The molecular genetics of the spinocerebellar ataxias

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.