Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the α(1A)-voltage-dependent calcium channel

Olga Zhuchenko, Jennifer Bailey, Penelope Bonnen, Tetsuo Ashizawa, David W. Stockton, Chris Amos, William B. Dobyns, S. H. Subramony, Huda Y. Zoghbi, Cheng Chi Lee

Research output: Contribution to journalReview articlepeer-review

1344 Scopus citations

Abstract

A polymorphic CAG repeat was identified in the human α(1A) voltage- dependent calcium channel subunit. To test the hypothesis that expansion of this CAG repeat could be the cause of an inherited progressive ataxia, we genotyped a large number of unrelated controls and ataxia patients. Eight unrelated patients with late onset ataxia had alleles with larger repeat numbers (21-27) compared to the number of repeats (4-16) in 475 non-ataxia individuals. Analysis of the repeat length in families of the affected individuals revealed that the expansion segregated with the phenotype in every patient. We identified six isoforms of the human α(1A) calcium channel subunit. The CAG repeat is within 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 α(1A) calcium channel is most likely the cause of a newly classified autosomal dominant spinocerebellar ataxia, SCA6.

Original languageEnglish (US)
Pages (from-to)62-69
Number of pages8
JournalNature Genetics
Volume15
Issue number1
DOIs
StatePublished - Jan 1997

Fingerprint Dive into the research topics of 'Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the α(1A)-voltage-dependent calcium channel'. Together they form a unique fingerprint.

Cite this