Autosomal dominant cerebellar ataxia type I linked to chromosome 12q (SCA2: spinocerebellar ataxia type 2)

Spinocerebellar ataxia 2 (SCA2) is one of the loci for the clinically and genetically heterogeneous group of autosomal dominant type I cerebellar ataxias. After initial linkage to chromosome 12q in Cuban families, SCA2 was shown to be the gene responsible for the disease in Italian, Tunisian, French-Canadian, Austrian-Canadian and Martinican kindreds with dominant ataxia, and the candidate interval was reduced to 6.4 cM between markers D12S84 and D12S79. Comparison of patients from families of different geographical origins clearly demonstrates the clinical interfamilial variability of the clinical signs which reaches statistical significance for the frequency of extrapyramidal rigidity, postural tremor and dementia. The most striking difference between the 29 Martinican SCA2 patients and those with SCA1 on chromosome 6p or SCA3/MJD on chromosome 14q is the greater frequency of hyporeflexia in the former. A mean 12.5 year anticipation is observed, with a more rapid clinical course of the disease in successive generations, indicating that an expanded trinucleotide repeat probably constitutes the underlying molecular mechanism.