Large expansion of the ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10

Spinocerebellar ataxia type 10 (SCA10; MIM 603516; refs 1.2) is an autosoma l dominant disorder characterized by cerebellar ataxia and seizures. The ge ne SCA10 maps to a 3.8-cM interval on human chromosome 22q13-qter (refs 1.2 ). Because several other SCA subtypes show trinucleotide repeat expansions, we examined microsatellites in this region. We found an expansion of a pen tanucleotide (ATTCT) repeat in intron 9 of SCA10 in all patients in five Me xican SCA10 families. There was an inverse correlation between the expansio n size, up to 22.5 kb larger than the normal allele, and the age of onset ( r(2)=0.34, P=0.018). Analysis of 562 chromosomes from unaffected individual s of various ethnic origins (including 242 chromosomes from Mexican persons ) showed a range of 10 to 22 ATTCT repeats with no evidence of expansions. Our data indicate that the new SCA10 intronic ATTCT pentanucleotide repeat in SCA10 patients is unstable and represents the largest microsatellite exp ansion found so far in the human genome.