Genetic localization of the Ca2+ channel gene CACNG2 near SCA10 on chromosome 22q13

Purpose: Voltage-dependent calcium channel mutations have been associated w ith spinocerebellar ataxia in humans (SCA6) and with ataxia, progressive ce rebellar degeneration, and epilepsy in mice (tottering, lethargic, and star gazer). A novel autosomal dominant spinocerebellar ataxia syndrome with epi lepsy (SCA10) was recently mapped to chromosome 22q13. The human ortholog o f the mouse stargazer locus, the calcium channel gamma subunit gene CA CNG2 , also is located in this region. Because the phenotypes of stargazer mice and SCA10 patients were similar, consisting of both cerebellar ataxia and s eizures, we hypothesized that CACNG2 was a likely candidate for the SCA10 l ocus. Methods: Polymerase chain reaction (PCR) based assays were developed for tw o polymorphic microsatellite markers near CACNG2. The location of CACNG2 wa s determined by linkage and haplotype analysis of the genotypes of 22 indiv iduals from a human pedigree segregating SCA10. Results: SCA10 was previously localized distal to marker D22S1177 on chromo some 22q13. We determined that CACNG2 was linked to D22S283 and D22S1177 wi th the marker order: centromere-D22S283-bcmDLB1 (CACNG2)-D22S1177-D22S423-t elomere. Thus CA CNG2 is located proximal to the SCA10 recombinant interval . Conclusions: Here we report the first genetic linkage of CACNG2 on chromoso me 22q13 and exclude it as a candidate for SCA10. In addition, our data cla rify the relation between the physical and genetic linkage maps of this reg ion and will facilitate isolation of the SCA10 gene.