Clinical and Molecular Characterization of BSCL2 Mutations in a Taiwanese Cohort with Hereditary Neuropathy.
Clinical and Molecular Characterization of BSCL2 Mutations in a Taiwanese Cohort with Hereditary Neuropathy.
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DOI：
10.1371/journal.pone.0147677
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Lee YC
中科院分区：
文献类型：
--
作者：
Hsiao CT;Tsai PC;Lin CC;Liu YT;Huang YH;Liao YC;Huang HW;Lin KP;Soong BW;Lee YC
一小群遗传性神经病患者，已被证明是由BSCL 2基因突变引起的。然而，在台湾，关于BSCL 2突变在遗传性神经病中的作用的信息很少。利用靶向测序，76例分子未分配的腓骨肌萎缩症2型（CMT2）和8例远端遗传性运动神经病（dHMN），从348例无关的遗传性神经病患者中选择，筛选BSCL 2编码区的突变。发现了两个杂合BSCL 2突变，p.S90L和p.R96H，其中p.R96H突变是新的。P.S90L在CMT2家系中鉴定，而P.R96H在明显散发的dHMN患者中鉴定。体外研究表明，p.R96H突变导致显著低的seipin表达和降低的细胞活力。在台湾，BSCL 2突变占少数遗传性神经病患者的比例。p.R96H突变与dHMN相关。这项研究扩大了BSCL 2突变的分子谱，也强调了BSCL 2突变在分子未分配的遗传性神经病中的致病作用。
A small group of patients with inherited neuropathy that has been shown to be caused by mutations in the BSCL2 gene. However, little information is available about the role of BSCL2 mutations in inherited neuropathies in Taiwan. Utilizing targeted sequencing, 76 patients with molecularly unassigned Charcot-Marie-Tooth disease type 2 (CMT2) and 8 with distal hereditary motor neuropathy (dHMN), who were selected from 348 unrelated patients with inherited neuropathies, were screened for mutations in the coding regions of BSCL2. Two heterozygous BSCL2 mutations, p.S90L and p.R96H, were identified, of which the p.R96H mutation is novel. The p.S90L was identified in a pedigree with CMT2 while the p.R96H was identified in a patient with apparently sporadic dHMN. In vitro studies demonstrated that the p.R96H mutation results in a remarkably low seipin expression and reduced cell viability. BSCL2 mutations account for a small number of patients with inherited neuropathies in Taiwan. The p.R96H mutation is associated with dHMN. This study expands the molecular spectrum of BSCL2 mutations and also emphasizes the pathogenic role of BSCL2 mutations in molecularly unassigned hereditary neuropathies.