Graduate Program in Medicine, Medical Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Translational Neurogenetics Laboratory, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
Clin Genet. 2020 Aug;98(2):185-190. doi: 10.1111/cge.13793. Epub 2020 Jun 29.
Diagnostic yield of genetic studies for Charcot-Marie-Tooth disease (CMT) is little known, with a lack of epidemiological data to build better diagnostic strategies outside the United States and Europe. We aimed to evaluate the performance of two molecular diagnostic strategies for patients with CMT, and to characterize epidemiological findings of these conditions in southern Brazil. We performed a single-center cross-sectional study, in which 94 patients (55 families) with CMT suspicion were evaluated. Overall, the diagnostic yield of the combined strategy of Multiplex-ligation-dependent-probe-amplification (MLPA) of PMP22/GJB1/MPZ and GJB1/MPZ/PMP22 Sanger sequencing was 63.6% (28/44) for index cases with demyelinating/intermediate CMT suspicion (21 CMT1A-PMP22, 5 CMTX1-GJB1 and 2 with probably CMT1B-MPZ diagnosis). Five of the 11 index cases (45.4%) with axonal CMT had at least a possible diagnosis with next generation sequencing (NGS) panel of 104 inherited neuropathies-related genes (one each with CMT1A-PMP22, CMT2A-MFN2, CMT2K-GDAP1, CMT2U-MARS, CMT2W-HARS1). Detailed clinical, neurophysiological and molecular data of families are provided. Sequential molecular diagnosis strategies with MLPA plus target Sanger sequencing for demyelinating/intermediate CMT had high diagnostic yield, and almost half of axonal CMT families had at least a possible diagnosis with the comprehensive NGS panel. Most frequent subtypes of CMT in our region are CMT1A-PMP22 and CMTX1-GJB1.
Charcot-Marie-Tooth 病（CMT）的基因研究诊断率知之甚少，由于缺乏美国和欧洲以外的更好的诊断策略的流行病学数据。我们旨在评估两种分子诊断策略对 CMT 患者的性能，并描述巴西南部这些疾病的流行病学发现。我们进行了一项单中心横断面研究，其中评估了 94 名（55 个家庭）CMT 可疑患者。总体而言，对于脱髓鞘/中间 CMT 怀疑指数病例，多重连接依赖性探针扩增（MLPA）的 PMP22/GJB1/MPZ 和 GJB1/MPZ/PMP22 Sanger 测序的联合策略的诊断率为 63.6%（28/44）（21 例 CMT1A-PMP22，5 例 CMTX1-GJB1 和 2 例可能 CMT1B-MPZ 诊断）。11 例轴索 CMT 指数病例中有 5 例（45.4%）至少通过 104 种遗传性神经病变相关基因的下一代测序（NGS）面板（分别为 1 例 CMT1A-PMP22、CMT2A-MFN2、CMT2K-GDAP1、CMT2U-MARS、CMT2W-HARS1）有一个可能的诊断。提供了详细的家族临床，神经生理学和分子数据。脱髓鞘/中间 CMT 的 MLPA 加靶向 Sanger 测序的顺序分子诊断策略具有较高的诊断率，几乎一半的轴索 CMT 家族至少可以通过综合 NGS 面板进行诊断。我们地区最常见的 CMT 亚型是 CMT1A-PMP22 和 CMTX1-GJB1。
