Genetic typing of the largest known Siberian kindred with autosomal dominant cerebellar ataxia has been completed. Nine alleles were identified in this kindred at the D6S89 locus and 5 alleles at the D6S274 locus of chromosome 6p. The affected individuals in 5 of 7 separate pedigrees carry D6S89 allele~4, and 2 pedigrees apparently had a recombination between the previously identified SCA1 gene locus and this telomeric marker. No recombination was observed between the SCA1 gene locus and the centromerically located microsatellite D6S274; the affected members of all 7 families carry the same D6S274~allele~3. The D6S274~allele~3~D6S89 allele~4 haplotype was detected in all affected individuals. These data suggest that there is significant linkage between the disorder and both markers, and that ataxia in this Siberian kindred is linked to the SCA1 gene on chromosome 6p. The mutation has been identified as a CAG trinucleotide repeat expansion within the SCA1 coding region. This result opens wide prospectives for clinical, preclinical and prenatal testing in the Siberian kindred, as well as in American families with ataxia. We estimated the effects of buspirone, a selective 5~HT1A serotonin receptor agonist, for symptomatic treatment in 16 patients with cerebellar ataxia. The patients took 60 mg~day of buspirone for 7 weeks. The results were assessed by weekly clinical rating, self~assessment rating, motor performance and posturography. We concluded that buspirone may be effective in symptomatic treatment of mild to moderate cerebellar ataxia and that a double~blind placebo~controlled study is now appropriate. Experimental characterization of expressed serotonergic receptors using a number of pharmacological agents, including buspirone, is currently in progress. A large Virginia family with essential tremor combined with focal dystonia in some family members is under genetic study to find the chromosome location for genes involved in this disorder.
