A novel autosomal dominant spinocerebellar ataxia (SCA16) linked to chromosome 8q22.1-24.1

Objective: To characterize a distinct form of autosomal. dominant cerebella r ataxia (ADCA) clinically and genetically. Background : ADCAs are a clinic ally,. pathologically, and genetically heterogeneous group of neurodegenera tive disorders. Nine responsible genes have been identified for SCA-1, -2, -3, -6, -7, -8, -10, and -12 and dentatorubral-pallidoluysian. atrophy (DRP LA) Loci for SCA-4, -5, -11, -13, and -14 have been mapped. Methods: The au thors studied a four-generation Japanese family with ADCA. The 19 members w ere enrolled in this study. The authors performed the mutation analysis by PCR and a genome-wide Linkage analysis. Results: Nine members (five men and four women) were affected. The ages at onset ranged fi om 20 to 66 years. All affected members showed pure cerebellar ataxia, and three patients also had head tremor. Head MRI demonstrated cerebellar atrophy without brain st em involvement. The mutation analysis by PCR excluded diagnoses of SCA-1, - 2, -3, -6, -7, -8, and -12 and DRPLA. The linkage analysis suggested linkag e to a locus on chromosome 8q22.1-24.1, with the highest two-point, lod sco re at D8S1804 (Z = 3.06 at theta = 0.0). The flanking markers D8S270 and D8 S1720 defined a candidate region of an approximately 37.6-cM interval. This candidate region was different from the loci for SCA-4, -5, -10, -11, -13, and -14. Conclusion: The family studied had a genetically novel type of SC A (SCA-16).