Spinocerebellar Ataxia 10 (SCA10)

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative disease characterized by ataxia and epilepsy. Within a given family, the disease typically shows progressively earlier onset of the disease in successive generations with increasing severity, a phenomenon known as anticipation. The combination of relatively pure cerebellar ataxia and epilepsy is unique among inherited ataxias. The clinical diagnosis of SCA10 can be suspected based on this unique clinical feature, especially in families of Mexican descent in which SCA10 appears to be prevalent. In SCA10, the mutation is a very large expansion of an unstable ATTCT pentanucleotide repeat in intron 9 of the SCA10 gene. Thus, trinucleotide repeats are the sole class of microsatellite repeats whose expansions cause inherited ataxias, until the discovery of pentanucleotide repeat expansion in SCA10. SCA10 is the only human disease caused by expansion of a pentanucleotide repeat. This chapter presents a synoptic view of clinical features and molecular genetics of this disease, and discusses potential pathogenic mechanisms of SCA10.