[Clinical and genetic characteristics of SCA1]

Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disorder caused by expansion of a CAG trinucleotide repeat. We analyzed CAG repeat expansion in 25 families with hereditary ataxia of Menzel type in the northeast of Japan. Twenty of 38 patients in 12 families had expanded allele for SCA1. The number of CAG repeats correlated with the age at onset. Although the relationship between anticipation and the number of CAG repeats in successive generations was not ascertainable, there was a tendency to paternal bias for the accelerated age at onset. Study of the number of CAG repeats in various tissues showed no differences in the repeat length in lymphocytes, muscle or brain; sperm, however, showed an obvious expansion. This may be a clue to a possible mechanism for the molecular basis of paternal anticipation of the disease. These results suggest that, in the area of Japan in which SCA1 is prevalent, 48% of families with spinocerebellar degeneration have SCA1 mutation.