicity of Polyglutamine-Expanded TATA-Binding Protein in Glia and Neuronal Cells: Therapeutic Implications for Spinocerebellar Ataxia 17.",
"type": "article-journal",
- "doi": "10.2741/3733",
+ "doi": "10.1523/jneurosci.0111-17.2017",
"authors": [
- ["Kazuhiro", "Kaneko"],
- ["Maho", "Nagai"],
- ["Yoshitaka", "Murakami"],
- ["Mari", "Kogo"],
- ["Tsunehiro", "Oyama"],
- ["Takashi", "Kojima"],
- ["Atsushi", "Ohtsu"],
- ["Michio", "Imawari"]
+ ["Yang", "Yang"],
+ ["Su", "Yang"],
+ ["Jifeng", "Guo"],
+ ["Yiting", "Cui"],
+ ["Beisha", "Tang"],
+ ["Xiao-Jiang", "Li"],
+ ["Shihua", "Li"]
],
- "publisher": "Frontiers in bioscience (Landmark edition)",
- "issn": "2768-6698",
- "date": "2011-01-01",
- "abstract": "5-Fluorouracil (5-FU) interferes with tumor-cell proliferation by inhibiting thymidylate synthase (TS). We examined the relationship between tandem repeat (TR) variations in the TS gene and survival following concurrent chemoradiotherapy in patients with esophageal squamous cell carcinoma (ESCC). TS-TR variations were analyzed in 57 stage II-IV ESCC patients undergoing chemoradiotherapy combined with 5-FU and cisplatinum (CDDP), and in 106 controls. Pretreatment non-neoplastic biopsy specimens from ESCC patients and lymphocytes from controls were used for analysis. Variations were identified by the size of DNA fragments amplified by polymerase chain reaction. Two to five TRs were found in Japanese individuals. TR3 homozygotes were predominant in 74% of ESCC patients and 61% of controls. Three-year survival rates were significantly longer in patients with TR2/2 or TR2/3 genotypes (38%) than in patients with TR3/3, 3/4, or 3/5 genotypes (9%; p=0.011). In the Cox proportional hazard model, the TR2/2 or TR2/3 genotypes were the only independent predictor for survival (Hazard ratio, 2.647; 95% confidence interval, 1.271-5.513). The TS-TR variations exert an important influence on survival following chemoradiotherapy in ESCC patients.",
+ "publisher": "The Journal of neuroscience : the official journal of the Society for Neuroscience",
+ "issn": "1529-2401",
+ "date": "2017-08-18",
+ "abstract": "Spinocerebellar ataxia 17 (SCA17) is caused by polyglutamine (polyQ) repeat expansion in the TATA-binding protein (TBP) and is among a family of neurodegenerative diseases in which polyQ expansion leads to preferential neuronal loss in the brain. Although previous studies have demonstrated that expression of polyQ-expanded proteins in glial cells can cause neuronal injury via noncell-autonomous mechanisms, these studies investigated animal models that overexpress transgenic mutant proteins. Since glial cells are particularly reactive to overexpressed mutant proteins, it is important to investigate the",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21196216"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:28821675"
},
{
- "id": "pmid:20932673",
+ "id": "pmid:21710129",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/20932673",
- "title": "Thymidylate synthase gene polymorphism affects the response to preoperative 5-fluorouracil chemoradiation therapy in patients with rectal cancer.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21710129",
+ "title": "Early-onset SCA17 with 43 TBP repeats: expanding the phenotype?",
"type": "article-journal",
- "doi": "10.1016/j.ijrobp.2010.06.049",
+ "doi": "10.1007/s10072-011-0662-9",
"authors": [
- ["Hyuk", "Hur"],
- ["Jeonghyun", "Kang"],
- ["Nam Kyu", "Kim"],
- ["Byung Soh", "Min"],
- ["Kang Young", "Lee"],
- ["Sang Joon", "Shin"],
- ["Ki Chang", "Keum"],
- ["Junjeong", "Choi"],
- ["Hoguen", "Kim"],
- ["Sung Ho", "Choi"],
- ["Mi-Young", "Lee"]
+ ["L", "Tremolizzo"],
+ ["N A", "Curt\u00f2"],
+ ["L", "Marzorati"],
+ ["F", "Lanzani"],
+ ["P", "Tarantino"],
+ ["G", "Annesi"],
+ ["C", "Ferrarese"]
],
- "publisher": "International journal of radiation oncology, biology, physics",
- "issn": "1879-355X",
- "date": "2010-10-06",
- "abstract": "This study aims to correlate thymidylate synthase (TS) gene polymorphisms with the tumor response to preoperative 5-fluorouracil (5-FU)-based chemoradiation therapy (CRT) in patients with rectal cancer.",
+ "publisher": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology",
+ "issn": "1590-3478",
+ "date": "2011-06-28",
+ "abstract": "The SCA17 clinical phenotype includes characteristics associated with cerebellar and cortical atrophy such as ataxia, dementia, epilepsy, chorea and parkinsonian features. Here we describe the case of a 38-year-old male presenting with ataxia, cognitive impairment and seizures, who was found to carry 43 repeats on one allele of the TATA-binding protein (TBP) gene. Therefore, genetic analysis of TBP gene triplets was performed on the patient's entire family, identifying three asymptomatic carriers of the same allele. A neuroradiological phenotype appeared to segregate with this allele, suggesting that it may play at least a contributory role in the determination of SCA17.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20932673"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21710129"
},
{
- "id": "pmid:20880668",
+ "id": "pmid:17033685",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/20880668",
- "title": "Dyssynchronous systolic expansion of carotid artery in patients with marfan syndrome.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/17033685",
+ "title": "Repeat expansion in spinocerebellar ataxia type 17 alleles of the TATA-box binding protein gene: an evolutionary approach.",
"type": "article-journal",
- "doi": "10.1016/j.echo.2010.08.022",
+ "doi": "10.1038/sj.ejhg.5201721",
"authors": [
- ["Woo-In", "Yang"],
- ["Chi-Young", "Shim"],
- ["In-Jeong", "Cho"],
- ["Hyuk-Jae", "Chang"],
- ["Donghoon", "Choi"],
- ["Yangsoo", "Jang"],
- ["Namsik", "Chung"],
- ["Seung-Yun", "Cho"],
- ["Jong-Won", "Ha"]
+ ["J\u00fcrgen", "Tomiuk"],
+ ["Lutz", "Bachmann"],
+ ["Claudia", "Bauer"],
+ ["Arndt", "Rolfs"],
+ ["Ludger", "Sch\u00f6ls"],
+ ["Christian", "Roos"],
+ ["Hans", "Zischler"],
+ ["Mathias M", "Schuler"],
+ ["Silke", "Bruntner"],
+ ["Olaf", "Riess"],
+ ["Peter", "Bauer"]
],
- "publisher": "Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography",
- "issn": "1097-6795",
- "date": "2010-09-29",
- "abstract": "Marfan syndrome is a multisystemic connective tissue disorder associated with a mutation affecting fibrillin-1, the main component of microfibrils. Fibrillin-1 gene mutations may affect the carotid arterial wall. The aim of this study was to investigate carotid arterial mechanics using Velocity Vector Imaging (VVI) in patients with Marfan syndrome.",
+ "publisher": "European journal of human genetics : EJHG",
+ "issn": "1018-4813",
+ "date": "2006-10-11",
+ "abstract": "The variability and mutational changes of the CAG microsatellite in the TATA-box binding protein gene (TBP) were studied. We sequenced the microsatellite of the TBP gene of 25 unrelated individuals from northern Germany (10 SCA17 patients and 15 unaffected control individuals). In addition, the microsatellites were sequenced from individuals of 10 northern German families with at least one family member affected by SCA17. To study also the evolutionary history of this CAG/CAA microsatellite in nonhuman primates, the homologous regions were analysed from Pan troglodytes, Gorilla gorilla, Pongo pygmaeus, P. abellii, Hylobates lar, Nomascus leucogenys, Symphalangus syndactylus, Macaca mulatta, Papio hamadryas, Colobus polykomos and Callithrix jacchus. Three major conclusions were drawn: (i) Patterns of synonymous CAA interruptions in the microsatellite are characteristic and likely to result from selection for stabilizing the repetitive region; (ii) Interspecific comparisons indicate that SCA17 is likely to be a human trait. The most common allele in humans (37 repeats) is close to the threshold value upon which neurodegenerative changes can occur and may act as a repository for expanded, pathogenic alleles; (iii) The cassette-like structure of five out of 17 expanded alleles can be attributed to unequal crossing over. This can explain the rare and sporadic de novo generation of SCA17 alleles.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20880668"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17033685"
},
{
- "id": "pmid:20651387",
+ "id": "pmid:12758065",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/20651387",
- "title": "Polymorphisms of thymidylate synthase gene 5'- and 3'-untranslated region and risk of gastric cancer in Koreans.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/12758065",
+ "title": "Molecular investigation of TBP allele length: a SCA17 cellular model and population study.",
"type": "article-journal",
- "doi": "",
+ "doi": "10.1016/s0969-9961(03)00014-7",
"authors": [
- ["Dong Jin", "Yim"],
- ["Ok Jun", "Kim"],
- ["Hee Jung", "An"],
- ["Haeyoun", "Kang"],
- ["Dae Ho", "Ahn"],
- ["Seong Gyu", "Hwang"],
- ["Doyeun", "Oh"],
- ["Nam Keun", "Kim"]
+ ["Suzanne J", "Reid"],
+ ["Mark I", "Rees"],
+ ["Willeke M C", "van Roon-Mom"],
+ ["A Lesley", "Jones"],
+ ["Marcy E", "MacDonald"],
+ ["Greg", "Sutherland"],
+ ["Matthew J", "During"],
+ ["Richard L M", "Faull"],
+ ["Michael J", "Owen"],
+ ["Mike", "Dragunow"],
+ ["Russell G", "Snell"]
],
- "publisher": "Anticancer research",
- "issn": "1791-7530",
- "date": "2010-06-01",
- "abstract": "Thymidylate synthase (TS) plays an important role in the conversion of dUMP to dTMP. Polymorphisms of the TS gene affect the expression of the gene, which in turn may result in differences in the outcome of cancer chemotherapy and the progression of gastric cancer.",
+ "publisher": "Neurobiology of disease",
+ "issn": "0969-9961",
+ "date": "2003-06-01",
+ "abstract": "Recently, an inherited spinocerebellar ataxia (SCA17) has been attributed to polyglutamine coding expansions within the gene coding for human TATA-box binding protein (TBP). The normal repeat range is 25-42 units with patients having as few as 46 repeats. We undertook a TBP repeat length population study showing its relative stability, skewed distribution, and substantial population specific differences. To investigate the mechanism of neurodegeneration in SCA17 we have developed a cellular model expressing full-length TBP with a range of polyQ expansions. As has been found with other polyQ cellular models, insoluble intracellular inclusions form in a repeat-length-dependent manner. In addition, we have shown that the expanded TBP polyQ tract is able to interact with other overexpressed polyQ-containing proteins. Importantly, overexpression of expanded TBP results in increased Cre-dependent transcriptional activity. As TBP is required for transcription by all RNA polymerases, this may indicate a mechanism for aberrant polyQ gain of function.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20651387"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12758065"
},
{
- "id": "pmid:20372856",
+ "id": "pmid:39278108",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/20372856",
- "title": "Influence of thymidylate synthase DNA polymorphisms and gender on the clinical evolution of patients with advanced colorectal cancer.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/39278108",
+ "title": "Tissue-specific TCF4 triplet repeat instability revealed by optical genome mapping.",
"type": "article-journal",
- "doi": "10.3892/or_00000776",
+ "doi": "10.1016/j.ebiom.2024.105328",
"authors": [
- ["Maria-Encarnaci\u00f3n", "Fern\u00e1ndez-Contreras"],
- ["Jos\u00e9 Javier", "S\u00e1nchez-Hern\u00e1ndez"],
- ["Mercedes", "Guijarro"],
- ["Javier P", "Gisbert"],
- ["Noa", "Rivas"],
- ["Mar\u00eda-Luisa", "Garc\u00eda de Paredes"],
- ["Adolfo", "Hinojar-Guti\u00e9rrez"],
- ["Carlos", "Gamallo"]
+ ["Christina", "Zarouchlioti"],
+ ["Stephanie", "Efthymiou"],
+ ["Stefano", "Facchini"],
+ ["Natalia", "Dominik"],
+ ["Nihar", "Bhattacharyya"],
+ ["Siyin", "Liu"],
+ ["Marcos Abreu", "Costa"],
+ ["Anita", "Szabo"],
+ ["Amanda N", "Sadan"],
+ ["Albert S", "Jun"],
+ ["Enrico", "Bugiardini"],
+ ["Henry", "Houlden"],
+ ["Andrea", "Cortese"],
+ ["Pavlina", "Skalicka"],
+ ["Lubica", "Dudakova"],
+ ["Kirithika", "Muthusamy"],
+ ["Michael E", "Cheetham"],
+ ["Alison J", "Hardcastle"],
+ ["Petra", "Liskova"],
+ ["Stephen J", "Tuft"],
+ ["Alice E", "Davidson"]
],
- "publisher": "Oncology reports",
- "issn": "1791-2431",
- "date": "2010-05-01",
- "abstract": "Experimental evidence has revealed that several thymidylate synthase (TS) DNA polymorphisms modulate gene expression, which, in turn is known to be down-regulated by oestrogen receptor subtypes. Consequently, this process might be influenced by female hormones. Based on these data, we investigated whether patient's gender and TS polymorphism exert an interactive effect on the clinical evolution of patients with advanced colorectal cancer (CRC) subjected to 5 fluorouracil (5FU)-based adjuvant chemotherapy. A retrospective study was carried out on paraffin-embedded sections from 81 CRC patients. A variable tandem repeat (VNTR) of 28 bp, a G/C single nucleotide polymorphism (SNP), and a deletion of 6 bp (ins1494del 6 bp) were studied. Genotyping methods were polymerase chain reaction (PCR) for VNTR, and PCR followed by restriction length fragment polymorphism (PCR-RFLP) for SNP and ins1494del 6 bp. The effect of TS genotype and gender on overall and progression-free survival was assessed in univariate and multivariate (Cox regression model) tests. In male patients, the study of combined TS genotypes showed that G&6+/6+ was an adverse marker for overall (P=0.04; median: not reached) and progression-free survival (P=0.03; median: 12 months, 95% CI: 0-32.4). In the multivariate analysis, the concurrence of G&6+/6+ combination and male patients resulted in a 5.5-fold increased risk of relapse or disease progression (95% CI: 1-32.1; likelihood test P=0.004; interaction P=0.06). TS genotype did not affect survival among women. The present study supports that the effect of TS polymorphisms on the clinical evolution of advanced CRC patients is significantly influenced by gender.",
+ "publisher": "EBioMedicine",
+ "issn": "2352-3964",
+ "date": "2024-09-14",
+ "abstract": "Fuchs endothelial corneal dystrophy (FECD) is the most common repeat-mediated disease in humans. It exclusively affects corneal endothelial cells (CECs), with \u226481% of cases associated with an intronic TCF4 triplet repeat (CTG18.1). Here, we utilise optical genome mapping (OGM) to investigate CTG18.1 tissue-specific instability to gain mechanistic insights.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20372856"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:39278108"
},
{
- "id": "pmid:20005374",
+ "id": "pmid:30267097",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/20005374",
- "title": "A significant expansion of CD8+ CD28- T-suppressor cells in adult-to-adult living donor liver transplant recipients.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30267097",
+ "title": "CTG18.1 Expansion is the Best Classifier of Late-Onset Fuchs' Corneal Dystrophy Among 10 Biomarkers in a Cohort From the European Part of Russia.",
"type": "article-journal",
- "doi": "10.1016/j.transproceed.2009.09.072",
+ "doi": "10.1167/iovs.18-24590",
"authors": [
- ["Y-X", "Lin"],
- ["L-N", "Yan"],
- ["B", "Li"],
- ["L-L", "Wang"],
- ["T-F", "Wen"],
- ["Y", "Zeng"],
- ["W-T", "Wang"],
- ["J-C", "Zhao"],
- ["J-Y", "Yang"],
- ["M-Q", "Xu"],
- ["Y-K", "Ma"],
- ["Z-Y", "Chen"],
- ["Y-J", "Bai"]
+ ["Liubov O", "Skorodumova"],
+ ["Alexandra V", "Belodedova"],
+ ["Olga P", "Antonova"],
+ ["Elena I", "Sharova"],
+ ["Tatiana A", "Akopian"],
+ ["Oksana V", "Selezneva"],
+ ["Elena S", "Kostryukova"],
+ ["Boris E", "Malyugin"]
],
- "publisher": "Transplantation proceedings",
- "issn": "1873-2623",
- "date": "2009-12-01",
- "abstract": "The appearance of human regulatory CD8(+) CD28(-) T-suppressor (Ts) cells has been associated with a reduced need for maintenance immunosuppression in cadaveric heart- kidney transplant recipients and pediatric liver-intestine transplant recipients. However, few data are available in adult-to-adult living donor liver transplantation (A-A LDLT).",
+ "publisher": "Investigative ophthalmology & visual science",
+ "issn": "1552-5783",
+ "date": "2018-09-04",
+ "abstract": "To assess the occurrence and diagnostic performance of nine single-nucleotide variants (SNVs) in the TCF4, SLC4A11, LOXHD1, and AGBL1 genes and the CTG18.1 trinucleotide repeat expansion in a Russian cohort of Fuchs' endothelial corneal dystrophy (FECD) patients.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:20005374"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30267097"
},
{
- "id": "pmid:19306093",
+ "id": "pmid:40589716",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/19306093",
- "title": "Thymidylate synthetase allelic imbalance in clear cell renal carcinoma.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/40589716",
+ "title": "Intronic hexanucleotide repeat expansion in",
"type": "article-journal",
- "doi": "10.1007/s00280-009-0986-9",
+ "doi": "10.3892/br.2025.2016",
"authors": [
- ["Davide", "Colavito"],
- ["Giuseppe", "Cartei"],
- ["Massimo", "Dal Bianco"],
- ["Anna", "Stecca"],
- ["Fable", "Zustovich"],
- ["Maurizio", "Dalle Carbonare"],
- ["Eugenio", "Ragazzi"],
- ["Miriam", "Farina"],
- ["Eva", "Colombrino"],
- ["Alberta", "Leon"]
+ ["Sunisa", "Kanchanasutthiyakorn"],
+ ["Sakchai", "Chaiyamahapurk"],
+ ["Siraprapa", "Tongkobpetch"],
+ ["Kanokwan", "Santawong"],
+ ["Chalurmpon", "Srichomthong"],
+ ["Tippayakarn", "Klomchan"],
+ ["Chaiyaporn", "Virochsangaroon"],
+ ["Monnat", "Pongpanich"],
+ ["Prateep", "Warnnissorn"],
+ ["Sutatip", "Pongcharoen"],
+ ["Vorasuk", "Shotelersuk"]
],
- "publisher": "Cancer chemotherapy and pharmacology",
- "issn": "1432-0843",
- "date": "2009-03-22",
- "abstract": "To investigate the allelic status of the thymidylate synthetase (TYMS) gene, located at chromosome band 18p11.32, in renal cell carcinoma (RCC). TYMS is a key target of the 5-fluorouracil (5-FU)-based class of drugs, frequently considered in combination therapies in advanced RCC. TYMS variants, such as the TYMS polymorphic 5'-untranslated region variable number tandem repeat sequence (VNTR), are under investigation to guide 5-FU treatment. Yet, no information is available with regard to changes in TYMS allele frequencies in RCC malignances.",
+ "publisher": "Biomedical reports",
+ "issn": "2049-9442",
+ "date": "2025-06-12",
+ "abstract": "Hyperpigmentation presents a diverse clinical spectrum, largely influenced by genetic factors that remain incompletely understood. The present study describes a case of monozygotic twin girls aged 15 years with congenital progressive universal melanosis (CPUM) born to non-consanguineous unaffected parents. CPUM represents a novel clinical entity characterized by progressive widespread hyperpigmentation beginning at birth, without other accompanying symptoms. Skin biopsy and histopathological analysis were performed, followed by long-read whole-genome sequencing and short tandem repeat analysis. Gene expression was evaluated using reverse transcription-PCR, and protein levels were assessed by western blotting in cultured skin fibroblasts from the twins and unaffected controls. Long-read genome sequencing revealed a biallelic GATGGT repeat expansion of 210-259 repeat units within the third intron of the thymidylate synthase (",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19306093"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:40589716"
},
{
- "id": "pmid:19082493",
- "manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/19082493",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:19082493']' timed out after 3 seconds"
+ "id": "pmid:30533396",
+ "manubot_success": true,
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/30533396",
+ "title": "A Pharmacogenetic Study of VDR fok1 and TYMS Polymorphisms and Their Association With Glucocorticoid-Induced Osteonecrosis in Egyptian Children With Acute Lymphoblastic Leukemia.",
+ "type": "article-journal",
+ "doi": "10.3389/fonc.2018.00541",
+ "authors": [
+ ["Dina", "ElHarouni"],
+ ["Dina", "Yassin"],
+ ["Nesreen", "Ali"],
+ ["Seham", "Gohar"],
+ ["Iman", "Zaky"],
+ ["Hassan", "Adwan"],
+ ["Iman", "Sidhom"]
+ ],
+ "publisher": "Frontiers in oncology",
+ "issn": "2234-943X",
+ "date": "2018-11-23",
+ "abstract": "",
+ "language": "en",
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:30533396"
},
{
- "id": "pmid:18273818",
+ "id": "pmid:26745074",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/18273818",
- "title": "Size of the exon 1-CAG repeats of the androgen receptor gene employed as a molecular marker in the diagnosis of Turner syndrome in girls with short stature.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/26745074",
+ "title": "Thymidylate Synthase Polymorphisms and Risk of Lung Cancer among the Jordanian Population: a Case Control Study.",
"type": "article-journal",
- "doi": "10.4238/vol7-1gmr391",
+ "doi": "10.7314/apjcp.2015.16.18.8287",
"authors": [
- ["C C", "Figueiredo"],
- ["C", "Kochi"],
- ["C A", "Longui"],
- ["M N", "Rocha"],
- ["F", "Richeti"],
- ["N M A", "Evangelista"],
- ["L E P", "Calliari"],
- ["O", "Monte"]
+ ["Wiam Al", "Qasem"],
+ ["Al-Motassem", "Yousef"],
+ ["Mohammad", "Yousef"],
+ ["Ihab", "Manasreh"]
],
- "publisher": "Genetics and molecular research : GMR",
- "issn": "1676-5680",
- "date": "2008-01-22",
- "abstract": "Turner syndrome (TS) is one of the most common chromosomal abnormalities among girls. Complete monosomy of X chromosome is responsible for almost 50% of all cases of TS, and mosaicism and X anomaly are detected in the other half. It has already been demonstrated that early diagnosis of these children allows appropriate growth hormone treatment with better final height prognosis and introduction of estrogen at an ideal chronological age. Sixty-four short-stature girls were selected and the clinical data obtained were birth weight and height, weight and height at the first medical visit and target height. Other clinical data including cardiac and renal abnormalities, otitis, Hashimoto thyroiditis, cubitus valgus, short neck, widely separated nipples, and pigmented nevi were obtained from the patients' medical records. The aim of the present study was to evaluate the screening of a group of short-stature girls for TS based on the number of CAG repeats of the androgen receptor gene analyzed by GeneScan software. Patient samples with two alleles (heterozygous) were 49/64 (76.5%) and with one allele (homozygous) were 15/64 (23.5%). A karyotype was determined in 30 patients, 9 homozygous and 21 heterozygous. In the homozygous group, 6/9 were 45,X and 3/9 were 46,XX. In the heterozygous group, 17/21 were 46,XX, and 4/21 were TS patients with mosaicism (45,X/46,XX; 45,X/46XiXq; 46XdelXp). The pattern obtained by GeneScan in two patients with mosaicism in the karyotype was an imbalance between the peak heights of the two alleles, suggesting that this imbalance could be present when there is a mosaicism. The frequency of TS abnormalities (18.7%) did not differ between TS and 46,XX girls. Thus, it is important to accurately assess the incidence of TS in growth-retarded girls, even in the absence of other dysmorphisms. In this study, we diagnosed 6 cases of TS 45,X (9.4%) by molecular analysis, with a 100% sensitivity and 85% specificity. This molecular analysis was able to detect all cases of TS 45,X and the majority of mosaicisms, without the need for more X chromosome markers. In conclusion, determining the number of CAG repeats of the androgen receptor gene analyzed by GeneScan was a fast method with high sensitivity for the detection of TS 45,X, suggesting that it could be interesting as a method for screening a population of growth-retarded girls.",
+ "publisher": "Asian Pacific journal of cancer prevention : APJCP",
+ "issn": "2476-762X",
+ "date": "2015-01-01",
+ "abstract": "Thymidylate synthase (TS) catalyzes the methylation of deoxyuridylate to deoxythymidylate and is involved in DNA methylation, synthesis and repair. Two common polymorphisms have been reported, tandem repeats in the promoter-enhancer region (TSER), and 6bp ins/del in the 5'UTR, that are implicated in a number of human diseases, including cancer. The association between the two polymorphisms in risk for lung cancer (LC) was here investigated in the Jordanian population.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18273818"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:26745074"
},
{
- "id": "pmid:18267032",
+ "id": "pmid:24596472",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/18267032",
- "title": "ERCC2 2251A>C genetic polymorphism was highly correlated with early relapse in high-risk stage II and stage III colorectal cancer patients: a preliminary study.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/24596472",
+ "title": "Folate Levels and Polymorphisms in the Genes MTHFR, MTR, and TS in Colorectal Cancer.",
"type": "article-journal",
- "doi": "10.1186/1471-2407-8-50",
+ "doi": "10.4137/cmo.s12701",
"authors": [
- ["Ming-Yii", "Huang"],
- ["Wei-Yu", "Fang"],
- ["Su-Chen", "Lee"],
- ["Tian-Lu", "Cheng"],
- ["Jaw-Yuan", "Wang"],
- ["Shiu-Ru", "Lin"]
+ ["Helena", "Taflin"],
+ ["Yvonne", "Wettergren"],
+ ["Elisabeth", "Odin"],
+ ["G\u00f6ran", "Carlsson"],
+ ["Kristoffer", "Derwinger"]
],
- "publisher": "BMC cancer",
- "issn": "1471-2407",
- "date": "2008-02-12",
- "abstract": "Early relapse in colorectal cancer (CRC) patients is attributed mainly to the higher malignant entity (such as an unfavorable genotype, deeper tumor invasion, lymph node metastasis and advance cancer stage) and poor response to chemotherapy. Several investigations have demonstrated that genetic polymorphisms in drug-targeted genes, metabolizing enzymes, and DNA-repairing enzymes are all strongly correlated with inter-individual differences in the efficacy and toxicity of many treatment regimens. This preliminary study attempts to identify the correlation between genetic polymorphisms and clinicopathological features of CRC, and evaluates the relationship between genetic polymorphisms and chemotherapeutic susceptibility of Taiwanese CRC patients. To our knowledge, this study discusses, for the first time, early cancer relapse and its indication by multiple genes.",
+ "publisher": "Clinical Medicine Insights. Oncology",
+ "issn": "1179-5549",
+ "date": "2014-02-17",
+ "abstract": "The aim of the study was to explore and describe the effect of polymorphisms in folate-associated genes regarding the levels of different folate forms and their distribution in tumors and mucosa in patients with colorectal cancer.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:18267032"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:24596472"
},
{
- "id": "pmid:17278107",
+ "id": "pmid:21449681",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/17278107",
- "title": "Identification of a novel single nucleotide polymorphism in the first tandem repeat sequence of the thymidylate synthase 2R allele.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/21449681",
+ "title": "Use of a comprehensive panel of biomarkers to predict response to a fluorouracil-oxaliplatin regimen in patients with metastatic colorectal cancer.",
"type": "article-journal",
- "doi": "10.1002/ijc.22568",
+ "doi": "10.2217/pgs.10.196",
"authors": [
- ["Lisa F", "Lincz"],
- ["Fiona E", "Scorgie"],
- ["Madhu B", "Garg"],
- ["Stephen P", "Ackland"]
+ ["Maria J", "Lamas"],
+ ["Goretti", "Duran"],
+ ["Emilia", "Balboa"],
+ ["Beatriz", "Bernardez"],
+ ["Manuel", "Touris"],
+ ["Yolanda", "Vidal"],
+ ["Elena", "Gallardo"],
+ ["Rafael", "Lopez"],
+ ["Angel", "Carracedo"],
+ ["Francisco", "Barros"]
],
- "publisher": "International journal of cancer",
- "issn": "0020-7136",
- "date": "2007-05-01",
- "abstract": "Thymidylate synthase (TS) activity is an important determinant of response to chemotherapy with fluoropyrimidine prodrugs and its expression is largely determined by the number of functional upstream stimulatory factor (USF) E-box consensus elements present in the 5'regulatory region of the TYMS gene. Two known polymorphisms in this area, a variable number of tandem repeat (VNTR) consisting of 2 or 3 repeats (2R/3R) of a 28-bp sequence and a further G > C single nucleotide substitution within the second repeat of the 3R, result in genotypes with between 2 and 4 functional repeats in most humans. Here, we identify a further G > C SNP in the first repeat of the TYMS 2R allele, which effectively abolishes the only functional USF protein binding site in this promoter. The frequency of the new allele was found to be 4.2% (95% CI = 1.4-9.6%), accounting for 8.8% (95% CI = 2.9-19.3%) of all 2R alleles in our patient cohort. Thus, we observed that the lowest number of inherited functional binding sites is 1 instead of 2 as previously thought, and could potentially be 0 in a homozygous individual. This would severely decrease TS expression and may have implications for predicting efficacy and toxicity of therapy with commonly used fluorouracil-based therapy regimes.",
+ "publisher": "Pharmacogenomics",
+ "issn": "1744-8042",
+ "date": "2011-03-01",
+ "abstract": "Polymorphisms in the metabolism, detoxification or DNA repair pathways have been proposed as potential predictors of response to 5-fluorouracil and oxaliplatin. We have studied the predictive value of a set of germline genetic polymorphisms in metastatic colorectal cancer patients treated with mFolfox-6.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17278107"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:21449681"
},
{
- "id": "pmid:17273745",
+ "id": "pmid:19082493",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/17273745",
- "title": "Combined analysis of genetic polymorphisms in thymidylate synthase, uridine diphosphate glucoronosyltransferase and X-ray cross complementing factor 1 genes as a prognostic factor in advanced colorectal cancer patients treated with 5-fluorouracil plus oxaliplatin or irinotecan.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/19082493",
+ "title": "Combination of polymorphisms within 5' and 3' untranslated regions of thymidylate synthase gene modulates survival in 5 fluorouracil-treated colorectal cancer patients.",
"type": "article-journal",
"doi": "",
"authors": [
- ["Eva", "Martinez-Balibrea"],
- ["Jose Luis", "Manzano"],
- ["Anna", "Martinez-Cardus"],
- ["Teresa", "Moran"],
- ["Beatriz", "Cirauqui"],
- ["Silvia", "Catot"],
- ["Miguel", "Taron"],
- ["Albert", "Abad"]
+ ["Mar\u00eda-Encarnaci\u00f3n", "Fern\u00e1ndez-Contreras"],
+ ["Jos\u00e9 Javier", "S\u00e1nchez-Hern\u00e1ndez"],
+ ["Enrique", "Gonz\u00e1lez"],
+ ["Bel\u00e9n", "Herr\u00e1ez"],
+ ["Irene", "Dom\u00ednguez"],
+ ["Mar\u00eda", "Lozano"],
+ ["Mar\u00eda-Luisa", "Garc\u00eda De Paredes"],
+ ["Alberto", "Mu\u00f1oz"],
+ ["Carlos", "Gamallo"]
],
- "publisher": "Oncology reports",
- "issn": "1021-335X",
- "date": "2007-03-01",
- "abstract": "The aim of this study was to investigate the influence of combining thymidylate synthase (TS), X-ray cross complementing factor 1 (XRCC1) and uridine diphosphate glucoronosyltransferase (UGT1A1 *28) polymorphism genotypes in response rate and time to progression (TTP) in metastatic colorectal cancer patients treated with 5-fluorouracil (5-FU) plus irinotecan or oxaliplatin (OXA). PCR, RFLP, allelic discrimination and direct sequencing were performed to elucidate TS, XRCC1 and UGT1A1 *28 genotypes in blood from 71 patients. Patients with a number of favourable genotypes (NFG) > or =1 had a lower progression rate and a better TTP than patients with NFG=0 (log-rank p<0.03). In the OXA + 5-FU group, patients with the TS 5' single nucleotide polymorphism and/or XRCC1 genotypes favourable to treatment had a better TTP (log-rank p=0.02). The TS 5' tandem repeat polymorphism and the NFG were independent prognostic factors in the Cox-based multivariate analysis (p<0.03). These results confirm the influence on patient out-come of these genetic polymorphisms and the possibility of studying them together to predict the outcome in first-line treated colorectal cancer patients.",
+ "publisher": "International journal of oncology",
+ "issn": "1019-6439",
+ "date": "2009-01-01",
+ "abstract": "In the present study we explored the effect of three polymorphisms of the TS gene on overall and progression- free survival of colorectal cancer (CRC) patients subjected to 5FU chemotherapy. A 28 bp variable number of tandem repeats (VNTR), a G/C single nucleotide polymorphism (SNP), and a deletion of 6 bp at position 1494 were studied. The possible combined effect of these DNA polymorphisms on the clinical outcome of patients was also evaluated. A retrospective study was carried out on paraffin-embedded sections from 113 patients diagnosed of advanced CRC. TS genotyping methods were polymerase chain reaction (PCR) for VNTR and PCR, followed by restriction length fragment polymorphism (PCR-RFLP) for SNP and ins/del 6 bp. To study the combined effect of TS polymorphisms, four categories were defined accordingly to the level of expression attributed to SNP and ins/del 6 bp genotypes: C&allele 6-, C&6+/6+, G&allele6- and G&6+/6+. VNTR and ins/del 6 bp genotypes varied with tumour anatomical site: 2R/2R genotype was rare in left-sided tumours (7.0% vs. 26.3% of right-sided and 24.1% of rectal cancers; P<0.01), where the variant allele 6- was very frequent (69.0%). Instead, most patients with right-sided tumours were wild-type homozygous 6+/6+ (63.9%) (P<0.01). Heterozygous 6+/6- genotype was more frequent among tumours classified as C (50.0%) and D (76.5%) Dukes stages (P=0.05). None of the studied polymorphisms alone affected overall or progression-free survival (PFS). C&6+/6+ and G&6+/6+ combined genotypes were respectively associated to the best and worst PFS (P=0.03 when compared with each other), while combinations carrying the allele 6- determined an intermediate evolution that might be indicative of a variable response to chemotherapy. The rate of Dukes B stage tumours was unexpectedly high (59.1%) among patients with the unfavourable G&6+/6+ combination. In our study the combination of high TS expression genotypes G&6+/6+ identifies a group of high risk within CRC patients treated with 5FU.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:17273745"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:19082493"
},
{
- "id": "pmid:16929515",
+ "id": "pmid:15749593",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/16929515",
- "title": "The thymidylate synthase tandem repeat promoter polymorphism: A predictor for tumor-related survival in neoadjuvant treated locally advanced gastric cancer.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/15749593",
+ "title": "Thymidylate synthase gene polymorphism as a prognostic factor for colon cancer.",
"type": "article-journal",
- "doi": "10.1002/ijc.22235",
+ "doi": "10.1016/j.gassur.2004.09.030",
"authors": [
- ["Katja", "Ott"],
- ["Holger", "Vogelsang"],
- ["Noemi", "Marton"],
- ["Karen", "Becker"],
- ["Florian", "Lordick"],
- ["Michael", "Kobl"],
- ["Christoph", "Schuhmacher"],
- ["Alexander", "Novotny"],
- ["James", "Mueller"],
- ["Ulrich", "Fink"],
- ["Kurt", "Ulm"],
- ["J\u00f6rg R\u00fcdiger", "Siewert"],
- ["Heinz", "H\u00f6fler"],
- ["Gisela", "Keller"]
+ ["Kwang Wook", "Suh"],
+ ["Joo Hyung", "Kim"],
+ ["Young Bae", "Kim"],
+ ["Jeongmi", "Kim"],
+ ["Soohyun", "Jeong"]
],
- "publisher": "International journal of cancer",
- "issn": "0020-7136",
- "date": "2006-12-15",
- "abstract": "We evaluated DNA polymorphisms in the thymidylate synthase (TS) and 5,10-methylene-tetrahydrofolate reductase (MTHFR) genes for an association with response and survival in locally advanced gastric cancer treated with 5-FU based preoperative chemotherapy (CTx). DNA of 238 patients (CTx-group: total n = 135, completely resected (R0) n = 102; without CTx: R0 n = 103) was isolated from blood or from nontumorous tissues. In the CTx-group, genotyping of the tandem repeat and the G/C polymorphism in the triple repeat in the promoter region of the TS gene and of the C677T polymorphism of the MTHFR gene was performed. None of the TS or MTHFR genotypes were associated with histopathological response and only the TS tandem repeat polymorphism was significantly related to survival (all patients n = 135, p = 0.002; R0 resected patients n = 102, p = 0.007; log-rank test). Multivariate analysis revealed ypN (p < 0.001) and the TS tandem repeat polymorphism as independent prognostic factors in the CTx-R0-group (p = 0.003). Analyzing the prognostic significance of the TS polymorphisms in the R0-group without CTx, TS genotypes were not significantly associated with survival. Comparing survival between R0 patients with and without CTx in the respective TS genotype groups of the tandem repeat polymorphism, a significant survival benefit for the patients with CTx was found for the 2rpt/2rpt (n = 49; p = 0.002) and 2rpt/3rpt genotypes (n = 99; p = 0.004), but not for the 3rpt/3rpt genotype (n = 57; p = 0.93). Patients' survival after CTx was associated with the TS tandem repeat polymorphism. CTx did not improve survival of patients with the 3rpt/3rpt genotype. Thus, a different therapy might be more appropriate for these patients.",
+ "publisher": "Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract",
+ "issn": "1091-255X",
+ "date": "2005-03-01",
+ "abstract": "The human thymidylate synthase (TS) gene promoter is polymorphic, having either double or triple tandem repeats of a 28-base-pair (bp) sequence. Here, we determined the significance of this polymorphism in predicting the clinical outcomes for patients with colon cancer. We reviewed 121 consecutive patients with stage II or III colon cancer who underwent a curative resection. After DNA extraction from paraffin-embedded tissues, the promoter region of the TS gene was amplified by polymerase chain reaction. In addition to the conventional prognostic factors, patient survivals were compared with regard to the pattern of TS polymorphism. Sixty-eight subjects were homozygotes for the triple-repeat variant (250 bp, group A), and 53 subjects (group B) were either homozygotes for the double-repeat variant (220 bp) or heterozygotes (220 and 250 bp). We found a significant difference between groups A and B in survival (53% versus 80%, P=0.0481). The difference was particularly significant in the patients with stage III disease (41% versus 77%, P=0.0414). Tumor stage and the TS polymorphism were identified as significant prognostic factors by multivariate analysis. We found the TS polymorphism to be a significant and independent prognostic factor for colon cancer.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16929515"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15749593"
},
{
- "id": "pmid:16818689",
+ "id": "pmid:3002689",
"manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/16818689",
- "title": "Orotate phosphoribosyltransferase gene polymorphism predicts toxicity in patients treated with bolus 5-fluorouracil regimen.",
+ "link": "https://www.ncbi.nlm.nih.gov/pubmed/3002689",
+ "title": "Cytomegalovirus infection in cardiac transplant recipients associated with chronic T cell subset ratio inversion with expansion of a Leu-7+ TS-C+ subset.",
"type": "article-journal",
- "doi": "10.1158/1078-0432.ccr-05-2665",
+ "doi": "",
"authors": [
- ["Wataru", "Ichikawa"],
- ["Takehiro", "Takahashi"],
- ["Kenichi", "Suto"],
- ["Yasutsuna", "Sasaki"],
- ["Renzo", "Hirayama"]
+ ["P", "Maher"],
+ ["C M", "O'Toole"],
+ ["T G", "Wreghitt"],
+ ["D J", "Spiegelhalter"],
+ ["T A", "English"]
],
- "publisher": "Clinical cancer research : an official journal of the American Association for Cancer Research",
- "issn": "1078-0432",
- "date": "2006-07-01",
- "abstract": "We investigated whether the determination of orotate phosphoribosyltransferase (OPRT) and thymidylate synthase (TYMS) polymorphisms could predict the toxicity of 5-fluorouracil (5-FU) in colorectal cancer patients.",
+ "publisher": "Clinical and experimental immunology",
+ "issn": "0009-9104",
+ "date": "1985-12-01",
+ "abstract": "Lymphocyte subsets were analysed in 18 patients during the first 3 years after cardiac transplantation. The patients received Cyclosporin A and prednisolone for maintenance immunosuppression. Serological evidence of active cytomegalovirus (CMV) infection was found in 13 cases (72%), and in 12 of these an inversion usually of the T helper/T suppressor-cytotoxic ratio (TH/TS-C) was detected. T subset inversion usually preceded the diagnostic rise in CMV antibody titre. In 69% of patients with CMV the TH/TS-C ratio remained inverted throughout follow-up (245-951 days). Persistent T subset inversion was not found in all five patients who lacked serological evidence of active CMV. Chronic inversion consisted of an average increase in TS-C of 152% and an average decline in TH cells of 31% as compared to CMV negative patients. The proportion of lymphoid cells reacting with a phenotypic marker for natural killer (NK) cells (Leu-7) was increased by 83%. These alterations were also reflected in the absolute numbers of cells with these markers. Two-colour immunofluorescence analysis revealed that the expanded TS-C population present during chronic inversion was predominantly Leu-7+. As TS-C+ Leu-7+ cells in healthy persons may be hyporesponsive NK cells, a sustained increase in this cell type in allograft recipients could further reduce immunocompetence, thereby predisposing to superinfection or malignancy.",
"language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16818689"
+ "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:3002689"
+},
+{
+ "id": "omim:309548",
+ "manubot_success": false,
+ "link": "https://omim.org/entry/309548",
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+},
+{
+ "id": "omim:309510",
+ "manubot_success": false,
+ "link": "https://omim.org/entry/309510",
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+},
+{
+ "id": "omim:308350",
+ "manubot_success": false,
+ "link": "https://omim.org/entry/308350",
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+},
+{
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+ "manubot_success": false,
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+{
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+{
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+{
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+ "manubot_success": false,
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+ "manubot_success": false,
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+},
+{
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+ "manubot_success": false,
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+{
+ "id": "omim:615945",
+ "manubot_success": false,
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+{
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+ "manubot_success": false,
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+ "manubot_success": false,
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+},
+{
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+ "manubot_success": false,
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+{
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+},
+{
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+ "manubot_success": false,
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+{
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+ "manubot_success": false,
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+{
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+ "manubot_success": false,
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+{
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+ "manubot_success": false,
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+{
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+ "manubot_success": false,
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+{
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+ "manubot_success": false,
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+{
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+ "manubot_success": false,
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+{
+ "id": "omim:601846",
+ "manubot_success": false,
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+{
+ "id": "omim:258450",
+ "manubot_success": false,
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+},
+{
+ "id": "omim:157640",
+ "manubot_success": false,
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+},
+{
+ "id": "omim:604326",
+ "manubot_success": false,
+ "link": "https://omim.org/entry/604326",
+ "note": "WARNING: Manubot does not support url:https://omim.org/entry/604326. Skipping"
+},
+{
+ "id": "omim:616488",
+ "manubot_success": false,
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},
{
- "id": "pmid:16182121",
- "manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/16182121",
- "title": "Relationships between promoter polymorphisms in the thymidylate synthase gene and mRNA levels in colorectal cancers.",
- "type": "article-journal",
- "doi": "10.1016/j.ejca.2005.06.016",
- "authors": [
- ["Maria", "Morganti"],
- ["Monica", "Ciantelli"],
- ["Beatrice", "Giglioni"],
- ["Anna L", "Putignano"],
- ["Stefania", "Nobili"],
- ["Laura", "Papi"],
- ["Ida", "Landini"],
- ["Cristina", "Napoli"],
- ["Rosa", "Valanzano"],
- ["Fabio", "Cianchi"],
- ["Vieri", "Boddi"],
- ["Francesco", "Tonelli"],
- ["Camillo", "Cortesini"],
- ["Teresita", "Mazzei"],
- ["Maurizio", "Genuardi"],
- ["Enrico", "Mini"]
- ],
- "publisher": "European journal of cancer (Oxford, England : 1990)",
- "issn": "0959-8049",
- "date": "2005-09-01",
- "abstract": "Thymidylate synthase (TS) intratumoural expression may be a prognostic marker and predict outcome of 5-fluorouracil (5-FU)-based chemotherapy in colorectal cancer patients. The TS gene promoter enhancer region contains two different polymorphisms which can influence TS mRNA transcriptional and translational efficiency: a polymorphic tandem repeat sequence (2 or 3 repeats; 2R and 3R) and a single nucleotide polymorphism (SNP), G > C, within the second repeat of the 3R alleles. We studied the relationship between tumoural TS mRNA expression levels and TS gene polymorphisms in the colonic mucosa of 48 colorectal cancer patients. The 3R/3R genotype was characterised by higher TS mRNA levels in the tumour than the 2R/2R-2R/3R genotypes (P = 0.071). Regarding the relationship with the SNP polymorphism, a statistically significant difference in TS gene expression between the 3RG/3RG genotype and 2R/2R-2R/3RC-2R/3RG genotype subset was observed (P = 0.017). No statistically significant correlation was observed between experimental data and baseline clinical-pathological characteristics as well as clinical outcome in the relatively small patient series investigated. This is the first study reporting an association between the TS intra-repeat SNP and gene expression levels in colorectal cancer patients. These results suggest that in 3R/3R patients, the G > C polymorphism may be an important factor in determining TS mRNA expression levels, and warrant further investigation of the role of TS promoter polymorphisms as predictors of sensitivity to 5-FU-based chemotherapy in larger case series.",
- "language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:16182121"
+ "id": "omim:601068",
+ "manubot_success": false,
+ "link": "https://omim.org/entry/601068",
+ "note": "WARNING: Manubot does not support url:https://omim.org/entry/601068. Skipping"
},
{
- "id": "pmid:15749593",
+ "id": "omim:300123",
"manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/15749593",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:15749593']' timed out after 3 seconds"
+ "link": "https://omim.org/entry/300123",
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},
{
- "id": "pmid:15510613",
- "manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/15510613",
- "title": "Methylenetetrahydrofolate reductase and thymidylate synthase polymorphisms are not associated with breast cancer risk or phenotype.",
- "type": "article-journal",
- "doi": "",
- "authors": [
- ["Fabienne", "Grieu"],
- ["Brenda", "Powell"],
- ["John", "Beilby"],
- ["Barry", "Iacopetta"]
- ],
- "publisher": "Anticancer research",
- "issn": "0250-7005",
- "date": "2004-01-01",
- "abstract": "Aberrations in folate metabolism contribute to the risk of cancer via effects on the synthesis, methylation and repair of DNA. Functional genetic variants in the methylene tetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) genes may be risk factors for breast cancer because of their central roles in cellular folate metabolism.",
- "language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15510613"
+ "id": "omim:607136",
+ "manubot_success": false,
+ "link": "https://omim.org/entry/607136",
+ "note": "WARNING: Manubot does not support url:https://omim.org/entry/607136. Skipping"
},
{
- "id": "pmid:15115918",
- "manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/15115918",
- "title": "A 6 bp polymorphism in the thymidylate synthase gene causes message instability and is associated with decreased intratumoral TS mRNA levels.",
- "type": "article-journal",
- "doi": "10.1097/00008571-200405000-00007",
- "authors": [
- ["Michael V", "Mandola"],
- ["Jan", "Stoehlmacher"],
- ["Wu", "Zhang"],
- ["Susan", "Groshen"],
- ["Mimi C", "Yu"],
- ["Syma", "Iqbal"],
- ["Heinz-Josef", "Lenz"],
- ["Robert D", "Ladner"]
- ],
- "publisher": "Pharmacogenetics",
- "issn": "0960-314X",
- "date": "2004-05-01",
- "abstract": "A 6 bp deletion polymorphism in the thymidylate synthase (TS) gene was investigated in order to determine its function.",
- "language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:15115918"
+ "id": "omim:187500",
+ "manubot_success": false,
+ "link": "https://omim.org/entry/187500",
+ "note": "WARNING: Manubot does not support url:https://omim.org/entry/187500. Skipping"
},
{
- "id": "pmid:12460463",
- "manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/12460463",
- "title": "Functional polymorphism of the thymidylate synthase gene in colorectal cancer accompanied by frequent loss of heterozygosity.",
- "type": "article-journal",
- "doi": "10.1111/j.1349-7006.2002.tb01227.x",
- "authors": [
- ["Kazuyuki", "Kawakami"],
- ["Yoshinori", "Ishida"],
- ["Kathleen D", "Danenberg"],
- ["Kenji", "Omura"],
- ["Go", "Watanabe"],
- ["Peter V", "Danenberg"]
- ],
- "publisher": "Japanese journal of cancer research : Gann",
- "issn": "0910-5050",
- "date": "2002-11-01",
- "abstract": "The thymidylate synthase (TS) gene has a polymorphic repeated sequence in its 5'-untranslated region. The repeat length is associated with TS protein expression, which suggests that we may be able to predict the efficacy of 5-fluorouracil (5-FU)-based chemotherapy from a patient's TS genotype determined through analysis of normal tissue obtained non-invasively. However, it is not yet elucidated whether the TS genotype is identical in tumor and normal tissue. In this study, we investigated the TS genotype in 151 matched tumor and normal DNA samples isolated from colorectal cancer and adjacent normal tissues by PCR analysis. The results showed that TS genotypes are identical in normal and tumor tissues of homozygous individuals, suggesting that the repeat sequence is stable through carcinogenesis. However, in heterozygous samples, an imbalance between the 2R and 3R alleles in the tumor DNA was frequently observed, suggesting loss of heterozygosity (LOH) at the TS locus. Detailed LOH analysis revealed that 62% (31 of 50) of 2R/3R-heterozygous samples had LOH. Frequent LOH at the TS locus was confirmed by RT-PCR of TS mRNA and microsatellite analysis using the marker D18S59, located on 18p11.3. There was no difference in the expressions of TS mRNA and TS protein between LOH and non-LOH samples. However, when the heterozygous genotype bearing LOH was subdivided according to the number of repeats, the cancer tissue with 2R/loss genotype expressed a significantly lower level of TS protein than did that with 3R/loss genotype. The results suggest that the difference in TS genotype between tumor and normal tissue due to LOH should be considered when the genotype is analyzed with normal tissue, such as peripheral blood cells, because it is important for TS protein expression.",
- "language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:12460463"
+ "id": "omim:613267",
+ "manubot_success": false,
+ "link": "https://omim.org/entry/613267",
+ "note": "WARNING: Manubot does not support url:https://omim.org/entry/613267. Skipping"
},
{
- "id": "pmid:11913730",
- "manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/11913730",
- "title": "Thymidylate synthase gene polymorphism determines response and toxicity of 5-FU chemotherapy.",
- "type": "article-journal",
- "doi": "10.1038/sj.tpj.6500012",
- "authors": [
- ["S T", "Pullarkat"],
- ["J", "Stoehlmacher"],
- ["V", "Ghaderi"],
- ["Y P", "Xiong"],
- ["S A", "Ingles"],
- ["A", "Sherrod"],
- ["R", "Warren"],
- ["D", "Tsao-Wei"],
- ["S", "Groshen"],
- ["H J", "Lenz"]
- ],
- "publisher": "The pharmacogenomics journal",
- "issn": "1470-269X",
- "date": "2001-01-01",
- "abstract": "Thymidylate synthase (TS) catalyses the conversion of deoxy-uridylate to deoxy-thymidylate and is essential for DNA synthesis. The human TS gene promoter is polymorphic, having either double or triple tandem repeats of a 28-bp sequence. Here we determined the significance of this polymorphism in humans and its prediction for clinical outcome of patients with metastatic colorectal cancer treated with 5-fluorouracil. The TS mRNA level was analyzed using RT-PCR. Individuals homozygous for the triple repeat variant (L/L) had 3.6 times higher TS mRNA levels compared to those homozygous for the double repeat variant (S/S) in tumor tissue (P = 0.004). We tested 50 patients with disseminated colorectal cancer who received 5-FU treatment to determine whether this TS polymorphism will predict clinical outcome. We found individuals with S/S genotype had a response rate of 50% (4/8) when compared to 9% (2/22) in those with L/L and 15% (3/20) in those with S/L genotype (P = 0.041). Patients with L/L had less severe side effects to 5-FU (P = 0.008). The data suggest that genotyping for the TS polymorphism may have the potential to identify patients more likely to respond to 5-FU based chemotherapy.",
- "language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:11913730"
+ "id": "omim:619216",
+ "manubot_success": false,
+ "link": "https://omim.org/entry/619216",
+ "note": "WARNING: Manubot does not support url:https://omim.org/entry/619216. Skipping"
},
{
- "id": "pmid:10652619",
- "manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/10652619",
- "title": "Polymorphic tandem repeats in the thymidylate synthase gene is associated with its protein expression in human gastrointestinal cancers.",
- "type": "article-journal",
- "doi": "",
- "authors": [
- ["K", "Kawakami"],
- ["K", "Omura"],
- ["E", "Kanehira"],
- ["Y", "Watanabe"]
- ],
- "publisher": "Anticancer research",
- "issn": "0250-7005",
- "date": "1999-01-01",
- "abstract": "Thymidylate synthase (TS) is a target enzyme of 5-fluorouracil (5-FU), and the TS gene has a polymorphic tandem repeated sequence in the 5'-untranslated region. We investigated the polymorphism on the repeat length of the TS gene and its relation to the number of 5-fluoro-dUMP (FdUMP) binding sites in human gastrointestinal cancers.",
- "language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:10652619"
+ "id": "omim:600223",
+ "manubot_success": false,
+ "link": "https://omim.org/entry/600223",
+ "note": "WARNING: Manubot does not support url:https://omim.org/entry/600223. Skipping"
},
{
- "id": "pmid:3002689",
+ "id": "omim:314390",
"manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/3002689",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:3002689']' timed out after 3 seconds"
+ "link": "https://omim.org/entry/314390",
+ "note": "WARNING: Manubot does not support url:https://omim.org/entry/314390. Skipping"
},
{
- "id": "pmid:39666847",
+ "id": "omim:616181",
"manubot_success": false,
- "link": "https://pubmed.ncbi.nlm.nih.gov/39666847",
- "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'pmid:39666847']' timed out after 3 seconds"
+ "link": "https://omim.org/entry/616181",
+ "note": "WARNING: Manubot does not support url:https://omim.org/entry/616181. Skipping"
},
{
- "id": "pmid:38684900",
- "manubot_success": true,
- "link": "https://www.ncbi.nlm.nih.gov/pubmed/38684900",
- "title": "A GGC-repeat expansion in ZFHX3 encoding polyglycine causes spinocerebellar ataxia type 4 and impairs autophagy.",
- "type": "article-journal",
- "doi": "10.1038/s41588-024-01719-5",
- "authors": [
- ["Karla P", "Figueroa"],
- ["Caspar", "Gross"],
- ["Elena", "Buena-Atienza"],
- ["Sharan", "Paul"],
- ["Mandi", "Gandelman"],
- ["Naseebullah", "Kakar"],
- ["Marc", "Sturm"],
- ["Nicolas", "Casadei"],
- ["Jakob", "Admard"],
- ["Joohyun", "Park"],
- ["Christine", "Z\u00fchlke"],
- ["Yorck", "Hellenbroich"],
- ["Jelena", "Pozojevic"],
- ["Saranya", "Balachandran"],
- ["Kristian", "H\u00e4ndler"],
- ["Simone", "Zittel"],
- ["Dagmar", "Timmann"],
- ["Friedrich", "Erdlenbruch"],
- ["Laura", "Herrmann"],
- ["Thomas", "Feindt"],
- ["Martin", "Zenker"],
- ["Thomas", "Klopstock"],
- ["Claudia", "Dufke"],
- ["Daniel R", "Scoles"],
- ["Arnulf", "Koeppen"],
- ["Malte", "Spielmann"],
- ["Olaf", "Riess"],
- ["Stephan", "Ossowski"],
- ["Tobias B", "Haack"],
- ["Stefan M", "Pulst"]
- ],
- "publisher": "Nature genetics",
- "issn": "1546-1718",
- "date": "2024-04-29",
- "abstract": "Despite linkage to chromosome 16q in 1996, the mutation causing spinocerebellar ataxia type 4 (SCA4), a late-onset sensory and cerebellar ataxia, remained unknown. Here, using long-read single-strand whole-genome sequencing (LR-GS), we identified a heterozygous GGC-repeat expansion in a large Utah pedigree encoding polyglycine (polyG) in zinc finger homeobox protein 3 (ZFHX3), also known as AT-binding transcription factor 1 (ATBF1). We queried 6,495 genome sequencing datasets and identified the repeat expansion in seven additional pedigrees. Ultrarare DNA variants near the repeat expansion indicate a common distant founder event in Sweden. Intranuclear ZFHX3-p62-ubiquitin aggregates were abundant in SCA4 basis pontis neurons. In fibroblasts and induced pluripotent stem cells, the GGC expansion led to increased ZFHX3 protein levels and abnormal autophagy, which were normalized with small interfering RNA-mediated ZFHX3 knockdown in both cell types. Improving autophagy points to a therapeutic avenue for this novel polyG disease. The coding GGC-repeat expansion in an extremely G+C-rich region was not detectable by short-read whole-exome sequencing, which demonstrates the power of LR-GS for variant discovery.",
- "language": "en",
- "note": "This CSL Item was generated by Manubot v0.6.1 from its persistent identifier (standard_id).\nstandard_id: pubmed:38684900"
+ "id": "malacard:KNS007",
+ "manubot_success": false,
+ "link": "https://www.malacards.org/card/KNS007",
+ "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'url:https://www.malacards.org/card/KNS007']' timed out after 3 seconds"
+},
+{
+ "id": "genereviews:NBK1384",
+ "manubot_success": false,
+ "link": "https://www.ncbi.nlm.nih.gov/books/NBK1384",
+ "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'url:https://www.ncbi.nlm.nih.gov/books/NBK1384']' timed out after 3 seconds"
+},
+{
+ "id": "genereviews:NBK1281",
+ "manubot_success": false,
+ "link": "https://www.ncbi.nlm.nih.gov/books/NBK1281",
+ "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'url:https://www.ncbi.nlm.nih.gov/books/NBK1281']' timed out after 3 seconds"
+},
+{
+ "id": "genereviews:NBK1305",
+ "manubot_success": false,
+ "link": "https://www.ncbi.nlm.nih.gov/books/NBK1305",
+ "note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'url:https://www.ncbi.nlm.nih.gov/books/NBK1305']' timed out after 3 seconds"
},
{
"id": "isbn:978-3-031-66932-3",
"manubot_success": false,
"note": "WARNING: Manubot could not generate citation: Command '['manubot', 'cite', 'isbn:978-3-031-66932-3']' timed out after 3 seconds"
+},
+{
+ "id": "pmid:25101480",
+ "manubot_success": false,
+ "link": "https://pubmed.ncbi.nlm.nih.gov/25101480",
+ "note": "WARNING: Couldn't parse Manubot response: list index out of range"
+},
+{
+ "id": "pmid:29939637",
+ "manubot_success": false,
+ "link": "https://pubmed.ncbi.nlm.nih.gov/29939637",
+ "note": "WARNING: Couldn't parse Manubot response: list index out of range"
+},
+{
+ "id": "pmid:39666847",
+ "manubot_success": false,
+ "link": "https://pubmed.ncbi.nlm.nih.gov/39666847",
+ "note": "WARNING: Couldn't parse Manubot response: list index out of range"
}]
\ No newline at end of file
diff --git a/data/STRchive-disease-loci.T2T-chm13.bed b/data/STRchive-disease-loci.T2T-chm13.bed
index 9c2bec24..f47698eb 100644
--- a/data/STRchive-disease-loci.T2T-chm13.bed
+++ b/data/STRchive-disease-loci.T2T-chm13.bed
@@ -55,7 +55,7 @@ chr17 17754961 17755053 FAME8_RAI1 RAI1 TTTTA TTTCA 9 AD Familial adult myocloni
chr17 81047404 81047534 RCPS_EIF4A3 EIF4A3 CCTCGCTGTGCCGCTGCCGA CCTCGCTGTGCCGCTGCCGA 14 AR Richieri-Costa-Pereira syndrome
chr18 821235 821905 CPUM_TYMS TYMS GATGGT GATGGT 210 AR Congenital Progressive Universal Melanosis
chr18 55789233 55789288 FECD3_TCF4 TCF4 CAG CAG 51 AD Fuchs endothelial corneal dystrophy 3
-chr19 4494212 4497342 MRUPAV_PLIN4 PLIN4 TGGTGTCCACGCCGGTCTGGATGGTTCCTTTGGCCACATTCATGGCACCAGTCACCCCACTACAGACGGTGTCCTTGGTACCTGTTAGGACAGTCTTAC TGGTGTCCACGCCGGTCTGGATGGTTCCTTTGGCCACATTCATGGCACCAGTCACCCCACTACAGACGGTGTCCTTGGTACCTGTTAGGACAGTCTTAC 39 AD Myopathy with Rimmed Ubiquitin-Positive Autophagic Vacuolation, PLIN4-Related Myopathy
+chr19 4494212 4497342 MRUPAV_PLIN4 PLIN4 TGGTGTCCACGCCGGTCTGGATGGTTCCTTTGGCCACATTCATGGCACCAGTCACCCCACTACAGACGGTGTCCTTGGTACCTGTTAGGACAGTCTTAC TGGTGTCCACGCCGGTCTGGATGGTTCCTTTGGCCACATTCATGGCACCAGTCACCCCACTACAGACGGTGTCCTTGGTACCTGTTAGGACAGTCTTAC 37 AD Myopathy with Rimmed Ubiquitin-Positive Autophagic Vacuolation, PLIN4-Related Myopathy
chr19 13333136 13333176 SCA6_CACNA1A CACNA1A CTG CTG 21 AD Spinocerebellar ataxia type 6
chr19 14622655 14622692 OPDM2_GIPC1 GIPC1 CCG CCG 73 AD Oculopharyngodistal myopathy type 2
chr19 18921630 18921645 EDM1-PSACH_COMP COMP GTC GTC 6 AD Multiple epiphyseal dysplasia, Pseudoachondroplasia
diff --git a/data/STRchive-disease-loci.hg19.bed b/data/STRchive-disease-loci.hg19.bed
index 144707fd..14cce72c 100644
--- a/data/STRchive-disease-loci.hg19.bed
+++ b/data/STRchive-disease-loci.hg19.bed
@@ -55,7 +55,7 @@ chr17 17711672 17711774 FAME8_RAI1 RAI1 TTTTA TTTCA 9 AD Familial adult myocloni
chr17 78120808 78120938 RCPS_EIF4A3 EIF4A3 CCTCGCTGTGCCGCTGCCGA CCTCGCTGTGCCGCTGCCGA 14 AR Richieri-Costa-Pereira syndrome
chr18 666891 667632 CPUM_TYMS TYMS GATGGT GATGGT 210 AR Congenital Progressive Universal Melanosis
chr18 53253384 53253460 FECD3_TCF4 TCF4 CAG CAG 51 AD Fuchs endothelial corneal dystrophy 3
-chr19 4510739 4513671 MRUPAV_PLIN4 PLIN4 TGGTGTCCACGCCGGTCTGGATGGTTCCTTTGGCCACATTCATGGCACCAGTCACCCCACTACAGACGGTGTCCTTGGTACCTGTTAGGACAGTCTTAC TGGTGTCCACGCCGGTCTGGATGGTTCCTTTGGCCACATTCATGGCACCAGTCACCCCACTACAGACGGTGTCCTTGGTACCTGTTAGGACAGTCTTAC 39 AD Myopathy with Rimmed Ubiquitin-Positive Autophagic Vacuolation, PLIN4-Related Myopathy
+chr19 4510739 4513671 MRUPAV_PLIN4 PLIN4 TGGTGTCCACGCCGGTCTGGATGGTTCCTTTGGCCACATTCATGGCACCAGTCACCCCACTACAGACGGTGTCCTTGGTACCTGTTAGGACAGTCTTAC TGGTGTCCACGCCGGTCTGGATGGTTCCTTTGGCCACATTCATGGCACCAGTCACCCCACTACAGACGGTGTCCTTGGTACCTGTTAGGACAGTCTTAC 37 AD Myopathy with Rimmed Ubiquitin-Positive Autophagic Vacuolation, PLIN4-Related Myopathy
chr19 13318672 13318712 SCA6_CACNA1A CACNA1A CTG CTG 21 AD Spinocerebellar ataxia type 6
chr19 14606853 14606887 OPDM2_GIPC1 GIPC1 CCG CCG 73 AD Oculopharyngodistal myopathy type 2
chr19 18896844 18896860 EDM1-PSACH_COMP COMP GTC GTC 6 AD Multiple epiphyseal dysplasia, Pseudoachondroplasia
diff --git a/data/STRchive-disease-loci.hg38.bed b/data/STRchive-disease-loci.hg38.bed
index 41df4596..a8e6d8fa 100644
--- a/data/STRchive-disease-loci.hg38.bed
+++ b/data/STRchive-disease-loci.hg38.bed
@@ -55,7 +55,7 @@ chr17 17808358 17808460 FAME8_RAI1 RAI1 TTTTA TTTCA 9 AD Familial adult myocloni
chr17 80147009 80147139 RCPS_EIF4A3 EIF4A3 CCTCGCTGTGCCGCTGCCGA CCTCGCTGTGCCGCTGCCGA 14 AR Richieri-Costa-Pereira syndrome
chr18 666891 667632 CPUM_TYMS TYMS GATGGT GATGGT 210 AR Congenital Progressive Universal Melanosis
chr18 55586153 55586229 FECD3_TCF4 TCF4 CAG CAG 51 AD Fuchs endothelial corneal dystrophy 3
-chr19 4510727 4513659 MRUPAV_PLIN4 PLIN4 TGGTGTCCACGCCGGTCTGGATGGTTCCTTTGGCCACATTCATGGCACCAGTCACCCCACTACAGACGGTGTCCTTGGTACCTGTTAGGACAGTCTTAC TGGTGTCCACGCCGGTCTGGATGGTTCCTTTGGCCACATTCATGGCACCAGTCACCCCACTACAGACGGTGTCCTTGGTACCTGTTAGGACAGTCTTAC 39 AD Myopathy with Rimmed Ubiquitin-Positive Autophagic Vacuolation, PLIN4-Related Myopathy
+chr19 4510727 4513659 MRUPAV_PLIN4 PLIN4 TGGTGTCCACGCCGGTCTGGATGGTTCCTTTGGCCACATTCATGGCACCAGTCACCCCACTACAGACGGTGTCCTTGGTACCTGTTAGGACAGTCTTAC TGGTGTCCACGCCGGTCTGGATGGTTCCTTTGGCCACATTCATGGCACCAGTCACCCCACTACAGACGGTGTCCTTGGTACCTGTTAGGACAGTCTTAC 37 AD Myopathy with Rimmed Ubiquitin-Positive Autophagic Vacuolation, PLIN4-Related Myopathy
chr19 13207858 13207898 SCA6_CACNA1A CACNA1A CTG CTG 21 AD Spinocerebellar ataxia type 6
chr19 14496041 14496075 OPDM2_GIPC1 GIPC1 CCG CCG 73 AD Oculopharyngodistal myopathy type 2
chr19 18786034 18786050 EDM1-PSACH_COMP COMP GTC GTC 6 AD Multiple epiphyseal dysplasia, Pseudoachondroplasia
diff --git a/data/STRchive-loci.json b/data/STRchive-loci.json
index e28d1699..5f04ca8e 100644
--- a/data/STRchive-loci.json
+++ b/data/STRchive-loci.json
@@ -295,7 +295,7 @@
"typ_age_onset_max": 0.0,
"novel": "ref",
"mechanism": "LoF",
- "mechanism_detail": "Polyalanine expansions lead to reduction in protein product through unclear mechanism [@pmid:36169768; @pmid:38467784]. Apparent aggregation and mis-localisation of mutan protein, increased with expansion length [@genereviews:NBK51932].",
+ "mechanism_detail": "Polyalanine expansions lead to reduction in protein product through unclear mechanism [@pmid:36169768; @pmid:38467784]. Apparent aggregation and mis-localisation of mutant protein, increased with expansion length [@genereviews:NBK51932].",
"source": [],
"details": "ARX expansions [@genereviews:NBK535148] result in a phenotypic spectrum of conditions including Partington syndrome [@omim:309510], Early Infantile Epileptic Encephalopathy [@omim:308350], Agenesis of Corpus Callosum with Abnormal Genitalia [@omim:300004], and X-Linked Lissencephaly with Ambiguous Genitalia [@omim:300215], described in the literature [@pmid:26029707; @pmid:20506206].",
"omim": ["308350", "300419", "300215"],
@@ -697,7 +697,7 @@
"webstr_hg38": ["5316666", "1481402"],
"webstr_hg19": ["Expansion_SCA3_MJD/ATXN3"],
"tr_atlas": ["TR132758"],
- "disease_description": "Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease, is the most common subtype of type 1 autosomal dominant cerebellar ataxia (ADCA type 1), a neurodegenerative disorder, and is characterized by ataxia, external progressive ophthalmoplegia, and other neurological manifestations [@mondo:0007182].",
+ "disease_description": "Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease, is the most common subtype of type 1 autosomal dominant cerebellar ataxia (ADCA type 1), a neurodegenerative disorder, and is characterized by ataxia, external progressive ophthalmoplegia, and other neurological manifestations [@mondo:0007182]. Research suggests that length of ATXN2 expansions may affect the phenotype of SCA3 [@pmid:40684213].",
"locus_tags": ["supported_evidence", "somatic_instability", "anticipation", "paternal_expansion", "maternal_expansion", "length_affects_onset", "length_affects_phenotype", "length_affects_severity"],
"disease_tags": ["spinocerebellar_ataxia"],
"references": ["genereviews:NBK1196", "pmid:40004498", "pmid:30414314", "pmid:36169768", "pmid:37906407", "pmid:35245110", "pmid:39731318", "pmid:39699045", "pmid:29100084", "genereviews:NBK557816", "pmid:7874163", "mondo:0007182"],
@@ -1577,7 +1577,7 @@
"mechanism": "LoF",
"mechanism_detail": "LoF from a hypomorphic allele [@pmid:24360810].",
"source": [],
- "details": "Complex repeat of 18-20 nucleotides expands to cause diease: disease is found in individuals with 14-16 repeats [@pmid:24360810], while controls have typically 3-12 repeats with as low as 1 repeat [@genereviews:NBK535148; @gnomad:EIF4A3]. Significance of intermediate alleles is unknown [@pmid:29112243].",
+ "details": "Complex repeat of 18-20 nucleotides expands to cause disease: disease is found in individuals with 14-16 repeats [@pmid:24360810], while controls have typically 3-12 repeats with as low as 1 repeat [@genereviews:NBK535148; @gnomad:EIF4A3]. Significance of intermediate alleles is unknown [@pmid:29112243].",
"omim": ["268305"],
"prevalence": null,
"prevalence_details": "49 cases as of Nov 2023 [@doi:10.1016/j.omsc.2023.100340]. Found in Brazilian families and one unrelated French patient [@mondo:0009998].",
@@ -1849,7 +1849,7 @@
"webstr_hg38": ["1509872"],
"webstr_hg19": [],
"tr_atlas": ["TR93516"],
- "disease_description": "Any Friedreich ataxia in which the cause of the disease is a mutation in the FXN gene [@mondo:0100340].",
+ "disease_description": "Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder characterized by progressive gait and limb ataxia with associated limb muscle weakness, absent lower limb reflexes, extensor plantar responses, dysarthria, and decreased vibratory sense and proprioception. Onset is usually in the first or second decade, before the end of puberty [@omim:229300].",
"locus_tags": ["supported_evidence", "somatic_instability", "maternal_expansion", "length_affects_onset", "length_affects_phenotype", "motif_affects_instability", "motif_affects_onset", "motif_affects_penetrance"],
"disease_tags": ["ataxia"],
"references": ["genereviews:NBK1281", "pmid:16205714", "pmid:36169768", "pmid:11748752", "pmid:8815938", "omim:229300", "pmid:29100084", "pmid:8596916", "mondo:0100340"],
@@ -3100,13 +3100,13 @@
"benign_max": 31.0,
"intermediate_min": null,
"intermediate_max": null,
- "pathogenic_min": 39.0,
+ "pathogenic_min": 37.0,
"pathogenic_max": 50.0,
"ref_copies": 31.0,
"motif_len": 99,
- "age_onset": "22-65 [@pmid:36151849; @pmid:37145156; @pmid:35499779].",
+ "age_onset": "22-66 [@pmid:36151849; @pmid:37145156; @pmid:35499779; @pmid:40693562].",
"age_onset_min": 22,
- "age_onset_max": 65,
+ "age_onset_max": 66,
"typ_age_onset_min": null,
"typ_age_onset_max": null,
"novel": "ref",
@@ -3116,7 +3116,7 @@
"details": "This is an expanded variable number tandem repeat (VNTR) in the PLIN4 gene, located in exon 3. This repeat consists of a 99 bp motif which encodes 33 amino-acids within the perilipin-4 protein [@pmid:32451610]. Expansions of this 99 bp motif leads to insertion of multiple imperfect 33–amino acid repeats. These repetitive sequences are thought to contribute to abnormal protein aggregation and dysregulated autophagy seen in affected muscle tissue [@omim:601846].",
"omim": ["601846"],
"prevalence": null,
- "prevalence_details": "Studied in patients of chinese ancestry [@pmid:36151849].",
+ "prevalence_details": "Studied in patients of chinese ancestry and two families of spanish ancestry [@pmid:36151849; @pmid:40693562].",
"stripy": [],
"gnomad": [],
"genereviews": [],
diff --git a/data/STRchive-loci.schema.json b/data/STRchive-loci.schema.json
index d891dc2f..cdc6a287 100644
--- a/data/STRchive-loci.schema.json
+++ b/data/STRchive-loci.schema.json
@@ -36,7 +36,7 @@
"type": [ "integer", "null" ]
},
"id": {
- "description": "Unique identifier for the locus within STRchive in the form [disease_id]_[gene] e.g. CANVAS_RFC1",
+ "description": "Unique identifier for the locus within STRchive in the form [disease_id]_[gene] e.g. CANVAS_RFC1. Additional characters may be added to the end of the ID to make it unique within STRchive, e.g. HFG_HOXA13-I, HFG_HOXA13-II",
"type": "string"
},
"disease_id": {
diff --git a/data/plots/age-onset.json b/data/plots/age-onset.json
index ed07056f..99f356fb 100644
--- a/data/plots/age-onset.json
+++ b/data/plots/age-onset.json
@@ -12,7 +12,7 @@
"offset": -0.1,
"orientation": "h",
"width": 0.2,
- "x": [47, 32, 39, 52, 51, 43, 66, 71, 59, 0, 52, 19, 46, 57, 25, 56, 0, 53, 54, 72, 36, 23, 68, 40, 20, 75, 54, 60, 0, 61, 59, 57, 0, 0, 47, 56, 59, 10, 70, 84, 0, 0, 1, 84, 6, 0, 0, 73, 76, 72, 74, 0, 65, 0, 0, 3, 36, 0, 0],
+ "x": [47, 32, 39, 52, 51, 44, 66, 71, 59, 0, 52, 19, 46, 57, 25, 56, 0, 53, 54, 72, 36, 23, 68, 40, 20, 75, 54, 60, 0, 61, 59, 57, 0, 0, 47, 56, 59, 10, 70, 84, 0, 0, 1, 84, 6, 0, 0, 73, 76, 72, 74, 0, 65, 0, 0, 3, 36, 0, 0],
"y": ["FECD3", "CJD", "SCA36", "ALS1", "FAME6", "MRUPAV", "SCA27B", "FTDALS1", "OPMD", "CANVAS", "ADTKD", "FAME7", "SCA37", "SCA6", "OPML1", "OPDM2", "XDP", "SCA4", "HDL2", "SCA10", "FAME3", "FAME4", "NIID", "OPDM5", "OPDM4", "SCA31", "SCA12", "FAME1", "SBMA", "FAME8", "OPDM1", "SCA1", "EPM1", "DMD", "SCA", "FAME2", "SCA17", "EDM1, PSACH", "SCA3, MJD", "SCA2", "FRDA", "GDPAG", "FRA7A", "HD", "FRA2A", "FRAXE", "NME", "DM2", "SCA8", "DRPLA", "DM1", "XLMR", "SCA7", "EIEE1", "PRTS", "FRA12A", "CCHS", "FXS, FXTAS, POF1", "HMNR7"],
"type": "bar"
},
diff --git a/data/plots/path-size.json b/data/plots/path-size.json
index bf86f9b2..97f9d9c2 100644
--- a/data/plots/path-size.json
+++ b/data/plots/path-size.json
@@ -33,7 +33,7 @@
"type": "bar"
},
{
- "base": [5000, 4000, 3955, 3900, 3861, 3300, 2040, 2000, 1506, 1370, 1350, 1260, 1000, 960, 900, 819, 603, 603, 550, 525, 483, 360, 360, 354, 303, 300, 300, 280, 255, 219, 216, 213, 210, 198, 180, 177, 168, 155, 153, 153, 150, 147, 144, 138, 135, 120, 120, 117, 114, 111, 108, 105, 78, 75, 75, 66, 66, 66, 66, 63, 60, 60, 54, 54, 51, 45, 45, 36, 36, 33, 18, 12, 10, 0],
+ "base": [5000, 4000, 3955, 3900, 3663, 3300, 2040, 2000, 1506, 1370, 1350, 1260, 1000, 960, 900, 819, 603, 603, 550, 525, 483, 360, 360, 354, 303, 300, 300, 280, 255, 219, 216, 213, 210, 198, 180, 177, 168, 155, 153, 153, 150, 147, 144, 138, 135, 120, 120, 117, 114, 111, 108, 105, 78, 75, 75, 66, 66, 66, 66, 63, 60, 60, 54, 54, 51, 45, 45, 36, 36, 33, 18, 12, 10, 0],
"hovertemplate": "Disease: %{y} \u003cbr\u003e Range: %{base} - %{x} bp",
"legendgroup": "Pathogenic",
"marker":
@@ -44,7 +44,7 @@
"offset": -0.3,
"orientation": "h",
"width": 0.6,
- "x": [0, 18500, 1220, 11100, 1089, 0, 2460, 11750, 23022, 1420, 0, 294, 0, 1851, 0, 99, 5397, 5397, 3250, 17875, 1617, 1140, 231, 1728, 597, 43700, 10700, 40, 612, 273, 114, 3687, 102, 1353, 81, 69, 4932, 220, 81, 7647, 11850, 51, 135, 84, 165, 60, 264, 156, 90, 1269, 642, 1395, 21, 0, 0, 0, 30, 3, 12, 36, 0, 21, 0, 3, 30, 27, 1625, 18, 0, 135, 3, 0, 20, 0],
+ "x": [0, 18500, 1220, 11100, 1287, 0, 2460, 11750, 23022, 1420, 0, 294, 0, 1851, 0, 99, 5397, 5397, 3250, 17875, 1617, 1140, 231, 1728, 597, 43700, 10700, 40, 612, 273, 114, 3687, 102, 1353, 81, 69, 4932, 220, 81, 7647, 11850, 51, 135, 84, 165, 60, 264, 156, 90, 1269, 642, 1395, 21, 0, 0, 0, 30, 3, 12, 36, 0, 21, 0, 3, 30, 27, 1625, 18, 0, 135, 3, 0, 20, 0],
"y": ["FAME4", "SCA10", "FAME3", "SCA36", "MRUPAV", "FAME6", "GDPAG", "CANVAS", "FTDALS1", "FAME2", "FRA7A", "CPUM", "NME", "SCA27B", "FRA2A", "FRA12A", "FRAXE", "FXS, FXTAS, POF1", "SCA31", "FAME1", "OPML1", "EPM1", "OPDM4", "OPDM5", "JBS", "DM2", "FAME7", "RCPS", "OPDM1", "OPDM2", "DBQD2, BSS", "SCA8", "XDP", "NIID", "SCA3, MJD", "DMD", "FRDA", "SCA37", "SCA12", "FECD3", "DM1", "SCA17", "DRPLA", "SCA4", "SCA", "HDL2", "CJD", "SCA1", "SBMA", "SCA7", "HD", "SCA2", "CCHS", "TOF", "HPE5", "HFG-I", "HFG-III", "SD5", "XLMR", "SCA6", "PRTS", "CCD", "HFG-II", "HSAN VIII", "EIEE1", "BPES", "FAME8", "OPMD", "VACTERLX", "ALS1", "EDM1, PSACH", "CHNG3", "HMNR7", "CPEO"],
"type": "bar"
},
@@ -96,7 +96,7 @@
},
"mode": "lines",
"showlegend": false,
- "x": [3069, 3861],
+ "x": [3069, 3663],
"y": ["MRUPAV", "MRUPAV"],
"type": "scatter"
},