SPINOCEREBELLAR ATAXIA TYPE 6 - MOLECULAR AND CLINICAL-FEATURES OF 35JAPANESE PATIENTS INCLUDING ONE HOMOZYGOUS FOR THE CAG REPEAT EXPANSION

Spinocerebellar ataxia type 6 (SCAG) is a newly classified autosomal-d ominant cerebellar ataxia (ADCA) associated with CAG repeat expansion. We screened 111 patients with cerebellar ataxia for the SCAG mutation . Of these, 35 patients were found to have expanded CAG repeats in the SCAG gene, indicating that second to SCA3, SCAG is the most common AD CA in Japan. Expanded alleles ranged from 21 to 29 repeats, whereas no rmal alleles had seven to 17 repeats. There was no change in the CAG r epeat length during meiosis. The age at onset was inversely correlated with the repeat length. The main clinical feature of the 35 patients with SCAG was slowly progressive cerebellar ataxia; multisystem involv ement was not common. The 35 patients included nine cases without appa rent family history of cerebellar ataxia. The sporadic cases had small er CAG repeats (21 or 22 repeats) and a later age at onset (64.9 +/- 4 .9 years) than the other cases with established family history. We als o identified one patient who was homozygous for the SCA6 repeat expans ion. The homozygote showed an earlier age of onset and more severe cli nical manifestations than her sister, a heterozygote carrying an expan ded allele with the same repeat length as the homozygote. This finding suggests that the dosage of the CAG repeat expansion plays an importa nt role in phenotypic expression in SCA6.