A 3RD LOCUS FOR AUTOSOMAL-DOMINANT CEREBELLAR-ATAXIA TYPE-I MAPS TO CHROMOSOME 14Q24.3-QTER - EVIDENCE FOR THE EXISTENCE OF A 4TH LOCUS

The autosomal dominant cerebellar ataxias (ADCA) type I are a group of neurological disorders that are clinically and genetically heterogene ous. Two genes implicated in the disease, SCA1 (spinal cerebellar atax ia 1) and SCA2, are already localized. We have mapped a third locus to chromosome 14q24.3-qter, by linkage analysis in a non-SCA1/non-SCA2 f amily and have confirmed its existence in a second such family. We sug gest designating this new locus ''SCA3.'' Combined analysis of the two families restricted the SCA3 locus to a 15-cM interval between marker s D14S67 and D14S81. The gene for Machado-Joseph disease (MJD), a clin ically different form of ADCA type I, has been recently assigned to ch romosome 14q24.3-q32. Although the SCA3 locus is within the MJD region , linkage analyses cannot yet demonstrate whether they result from mut ations of the same gene. Linkage to all three loci (SCA1, SCA2, and SC A3) was excluded in another family, which indicates the existence of a fourth ADCA type I locus.