下一代测序(NGS)被战略性地用于Charcot-Marie-Tooth病(CMT)和相关疾病的基因诊断,这些疾病被称为非综合征性遗传性外周神经病(NSIPN)。有超过100个不同的CMT相关基因参与和正在进行的发现,一个重要的实验室间多样性的基因面板存在于国家和国际层面。这里,我们介绍了法国国家罕见神经肌肉疾病网络(FILNEMUS)基因诊断部分的工作,该部分协调了使用NGS治疗周围神经病的七个法国诊断实验室。这项工作旨在建立一个独特的,基于文献证据的简单而准确的基因分类。在NSIPN中,通常分为三个亚组:(1)HMSN,遗传性运动感觉神经病,(2)dHMN,远端遗传性运动神经病,(3)HSAN,遗传性感觉自主神经病变.首先,我们报道了ClinGen的评估,第二,对于ClinGen尚未评估的基因,如果在至少两份临床出版物中报告并与一份功能证据报告相关,我们将它们归类为“确定性”,或\"limited\"否则。总的来说,我们报告了NSIPN的一个独特的共有基因列表,包括三个亚组,93个基因确定和34个有限,这是我们的基因小组分子诊断使用的好比率。
Next generation sequencing (NGS) is strategically used for genetic diagnosis in patients with Charcot-Marie-Tooth disease (CMT) and related disorders called non-syndromic inherited peripheral neuropathies (NSIPN) in this paper. With over 100 different CMT-associated genes involved and ongoing discoveries, an important interlaboratory diversity of gene panels exists at national and international levels. Here, we present the work of the French National Network for Rare Neuromuscular Diseases (FILNEMUS) genetic diagnosis section which coordinates the seven French diagnosis laboratories using NGS for peripheral neuropathies. This work aimed to establish a unique, simple and accurate gene classification based on literature evidence. In NSIPN, three subgroups were usually distinguished: (1) HMSN, Hereditary Motor Sensory Neuropathy, (2) dHMN, distal Hereditary Motor Neuropathy, and (3) HSAN, Hereditary Sensory Autonomic Neuropathy. First, we reported ClinGen evaluation, and second, for the genes not evaluated yet by ClinGen, we classified them as \"definitive\" if reported in at least two clinical publications and associated with one report of functional evidence, or \"limited\" otherwise. In total, we report a unique
consensus gene list for NSIPN including the three subgroups with 93 genes definitive and 34 limited, which is a good rate for our gene\'s panel for molecular diagnostic use.