REFINEMENT BY LINKAGE ANALYSIS IN 2 LARGE FAMILIES OF THE CANDIDATE REGION OF THE 3RD LOCUS (SCA3) FOR AUTOSOMAL-DOMINANT CEREBELLAR-ATAXIATYPE-I

The autosomal dominant cerebellar ataxias (ADCA) are clinically and ge netically heterogeneous. To date, several loci (SCAI-V) have been iden tified for ADCA type I. We have studied two large families from the no rthern part of The Netherlands with ADCA type I with a broad intra-fam ilial variation of symptoms. In both families significant linkage is s hown of the disease to the markers of the SCA3 locus on chromosome 14. Through recombinations, the candidate region for SCA3 could be refine d to a 13-cM range between D14S256 and D14S81. No recombinations were detected with the markers D14S291 and D14S280, which suggests that the SCA3 gene lies close to these loci. This finding will benefit the ind ividuals at risk in these two families who are seeking predictive test ing or prenatal diagnosis.