DOMINANTLY INHERITED CEREBELLO-OLIVARY ATROPHY IS NOT DUE TO A MUTATION AT THE SPINOCEREBELLAR ATAXIA-I, MACHADO-JOSEPH DISEASE, OR DENTATO-RUBRO-PALLIDO-LUYSIAN ATROPHY LOCUS

The dominantly inherited ataxias are characterized both by phenotypic variability (phenotypic heterogeneity) within the same genotype and ov erlapping phenotypes from different genotypes (genotypic heterogeneity ). Therefore it is important to characterize specific clinical-neuropa thologic phenotypes as precisely as possible at the genetic level. We describe a family with dominantly inherited ataxia of late adult onset with relatively ''pure'' cerebellar signs. Neuropathologic examinatio n in two individuals from this family revealed findings consistent wit h cerebello-olivary atrophy, suggesting that this neuropathologic phen otype may run true within families, Mutations at the spinocerebellar a taxia-I, Machado-Joseph disease, and dentatorubropallidoluysian atroph y loci were excluded by direct DNA analysis on the leukocytes of one l iving affected member. Thus we provide evidence that these mutations a re not responsible for this particular phenotype of dominantly inherit ed ataxia.