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
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.