A gene on SCA4 locus causes dominantly inherited pure cerebellar ataxia

Background: Several different genes or their loci have been identified for autosomal dominant cerebellar ataxia (ADCA). However, other types of ataxia remain unassigned. Objective: To identify a new locus for ADCA. Methods: S ix Japanese families with ADCA with pure cerebellar syndrome (ADCA type III ) were examined. These families had been molecularly excluded for spinocere bellar ataxia (SCA) types 1 through 3, 5 through 8, and 10. Clinical examin ation was undertaken, and a genome-wide linkage search was performed on 250 microsatellite DNA markers. Results: Strong evidence for linkage was found with markers on human chromosome 16q, and haplotype and multipoint analyse s further refined the gene locus in a 10.9-cM interval between D16S3089 and D16S515. Linkage disequilibrium was further found with the marker D16S3107 within the interval. The locus was exactly the candidate interval of SCA4, a rare form of ADCA clinically characterized by ataxia with sensory neurop athy anti pyramidal tract signs. This would suggest that SCA4 and our ADCA type III are likely to be allelic disorders with different clinical feature s. Conclusion: The current study provides evidence that a gene on the SCA4 locus causes a pure cerebellar syndrome.