Atxn10

Homo sapiens

The autosomal dominant cerebellar ataxias (ADCAs) are a clinically and genetically heterogeneous group of disorders characterized by ataxia, dysarthria, dysmetria, and intention tremor. All ADCAs involve some degree of cerebellar dysfunction and a varying degree of signs from other components of the nervous system. A commonly accepted clinical classification (Harding, 1993 [PubMed 8421960]) divides ADCAs into 3 different groups based on the presence or absence of associated symptoms such as brain stem signs or retinopathy. The presence of pyramidal and extrapyramidal symptoms and ophthalmoplegia makes the diagnosis of ADCA I, the presence of retinopathy points to ADCA II, and the absence of associated signs to ADCA III. Genetic linkage and molecular analyses revealed that ADCAs are genetically heterogeneous even within the various subtypes. ADCA I is caused by mutations in at least 3 different genes: SCA1 (MIM 164400), which encodes ataxin-1 (ATX1; MIM 601556) and maps to 6p23; SCA2 (MIM 183090), which encodes ataxin-2 (ATX2; MIM 601517) and maps to 12q24; and SCA3, or Machado-Joseph disease (MIM 109150), which maps to 14q (MJD; MIM 607047). ADCA II is caused by mutations in SCA7 (MIM 607640). The mutations in all of these disorders involve a trinucleotide repeat expansion in the coding region of the gene. ADCA III, a predominantly cerebellar phenotype, was found in a large pedigree with linkage to chromosome 11 (SCA5; MIM 600224) and has also been found to be caused by CAG expansions in the CACNA1A gene (MIM 601011) on chromosome 19 (SCA6; MIM 183086).[supplied by OMIM]