The expansion of the CAG repeat in ataxin-2 is a frequent cause of autosomal dominant spinocerebellar ataxia.

The autosomal dominant spinocerebellar ataxias (ADSCAs) are a heterogeneous group of late-onset neurodegenerative disorders with overlapping clinical features. Genetic linkage studies have identified at least seven distinct loci for the ADSCAs, allowing the genetic classification of these disorders. The spinocerebellar ataxia type 2 (SCA2) locus was mapped to chromosome 12, and a gene responsible for this disorder was recently isolated. The mutation causing SCA2 is an expansion of a trinucleotide CAG repeat contained within the coding region of a novel gene. We describe the results of genotypic analysis for the SCA2 repeat in individuals with ADSCA who were previously found negative for CAG repeat expansions in the SCA1, SCA3, or SCA6 genes. The expanded CAG repeat has been identified in 15 independent families. Repeat instability and anticipation were observed in two large kindreds. The SCA2 mutation was found in 18% of our ADSCA kindreds, confirming the high proportion of SCA2 among this group of disorders.