Meiotic instability of the CAG repeats in the SCA6/CACNA1A gene in two Japanese SCA6 families

Intergenerational stability of the CAG repeat number has been considered to be a specific molecular feature of SCA6 compared with other CAG repeat dis eases. Nevertheless, we showed meiotic instability of the CAG repeats in th e SCA6/CACNLIA gene in two Japanese SCA6 families, including de novo expans ion. In one family. the CAG(20) allele expanded to the CAG(26) one during p aternal transmission, and in the other family, the CAG(19) allele expanded to the CAG(20) one during maternal transmission. Although it is controversi al as to whether the CAG(20) allele is pathological or not, this is the fir st case of haplotype analysis-proven de novo expansion in SCA6, confirming the derivation of an expanded allele from one normal allele. We should care fully follow up the individuals carrying the CAG(20) allele in our family w ho show normal neurological and radiological findings at present. (C) 2001 Elsevier Science B.V. All rights reserved.