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.

Charcot-Marie-Tooth (CMT) 病代表了一个独特的遗传性周围神经病变亚组，在世界范围内具有显着的患病率，并表现出表型和遗传异质性。电生理学研究将 CMT 主要分为脱髓鞘型或轴突型。在这项研究中，我们调查了 2019 年 1 月至 2021 年 12 月 34 名有症状的脱髓鞘 CMT 个体中的 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，我们应用了一种合理的算法：最初分析了PMP22基因对于重复，如果PMP22 -重复测试为阴性，则其他最致病基因（GJB1，MPZ）和PMP22然后进行测序，如果在上述测试中未检测到变异，则最终进行全外显子组测序（WES）测试。共有 17 名患者（≅ 74%；n  = 23）被发现在脱髓鞘 CMT 相关基因中存在致病变异，在这些变异中，PMP22重复是最常见的（≅ 41%）。CMT1、CMTX 和 CMT4 亚型分别在 10、5 和 2 个个体中表现出来。GJB1和SBF2基因是除 CMT1 之外唯一检测到的与 CMT 相关的基因。我们还报告了总共五个新变体：GJB1 中的 c.379A > C (p.Ile127Leu) 和 c.548G > T (p.Arg183Leu) 变体，NEFL中的 c.988G > T (p.Glu330Ter) 变体, c.765_770delCCCTAT (p.Pro256_Ile257del) 和 c.2552A > C (p.His851Pro) SBF2 中的变体。随着对 CMT 的病理生理学和分子机制的理解不断快速发展，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修饰疗法，将很快在临床环境中实施。