振戦を伴なう常染色体優性遺伝性脊髄小脳変性症の連鎖解析

概要

論文の詳細を見る
Autosomal dominant cerebellar ataxias (ADCAs) are genetically heterogeneous neurodegenerative disorders. To date, 10 causative genes and at least 10 loci for spinocerebellar ataxias (SCAs) have been identified. The causative genes for at least 20% of ADCAs, however, still remain to be elucidated. We identified two Japanese families with unique clinical presentations. The mean ages at onset were 37.5 years (27〜47) in family A and 22.3 years (12〜35) in family B. The affected members showed cerebellar ataxia, postural and action tremor of the trunk and upper extremities and a very slow progression rate, remaining ambulatory without support for one or two decades after the onset. Brain MRI revealed cerebellar atrophy without brain stem atrophy. The possibility of the previously reported SCAs was excluded by mutational analyses and linkage analyses. A genome-wide linkage analysis confirmed linkage to chromosome 3p26.1-25.3, with the highest cumulative two-point (Z=3.02) and multipoint (Z=3.30) lod scores at D3S3728. The flanking markers D3S1620 and D3S3691 define a candidate region of an interval of 14.7cM that partly overlaps with the recently identified locus of SCA15. Identification of the causative gene (s) is required to conclusively determine whether the causative gene is allelic to or distinct from that of SCA15.
2003-10-10