| Research Abstract |
1) Hereditary spastic paraplegia (SPG) is a cluster of genetically heterogeneous disorders. At now, 13 SPG loci have been determined. Of them, SPG4 locates on chromosome 2p2l-p22, and mutation of spastin gene is known to cause the disorder. We previously identified a first Japanese family with SPG4, by linkage analysis. SPG4 is estimated to be a major disorder in a cluster of hereditary SPG.Since its frequency in Japanese has not been known, we studied mutation of spastin gene in the probands from 12 unrelated families with hereditary SPG.All exons of spastin gene in each individual were analyzed with direct sequencing method after PCR amplification. Consequently, 5 of 12 families carried different mutations in spastin gene : 3 missense mutations (R499C, Q347K, K388R) and 2 splice site mutations (l370+1g→t, 1742-1g→t). Our results disclosed that a part of SPG in Japanese is caused by spastin gene mutation, frequency of SPG4 in the SPG of Japanese is estimated to be 40%, and those different mutations imply unrelated founders in each family with SPG4.
2) In spinocerebellar ataxias, neither responsible genes nor mutations are known in approximately 40 % hereditary cortical cerebellar atrophy (CCA). We performed systematic linkage study in a 3-generation family with dominant CCA, and successfully determined new SCA locus to chromosome l9ql3. This novel locus is now registered as SCA14 on human gene map.
3) We studied frequency of SPG in Hokkaido. In 288 patients with hereditary ataxia, 5.7 % were pure form and 4.8% were complicated form of SPG.
4) Throughout study of complicated SPG, we reported a SPG characterized by 1) dominant leukoencephalopathy associated with cerebellar ataxia, and another SPG characterized by 2) recessive inheritance, congenital cataract, ataxia, callosal atrophy, and axonal neuropathy.
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