Linkage between late onset,dominant spinocerebellar ataxia and HLA

Summary Three families with at least three generations of family members affected with spino-cerebellar ataxia transmitted in a dominant fashion were studied. In each family every available member, above the lowest age at onset observed in that family, was subject to a thorough clinical investigation and blood was sampled for HLA,A,B and C-typing. In all three families the affected members had signs which were characteristic for cerebellar ataxia, without spasticity or dementia. In two families the mean age at onset was in accordance with the literature, viz. in the fourth and fifth decade, while in the third family mean age at onset was over 50 years. In the two pedigrees with the usual age at onset there was evidence of linkage between the disease and the HLA-system with a combined lod score of 1.499 at a recombination fraction of 0.05 for males. The third pedigree gave negative lod scores for linkage between HLA and the disease locus for both males and females but in this family also the high age at onset was indicative of genetic heterogeneity.