CLONING OF THE GENE FOR SPINOCEREBELLAR ATAXIA-2 REVEALS A LOCUS WITHHIGH-SENSITIVITY TO EXPANDED CAG GLUTAMINE REPEATS/

Two forms of the neurodegenerative disorder spinocerebellar ataxia are known to be caused by the expansion of a CAG (polyglutamine) trinucle otide repeat. By screening cDNA expression libraries, using an antibod y specific for polyglutamine repeats, we identified six novel genes co ntaining CAG stretches. One of them is mutated in patients with spinoc erebellar ataxia linked to chromosome 12q (SCA2). This gene shows ubiq uitous expression and encodes a protein of unknown function. Normal SC A2 alleles (17 to 29 CAG repeats) contain one to three CAAs in the rep eat. Mutated alleles (37 to 50 repeats) appear particularly unstable, upon both paternal and maternal transmissions. The sequence of three o f them revealed pure CAG stretches. The steep inverse correlation betw een age of onset and CAG number suggests a higher sensitivity to polyg lutamine length than in the other polyglutamine expansion diseases.