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PMID: 8037204 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Molecular and clinical correlations in spinocerebellar ataxia type I: evidence for familial effects on the age at onset.

American journal of human genetics ·Vol. 55 ·No. 2 ·1994-08-00 ·Pages 244-52

Ranum LP, Chung MY, Banfi S, Bryer A, Schut LJ, Ramesar R, Duvick LA, McCall A, Subramony SH, Goldfarb L

Abstract

The spinocerebellar ataxias are a group of debilitating neurodegenerative diseases for which a clinical classification system has proved unreliable. We have recently isolated the gene for spinocerebellar ataxia type 1 (SCA1) and have shown that the disease is caused by an expanded, unstable, CAG trinucleotide repeat within an expressed gene. Normal alleles have a size range of 19-36 repeats, while SCA1 alleles have 42-81 repeats. In this study, we examined the frequency and variability of the SCA1 repeat expansion in 87 kindreds with diverse ethnic backgrounds and dominantly inherited ataxia. All nine families for which linkage to the SCA1 region of 6p had previously been established showed repeat expansion, while 3 of the remaining 78 showed a similar abnormality. For 113 patients from the families with repeat expansion, inverse correlations between CAG repeat size and both age at onset and disease duration were observed. Repeat size accounted for 66% of the variation in age at onset in these patients. After correction for repeat size, interfamilial differences in age at onset remained significant, suggesting that additional genetic factors affect the expression of the SCA1 gene product.

Related Genes
SCA1
MeSH Terms
Adolescent Age of Onset Base Sequence Child Chromosomes, Human, Pair 6 DNA/analysis DNA Primers Family Health Female Gene Expression Genes, Dominant Humans Linear Models Male Middle Aged Molecular Sequence Data Multivariate Analysis Phenotype Polymerase Chain Reaction Repetitive Sequences, Nucleic Acid/genetics Spinocerebellar Degenerations/genetics,pathology
Chemicals
DNA Primers DNA
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Ranum L P
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis.
Chung M Y
Banfi S
Bryer A
Schut L J
Ramesar R
Duvick L A
McCall A
Subramony S H
Goldfarb L
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
Published
1994-08-00
Pages
244-52
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1918367
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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