Mapping of a new autosomal dominant spinocerebellar ataxia to chromosome 22.
The autosomal dominant cerebellar ataxias (ADCAs) are a clinically and genetically heterogeneous group of disorders. The clinical symptoms include cerebellar dysfunction and associated signs from dysfunction in other parts of the nervous system. So far, five spinocerebellar ataxia (SCA) genes have been identified: SCA1, SCA2, SCA3, SCA6, and SCA7. Loci for SCA4 and SCA5 have been mapped. However, approximately one-third of SCAs have remained unassigned. We have identified a Mexican American pedigree that segregates a new form of ataxia clinically characterized by gait and limb ataxia, dysarthria, and nystagmus. Two individuals have seizures. After excluding all known genetic loci for linkage, we performed a genomewide search and identified linkage to a 15-cM region on chromosome 22q13. A maximum LOD score of 4.3 (recombination fraction 0) was obtained for D22S928 and D22S1161. This distinct form of ataxia has been designated "SCA10." Anticipation was observed in the available parent-child pairs, suggesting that trinucleotide-repeat expansion may be the mutagenic mechanism.
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Division of Neurology and Rose Moss Laboratory for Parkinson's and Neurodegenerative Diseases, Burns and Allen Research Institute, Cedars-Sinai Medical Center, University of California, Los Angeles, CA 90048, USA.
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Grewal
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Pulst
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D000293:Adolescent; D000328:Adult; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22; D005260:Female; D005799:Genes, Dominant; D006239:Haplotypes; D006801:Humans; D008297:Male; D010375:Pedigree; D013132:Spinocerebellar Degenerations / Q000235:genetics* / Q000503:physiopathology