Koh Kishin, Ishiura Hiroyuki, Tsuji Shoji, Takiyama Yoshihisa
Department of Neurology, Graduate School of Medical Sciences, University of Yamanashi, 409-3898 Yamanashi, Japan.
Department of Neurology, Graduate School of Medicine, The University of Tokyo, 113-8655 Tokyo, Japan.
Brain Sci. 2018 Aug 13;8(8):153. doi: 10.3390/brainsci8080153.
Hereditary spastic paraplegias (HSPs) are a group of neurodegenerative disorders characterized by weakness and spasticity of the lower extremities. HSPs are heterogeneous disorders that involve over 80 causative genes. The frequency of HSPs is estimated to be 10⁻100/1,000,000. With this background, the Japanese research group "Japan Spastic Paraplegia Research Consortium: JASPAC" was organized in 2006 to elucidate the molecular epidemiologies of HSPs in Japan and the molecular pathologies of HSPs. To date, the JASPAC has collected 714 HSP families and analyzed 488 index patients. We found 279 pathogenic variants or probable pathogenic variants of causative genes in the 488 HSP patients. According to our results, we found 178 families with autosomal dominant patients (65%), and 101 with autosomal recessive and sporadic patients (48%). We found 119 patients with SPG4, 17 with SPG3A, 15 with SPG31, 13 with SPG11, and 11 with SPG10. Other HSP genes were the cause in less than five patients. On the other hand, we could not find causative genes in 35% of the autosomal dominant patients, or 52% of the autosomal recessive and sporadic patients. We are now trying to find new causative genes and elucidate the molecular mechanisms underlying HSPs.
遗传性痉挛性截瘫（HSPs）是一组以双下肢无力和痉挛为特征的神经退行性疾病。HSPs是异质性疾病，涉及80多个致病基因。据估计，HSPs的发病率为10⁻100/1,000,000。在此背景下，日本研究团队“日本痉挛性截瘫研究联盟：JASPAC”于2006年成立，旨在阐明日本HSPs的分子流行病学以及HSPs的分子病理学。迄今为止，JASPAC已收集了714个HSP家系，并对488名索引患者进行了分析。我们在488名HSP患者中发现了279个致病基因的致病性变异或可能的致病性变异。根据我们的结果，我们发现178个家系为常染色体显性遗传患者（65%），101个家系为常染色体隐性遗传和散发性患者（48%）。我们发现119名患者携带SPG4基因，17名携带SPG3A基因，15名携带SPG31基因，13名携带SPG11基因，11名携带SPG10基因。其他HSP基因导致的患者少于5名。另一方面，我们在35%的常染色体显性遗传患者或52%的常染色体隐性遗传和散发性患者中未发现致病基因。我们目前正在努力寻找新的致病基因，并阐明HSPs的分子机制。
