SPINOCEREBELLAR ATAXIA TYPE-2 - GENOTYPE AND PHENOTYPE IN GERMAN KINDREDS

Background: Spinocerebellar ataxia type 2 (SCA2) is an autosomal domin ant cerebellar ataxia (ADCA) for which the disease-causing mutation ha s recently been characterized as an expanded CAG trinucleotide repeat. We investigated 64 families of German ancestry with ADCA and 55 patie nts with sporadic ataxia for the SCA2 mutation. Results: Expanded alle les were found in 6 of the 64 families and in 1 patient with sporadic ataxia. This patient had a de novo mutation from an intermediate pater nal allele. Length of repeats in 21 patients with SCA2. ranged from 36 to 52 CAG motifs and was inversely correlated with age at onset and p rogression of the disease. Expanded alleles were unstable during meios is; paternal transmission especially caused significant anticipation o f onset up to 26 years earlier. The SCA2 phenotype differed from those of SCA1 and SCA3 with higher frequencies of slowed ocular movements, postural and action tremor, myoclonus, and hyporeflexia. However, no s ingle feature was sufficient to permit a specific clinical diagnosis. Conclusions: Spinocerebellar ataxia type 2 accounts for about 10% of G erman families with ADCA but may also be present in sporadic ataxia du e to de novo mutations. Clinical features are highly variable among an d even within families. However, the size of the expanded repeat influ ences the phenotype and is relevant for course and prognosis of the di sease.