| Unstable triplet repeat and phenotypic variability of spinocerebellar ataxia type 1. | |
MedLine Citation:
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PMID: 8619528 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A Siberian kindred with spinocerebellar ataxia genetically linked to the SCA1 locus on chromosome 6p has been screened for the CAG triplet expansion within the coding region of the SCA1 gene. The kindred includes 1,484 individuals, 225 affected and 656 at risk, making this collection the largest spinocerebellar ataxia type 1 (SCA1) pedigree known. Each of the studied 78 SCA1 patients carried an expanded allele containing a stretch of 39 to 72 uninterrupted CAG repeats. Normal alleles had 25 to 37 trinucleotide repeats. Expanded alleles containing 40 to 55 repeats were found in 26 at-risk relatives. The number of CAG repeats in the mutated allele was inversely correlated with age at disease onset. Cerebellar deficiency was present in each patient and its severity was moderately affected by the number of CAG repeats. In contrast, the associated signs, dysphagia, diffuse skeletal muscle atrophy with fasciculations, and tongue atrophy were absent or mild in patients with low CAG repeat numbers, but severely complicated the course of illness in patients with a larger number of repeat units. One female mutation carrier was asymptomatic at age 66, more than 2 standard deviations beyond the average age of risk, suggesting incomplete penetrance. In 2 symptomatic individuals who had an expanded number of CAG repeats on both chromosomes, age at onset, rate of progression, and clinical manifestation corresponded to the size of the larger allele. |
Authors:
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L G Goldfarb; O Vasconcelos; F A Platonov; A Lunkes; V Kipnis; S Kononova; T Chabrashvili; V A Vladimirtsev; V P Alexeev; D C Gajdusek |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Annals of neurology Volume: 39 ISSN: 0364-5134 ISO Abbreviation: Ann. Neurol. Publication Date: 1996 Apr |
Date Detail:
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Created Date: 1996-06-11 Completed Date: 1996-06-11 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 7707449 Medline TA: Ann Neurol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 500-6 Citation Subset: IM |
Affiliation:
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Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, Bethesda, MD USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Age of Onset Aged Alleles Base Sequence Chromosome Mapping Female Genetic Variation* Homozygote Humans Male Molecular Probes / genetics Molecular Sequence Data Nervous System Diseases / epidemiology, genetics Phenotype Reference Values Siberia / epidemiology Spinocerebellar Degenerations / epidemiology, genetics*, physiopathology Trinucleotide Repeats* |
| Chemical | |
Reg. No./Substance:
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0/Molecular Probes |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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