THE GENE FOR AUTOSOMAL-DOMINANT CEREBELLAR-ATAXIA TYPE-II IS LOCATED IN A 5-CM REGION IN 3P12-P13 - GENETIC AND PHYSICAL MAPPING OF THE SCA7 LOCUS

Two families with autosomal dominant cerebellar ataxia with pigmentary macular dystrophy (ADCA typo II) were investigated. analysis of 23 pa rent-child couples demonstrated the existence of marked anticipation, greater in paternal Than in maternal transmissions, with earlier age a t onset and a more rapid clinical course in successive generations. Cl inical analysis revealed the presence of a great variability in age at onset, initial symptom, and associated signs, confirming the characte ristic clinical heterogeneity of ADCA type II. The gene for ADCA type II previously was mapped to the spinocerebellar ataxia 7 (SCA7) locus on chromosome 3p12-p21.1. Linkage analysis of the two new families of different geographic origin confirmed the characteristic genetic homog eneity of ADCA type III distinguishing it from ADCA type I. Haplotype analysis permitted refinement of the SCA7 region to the 5-cM interval bet seen markers D3S1312 and D3S1600 on chromosome 3p12-p13. Eighteen sequence-tagged sites were used for the construction of an integrated map of the candidate region, based on a YACs contig. The entire candid ate region is contained in a single non-chimeric YAC of 660 kb. The pr obable involvement of a CAG trinucleotide expansion, suggested by prev ious studies, should greatly facilitate the identification of tile gen e for ADCA type II.