The molecular genetics of the spinocerebellar ataxias

Abstract

The spinocerebellar ataxias (SCA) are a group of autosomal dominantly inherited ataxias that are clinically characterised by progressive ataxia. Until now, 13 genetically distinct SCA subtypes have been identified. In 5 of these disorders (SCA1, SCA2, SCA3, SCA6, SCA7), the mutation is a translated, expanded CAG repeat. SCA8 is caused by a CTG expansion in the 3′ untranslated region, SCA10 by an intronic pentanucleotide repeat expansion, and SCA12 by a CAG repeat expansion in the 5′ untranslated region of the respective genes. In all other SCAs, the mutations remain unknown. In most SCAs, ataxia is not an isolated symptom, but occurs in combination with a variety of non-cerebellar symptoms. In contrast, SCA5, SCA6, SCA8, SCA11 and SCA14 are characterised by an almost purely cerebellar phenotype.