Chromosomal assignment of the second locus for autosomal dominant cerebellar ataxia (SCA2) to chromosome 12q23-24.1.

The autosomal dominant cerebellar ataxias (ADCA) are a group of neurodegenerative disorders characterized by onset with gait ataxia, dysarthria, dysmetria and dysdiadochokinesia. We have demonstrated previously genetic heterogeneity within these disorders by excluding the disease locus from the documented spinocerebellar ataxia locus (SCA1) on chromosome 6p in a large Cuban founder population. We now report the assignment of a second locus for ADCA (SCA2) to chromosome 12q23-24.1 following linkage analyses carried out for the Cuban pedigrees, with probable flanking markers D12S58 and phospholipase A2. Investigation of linkage to the interval containing SCA2 for seven French ADCA families, previously excluded from linkage to SCA1, provides preliminary data suggesting the existence of a third ADCA locus (SCA3).

Search for the chromosomal location of autosomal dominant cerebellar ataxia from Holguin, Cuba: exclusion from candidate regions on chromosome 4 and 11q.

A gene locus for autosomal dominant cerebellar ataxia (ADCA) has been found on chromosome 6p and named spinocerebellar ataxia 1. However, linkage exclusion from chromosome 6p and thus locus heterogeneity has been proven in Cuban ADCA, the largest known collective of ADCA patients, probably due to a founder effect. Two chromosomal regions were analyzed for linkage to Cuban ADCA: chromosome 4, since a pericentromeric inversion has been reported in a member of a European ADCA family, and chromosome 11q22-23, since it is known to contain the gene locus for ataxia telangiectasia, the main autosomal recessive disorder of cerebellar degeneration. In neither region was evidence for linkage found.