COMPARATIVE STUDY
JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
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Spinocerebellar ataxia type 26 maps to chromosome 19p13.3 adjacent to SCA6.

The dominantly inherited spinocerebellar ataxias (SCA) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by progressive gait ataxia, upper limb incoordination, and dysarthria. We studied a six-generation kindred of Norwegian ancestry with pure cerebellar ataxia inherited in an autosomal dominant pattern. All affected family members had a slowly progressive cerebellar ataxia, with an age of onset range from 26 to 60 years. Brain magnetic resonance imaging study of 11 affected patients showed that atrophy was confined to the cerebellum. After excluding all the known SCAs using linkage analysis or direct mutation screen, we conducted a genomewide genetic linkage scan. With the aid of a novel linkage analysis strategy, we found linkage between the disease locus and marker D19S591 and D19S1034. Subsequent genetic and clinical analysis identified a critical region of 15.55cM interval on chromosome 19p13.3, flanked by markers D19S886 and D19S894, and have established a new genetic locus designated SCA26. The SCA26 locus is adjacent to the genes for Cayman ataxia and SCA6. The region consists of 3.3 million base pairs (Mb) of DNA sequences with approximately 100 known and predicted genes. Identification of the responsible gene for SCA26 ataxia will provide further insight into mechanisms of neurodegeneration.

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