Document Detail


Unstable triplet repeat and phenotypic variability of spinocerebellar ataxia type 1.
MedLine Citation:
PMID:  8619528     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
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
Related Documents :
15258188 - Fluorescence in situ hybridization analysis reveals multiple loci of knob-associated dn...
20457068 - Withdrawn: development and characterization of two mini-x chromosomal short tandem repe...
15998728 - Two hybridization events define the population structure of trypanosoma cruzi.
1824668 - Use of short sequence repeat dna polymorphisms after pcr amplification to detect the pa...
12818528 - Disease associated balanced chromosome rearrangements (dbcr): report of two new cases.
22162288 - Etv6 rearrangements are recurrent in myeloid malignancies and are frequently associated...
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    
Affiliation:
Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, Bethesda, MD USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
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:
0/Molecular Probes

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


Previous Document:  Spinocerebellar ataxia 3 and Machado-Joseph disease: clinical, molecular, and neuropathological feat...
Next Document:  Chromosome 12-linked autosomal dominant scapuloperoneal muscular dystrophy.