ANALYSIS OF SPINOCEREBELLAR ATAXIA TYPE-1 (SCA1)-RELATED CAG TRINUCLEOTIDE EXPANSION IN JAPAN

Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disorder c aused by expansion of a CAG trinucleotide repeat. We analyzed CAG repe at expansion in 25 families in the northeast of Japan with hereditary ataxia of Menzel type. Twenty of 38 patients in 12 families had expand ed allele for SCA1. The number of CAG repeats correlated with the age at onset. Although the relationship between anticipation and the numbe r of CAG repeats in successive generations was not ascertainable, ther e was a tendency to paternal bias for the accelerated age at onset. St udy of the number of CAG repeats in various tissues showed no differen ces in the repeat length in lymphocytes, muscle, or brain; sperm, howe ver, showed an obvious expansion. This may be a clue to a possible mec hanism for the molecular basis of paternal anticipation of the disease . The SCAI gene was transcribed from both wild and mutated alleles in muscles of affected individuals, but the repeat length was the same fo r both the muscle cDNA and the lymphocyte genomic DNA. These results s uggest that, in the area of Japan where SCA1 is prevalent, 48% of fami lies with spinocerebellar degeneration have SCA1 mutation.