Mapping of a new autosomal dominant spinocerebellar ataxia to chromosome 22

The autosomal dominant cerebellar ataxias (ADCAs) are a clinically and gene tically heterogeneous group of disorders. The clinical symptoms include cer ebellar dysfunction and associated signs from dysfunction in other parts of the nervous system. So far, five spinocerebellar ataxia (SCA) genes have b een identified: SCA1, SCA2, SCA3, SCA6, and SCA7. Loci for SCA4 and SCA5 ha ve been mapped. However, approximately one-third of SCAs have remained unas signed. We have identified a Mexican American pedigree that segregates a ne w form of ataxia clinically characterized by gait and limb ataxia, dysarthr ia, and nystagmus. Two individuals have seizures. After excluding all known genetic loci for linkage, we performed a genomewide search and identified linkage to a 15-cM region on chromosome 22q13. A maximum LOD score of 4.3 ( recombination fraction 0) was obtained for D22S928 and D22S1161. This disti nct form of ataxia has been designated "SCA10." Anticipation was observed i n the available parent-child pairs, suggesting that trinucleotide-repeat ex pansion may be the mutagenic mechanism.