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.