Trinucleotide Repeats in 202 Families With Ataxia

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Abstract
THE SPINOCEREBELLAR ataxias (SCAs) are neurodegenerative disorders that are clinically and genetically heterogeneous. Ten genetically different SCAs are known to be caused by trinucleotide repeat (TNR) expansions. In the dominant SCAs, the mutant proteins show an expanded polyglutamine tract in SCA1, SCA2, Machado-Joseph disease (MJD), SCA6, SCA7, and dentatorubropallidoluysian atrophy (DRPLA),1-9 whereas SCA8 and SCA12 are caused by untranslated (CTG)n and (CAG)n expansions, respectively.10,11 In Friedreich ataxia (FRDA), the mutant protein is deficient in homozygotes for a (GAA)n expansion in intron 1 of the FRDA gene.12 Recently, an expanded CAG repeat tract has been found at the TATA-binding protein gene (TBP) in an isolated patient with symptoms of ataxia and intellectual deterioration.13TBP repeat expansions have since been described in 4 Japanese families affected by a new type of ataxia with dementia named SCA17.14 Matsuura et al15 found a large expansion of pentanucleotide (ATTCT)n in intron 9 of the SCA10 gene in patients with spinocerebellar ataxia type 10, thus being the first to show the existence of a new class of dynamic mutations.