SCA6 MUTATION ANALYSIS IN A LARGE COHORT OF THE JAPANESE PATIENTS WITH LATE-ONSET PURE CEREBELLAR-ATAXIA

Spinocerebellar ataxia type 6 (SCA6) is caused by small CAG repeat exp ansion in the gene encoding the alpha(1A)-voltage-dependent-calcium ch annel subunit (CACNL1A4) on chromosome 19p13, and is a subgroup of the late-onset pure cerebellar ataxia (ADCA III). To investigate the prev alence of SCAB in the Japanese, we analyzed this mutation in 23 famili es and 12 probands with ADCA m. The specificity and stability of the C AG repeat were examined in additional individuals and families with ot her miscellaneous dominant SCAs. The CAG expansion of SCA6 gene was ex clusively observed in 12 of 23 families (52%) and 12 proband cases wit h ADCA III, but not in others. The CAG repeat was 21-33 in the disease -associated alleles (n = 56), and 4-18 in normal alleles (n = 1148). E xpanded alleles were stable during transmission, and a significant inv erse correlation for CAG repeat number with age at onset was noted. Ou r results indicate that SCA6 shares approximately half of the ADCA III in the Japanese, and that gene mutations causing the remaining, have yet to be identified. (C) 1998 Elsevier Science B.V.