Document Detail

Unstable triplet repeat and phenotypic variability of spinocerebellar ataxia type 1.
MedLine Citation:
PMID:  8619528     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article    
Journal Detail:
Title:  Annals of neurology     Volume:  39     ISSN:  0364-5134     ISO Abbreviation:  Ann. Neurol.     Publication Date:  1996 Apr 
Date Detail:
Created Date:  1996-06-11     Completed Date:  1996-06-11     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7707449     Medline TA:  Ann Neurol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  500-6     Citation Subset:  IM    
Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, Bethesda, MD USA.
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MeSH Terms
Age of Onset
Base Sequence
Chromosome Mapping
Genetic Variation*
Molecular Probes / genetics
Molecular Sequence Data
Nervous System Diseases / epidemiology,  genetics
Reference Values
Siberia / epidemiology
Spinocerebellar Degenerations / epidemiology,  genetics*,  physiopathology
Trinucleotide Repeats*
Reg. No./Substance:
0/Molecular Probes

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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