Analysis of the polymorphic SCA37 locus in a cohort of 167 Japanese patients with degenerative ataxia

Abstract

A number of dominantly inherited neurodegen- erative disorders have been attributed to abnor- mal expansions of microsatellites. The mutation causing spinocerebellar ataxia type 37 (SCA37) has recently been identified as an insertion of an expanded ATTTC repeat into a polymorphic locus where a short repeat of ATTTT is usually observed. To clarify variations at the SCA37 locus in the Jap- anese population, genomic DNA samples of a cohort of 167 patients with degenerative ataxic disorders were analyzed. Repeat length was evaluated with polymerase chain reaction and resequencing at the SCA37 locus. We found that the majority (96.4%) of alleles were within the range between 8 and 17 ATTTT repeats. Short expansions consisting of fewer than 40 repeats of ATTTT were identified in 12 alleles (3.6%), but neither long ATTTT repeat expansions nor ATTTC repeat were observed. The most commonly observed alleles were 12 and 13 repeats of ATTTT, with frequencies of 38.3% and 40.1%, respectively. The present study clarified allele frequencies of the polymorphic SCA37 locus in Japanese patients with ataxic disorders. Long expansions of ATTTT repeats appeared to be extremely rare, which may be one of the reasons for the observed scarcity of SCA37 in Japan.