AUTOSOMAL-DOMINANT CEREBELLAR-ATAXIA (SCA6) ASSOCIATED WITH SMALL POLYGLUTAMINE EXPANSIONS IN THE ALPHA(1A)-VOLTAGE-DEPENDENT CALCIUM-CHANNEL

Citation
O. Zhuchenko et al., AUTOSOMAL-DOMINANT CEREBELLAR-ATAXIA (SCA6) ASSOCIATED WITH SMALL POLYGLUTAMINE EXPANSIONS IN THE ALPHA(1A)-VOLTAGE-DEPENDENT CALCIUM-CHANNEL, Nature genetics, 15(1), 1997, pp. 62-69
Citations number
44
Categorie Soggetti
Genetics & Heredity
Journal title
ISSN journal
10614036
Volume
15
Issue
1
Year of publication
1997
Pages
62 - 69
Database
ISI
SICI code
1061-4036(1997)15:1<62:AC(AWS>2.0.ZU;2-#
Abstract
A polymorphic CAG repeat was identified in the human alpha(1A) voltage -dependent calcium channel subunit, To test the hypothesis that expans ion of this CAG repeat could be the cause of an inherited progressive ataxia, we genotyped a large number of unrelated controls and ataxia p atients. Eight unrelated patients with late onset ataxia had alleles w ith larger repeat numbers (21-27) compared to the number of repeats (4 -16) in 475 non-ataxia individuals, Analysis of the repeat length in f amilies of the affected individuals revealed that the expansion segreg ated with the phenotype in every patient, We identified six isoforms o f the human alpha(1A) calcium channel subunit. The CBG repeat is withi n the open reading frame and is predicted to encode glutamine in three of the isoforms. We conclude that a small polyglutamine expansion in the human alpha(1A) calcium channel is most likely the cause of a newl y classified autosomal dominant spinocerebellar ataxia, SCAG.