Molecular epidemiology and clinical spectrum of hereditary spastic paraplegia in the Japanese population based on comprehensive mutational analyses
Molecular epidemiology and clinical spectrum of hereditary spastic paraplegia in the Japanese population based on comprehensive mutational analyses
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DOI：
10.1038/jhg.2013.139
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发表时间：
2014-03-01
影响因子：
3.5
通讯作者：
Tsuji, Shoji
中科院分区：
文献类型：
--
作者：
Ishiura, Hiroyuki;Takahashi, Yuji;Tsuji, Shoji
遗传性痉挛性截瘫（HSP）是一种遗传异质性最强的神经退行性疾病，以下肢进行性痉挛和锥体束无力为特征。由于430个致病基因已被确定，筛选多个基因是必要的，以建立个体患者的HSP分子诊断。为了阐明日本人群中HSP的分子流行病学，我们使用重测序微阵列、基于阵列的比较基因组杂交和桑格测序对HSP的16个致病基因（L1 CAM、PLP 1、ATL 1、SPAST、CYP 7 B1、NIPA 1、SPG 7、KIAA 0196、KIF 5A、HSPD 1、BSCL 2、SPG 11、SPG 20、SPG 21、REEP 1和ZFYVE 27）进行了突变分析。对129名日本患者的突变分析显示，46名患者发生了49种突变，其中32种是新的。67.3%（33/49）的HSP患者获得了分子诊断。即使在散发性HSP患者中，也有11.1%（7/63）的患者发现了突变。本研究阐明了HSP在日本人群中的分子流行病学，并进一步拓宽了HSP的突变谱和临床谱。
Hereditary spastic paraplegia (HSP) is one of the most genetically heterogeneous neurodegenerative disorders characterized by progressive spasticity and pyramidal weakness of lower limbs. Because 430 causative genes have been identified, screening of multiple genes is required for establishing molecular diagnosis of individual patients with HSP. To elucidate molecular epidemiology of HSP in the Japanese population, we have conducted mutational analyses of 16 causative genes of HSP (L1CAM, PLP1, ATL1, SPAST, CYP7B1, NIPA1, SPG7, KIAA0196, KIF5A, HSPD1, BSCL2, SPG11, SPG20, SPG21, REEP1 and ZFYVE27) using resequencing microarrays, array-based comparative genomic hybridization and Sanger sequencing. The mutational analysis of 129 Japanese patients revealed 49 mutations in 46 patients, 32 of which were novel. Molecular diagnosis was accomplished for 67.3% (33/49) of autosomal dominant HSP patients. Even among sporadic HSP patients, mutations were identified in 11.1% (7/63) of them. The present study elucidated the molecular epidemiology of HSP in the Japanese population and further broadened the mutational and clinical spectra of HSP.