Clinical and genetic investigation in Chinese patients with demyelinating Charcot-Marie-Tooth disease
Clinical and genetic investigation in Chinese patients with demyelinating Charcot-Marie-Tooth disease
复制标题
中国脱髓鞘夏科-马里-图思病患者的临床和遗传学调查
DOI：
10.1111/jns.12277
复制
发表时间：
2018-12-01
影响因子：
3.8
通讯作者：
Wang, Ning
中科院分区：
文献类型：
--
作者：
He, Jin;Guo, Lingling;Wang, Ning
脱髓鞘Charcot-Marie-Tooth病(CMT)是CMT最常见的亚型。它主要由17p11.2杂合复制引起，但也由影响雪旺细胞发育和功能的20多个基因突变引起。为了解中国人脱髓鞘CMT患者的基因突变谱和临床特征，我们收集了44例脱髓鞘CMT患者的队列，并采用多重连接依赖的探针扩增(MLPA)和靶向下一代测序(NGS)技术进行了筛查。MLPA检测显示77.3%的脱髓鞘CMT患者携带17p11.2杂合性重复序列，6.8%的患者携带MPZ基因第6外显子的杂合性缺失，进一步证实了MPZ基因存在新的c.674_675insA突变。在17p12杂合性重复的患者中，3组独立的家系在同一家系内的CMT表型不一致。靶向NGS技术显示，发现了6个候选突变，其中包括1个先前报道的突变(GDAP1：C.571C>；T)和5个新突变(SBF2：c.415T>；C，c.619G>；T，c.1258A>；G；GDAP1：c.589delC；PMP22：c.318delT)。结论：MLPA技术结合靶向NGS可提高脱髓鞘CMT的基因诊断成功率。
Demyelinating Charcot-Marie-Tooth disease (CMT) is the most common subtype of CMT. It is caused mainly by 17p11.2 heterozygous duplication, but also by mutations in more than 20 genes which affect development and function of Schwann cells. To investigate the profile of genes mutated and clinical features in demyelinating CMT of Chinese descent, we collected a cohort of 44 demyelinating CMT patients and screened them using multiplex ligation-dependent probe amplification (MLPA) and targeted next-generation sequencing (NGS) technology. The MLPA technology revealed that 77.3% demyelinating CMT patients harbored 17p11.2 heterozygous duplication and 6.8% patients harbored heterozygous deletion of exon 6 of MPZ gene, that was further confirmed a novel c.674_675insA mutation in MPZ gene. In the patients with 17p12 heterozygous duplication, 3 sets of independent families were discordant for the CMT phenotype within the same family. The targeted NGS technology revealed that 6 candidate mutations including 1 previously reported mutation (GDAP1: c.571C>T) and 5 novel mutations (SBF2: c.415T>C, c.619G>T, c.1258A>G; GDAP1: c.589delC; PMP22: c.318delT) were found. In conclusion, combined MLPA technique with targeted NGS, the demyelinating CMT genetic diagnostic success rate was increased.