Charcot-Marie-Tooth(CMT)疾病代表了遗传性周围神经病的一个独特亚组,在全世界范围内患病率很高,并且表现出表型和遗传异质性。电生理研究将CMT亚分类为脱髓鞘或轴突类型。在这项研究中,我们调查了2019年1月至2021年12月34例有症状的脱髓鞘CMT患者中23名先证者的土耳其队列的分子特征.为了确定潜在的遗传原因,我们应用了一个合理的算法:PMP22基因最初被分析重复,如果PMP22重复测试是阴性的,然后对其他大多数致病基因(GJB1,MPZ)和PMP22进行测序,如果在上述测试中没有检测到变异,最终进行了全外显子组测序(WES)试验.共发现17例患者(约74%;n=23)在脱髓鞘CMT相关基因和变异中具有致病变异,PMP22重复是最常见的(41%)。CMT1,CMTX,CMT4亚型表现为10种,五,和两个人分别。除了CMT1,GJB1和SBF2基因是唯一检测到的与CMTs相关的基因。我们还报道了总共五个新的变体:c.379A>C(p。Ile127Leu)和c.548G>T(p。GJB1中的Arg183Leu)变体,c.988G>T(p。Glu330Ter)在NEFL中的变体,c.765_770delCCCTAT(p。Pro256_Ile257del)和c.2552A>C(p。SBF2中的His851Pro)变体。随着对CMT病理生理学和分子机制的认识不断发展,许多治疗策略选择,包括有前途的小分子化合物,基因替代疗法,或疾病改善疗法将很快在临床上实施。
Charcot-Marie-Tooth (CMT) disease represents a distinct subgroup of inherited peripheral neuropathies with a significant prevalence throughout the world and manifests both phenotypic and genetic heterogeneity. Electrophysiological studies subclassify CMT mainly as demyelinating or axonal types. In this study, we investigated the molecular characteristics of a Turkish cohort of 23 probands out of 34 symptomatic demyelinating CMT individuals from January 2019 to December 2021. In order to identify the underlying genetic cause, we applied a rational algorithm: PMP22 gene was initially analyzed for duplication, if PMP22-duplication testing was negative, other most causative genes (GJB1, MPZ) and PMP22 were then sequenced and if no variant was detected at aforementioned tests, whole exome sequencing (WES) test was finally performed. A total of 17 patients (≅ 74%; n = 23) were found to harbor a disease-causing variant in demyelinating CMT-related genes and among the variants, PMP22-duplication was the most frequent (≅ 41%). CMT1, CMTX, and CMT4 subtypes were manifested in ten, five, and two individuals respectively. GJB1 and SBF2 genes were the only detected genes associated with the CMTs other than CMT1. We also reported totally five novel variants: c.379A > C (p.Ile127Leu) and c.548G > T (p.Arg183Leu) variants in GJB1, c.988G > T (p.Glu330Ter) variant in NEFL, c.765_770delCCCTAT (p.Pro256_Ile257del) and c.2552A > C (p.His851Pro) variants in SBF2. As the understanding of pathophysiology and molecular mechanisms of CMT continues to evolve rapidly, many therapeutic strategy options including promising small-molecular compounds, gene replacement therapy, or disease-modifying therapies will soon be implemented in the clinical setting.