This study aimed to describe the clinical, genetic, and epidemiological features of Charcot-Marie-Tooth disease (CMT) in Brazilian patients from a tertiary center, and to compare our data with previously published findings. This retrospective observational study conducted between February 2015 and July 2020 evaluated 503 patients (94 families and 192 unrelated individuals), diagnosed with CMT. Clinical and neurophysiological data were obtained from electronic medical records and blood samples were used for genetic analyses. Multiplex ligation-dependent probe amplification was used to assess duplications/deletions in PMP22. Sanger sequencing of GJB1 was performed in cases of suspected demyelinating CMT. Targeted gene panel sequencing was used for the remaining negative demyelinating cases and all axonal CMT cases. The first decade of life was the most common period of disease onset. In all, 353 patients had demyelinating CMT, 39 had intermediate CMT, and 111 had axonal CMT. Pathogenic or likely pathogenic variants were identified in 197 index cases. The most common causative genes among probands were PMP22 (duplication) (n = 116, 58.88%), GJB1 (n = 23, 11.67%), MFN2 (n = 12, 6.09%), GDAP1 (n = 7, 3.55%), MPZ (n = 6, 3.05%), PMP22 (point mutation) (n = 6, 3.05%), NEFL (n = 3, 1.52%), SBF2 (n = 3, 1.52%), and SH3TC2 (n = 3, 1.52%). Other identified variants were ≤1% of index cases. This study provides further data on the frequency of CMT subtypes in a Brazilian clinical-based population and highlights the importance of rarer and previously undiagnosed variants in clinical practice.

中文翻译：

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Charcot-Marie-Tooth 病：来自巴西大型神经肌肉参考中心的患者遗传特征

本研究旨在描述来自一家三级中心的巴西患者的 Charcot-Marie-Tooth 病 (CMT) 的临床、遗传和流行病学特征，并将我们的数据与之前发表的研究结果进行比较。这项在 2015 年 2 月至 2020 年 7 月期间进行的回顾性观察研究评估了 503 名诊断为 CMT 的患者（94 个家庭和 192 名无关个体）。从电子病历中获得临床和神经生理学数据，并将血液样本用于遗传分析。多重连接依赖性探针扩增用于评估PMP22中的重复/缺失。GJB1的Sanger测序在疑似脱髓鞘 CMT 的情况下进行。靶向基因组测序用于剩余的阴性脱髓鞘病例和所有轴突 CMT 病例。生命的头十年是疾病发作最常见的时期。总共有 353 名患者患有脱髓鞘性 CMT，39 名患有中间型 CMT，111 名患有轴突型 CMT。在 197 个指示病例中发现了致病性或可能的致病性变异。先证者中最常见的致病基因是PMP22 (重复) (n = 116, 58.88%)、GJB1 (n = 23, 11.67%)、MFN2 (n = 12, 6.09%)、GDAP1 (n = 7, 3.55%) , MPZ (n = 6, 3.05%), PMP22 (点突变) (n = 6, 3.05%), NEFL (n = 3, 1.52%), SBF2(n = 3, 1.52%) 和SH3TC2 (n = 3, 1.52%)。其他已确定的变体占索引病例的 ≤1%。这项研究提供了有关巴西临床人群中 CMT 亚型频率的进一步数据，并强调了临床实践中罕见和以前未诊断的变异的重要性。