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

TitleAutosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel.
Publication TypeJournal Article
Year of Publication1997
AuthorsZhuchenko, O, Bailey, J, Bonnen, P, Ashizawa, T, Stockton, DW, Amos, C, Dobyns, WB, Subramony, SH, Zoghbi, HY, Lee, CC
JournalNat Genet
Volume15
Issue1
Pagination62-9
Date Published1997 Jan
ISSN1061-4036
KeywordsAlleles, Amino Acid Sequence, Animals, Calcium Channels, Cerebellar Ataxia, Female, Genes, Dominant, Genotype, Humans, Male, Molecular Sequence Data, Mutation, Nerve Tissue Proteins, Pedigree, Peptides, Rabbits, Sequence Homology, Amino Acid, Trinucleotide Repeats
Abstract

A polymorphic CAG repeat was identified in the human alpha 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 alpha 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 alpha 1A calcium channel is most likely the cause of a newly classified autosomal dominant spinocerebellar ataxia, SCA6.

DOI10.1038/ng0197-62
Alternate JournalNat. Genet.
PubMed ID8988170
Grant ListNS27699 / NS / NINDS NIH HHS / United States