A National French Consensus on Gene List for the Diagnosis of Charcot–Marie–Tooth Disease and Related Disorders Using Next-Generation Sequencing
Thibaut Benquey, Emmanuelle Pion, Mireille Cossée, Martin Krahn, Tanya Stojkovic, Aurélien Perrin, Mathieu Cérino, Annamaria Molon, Anne‐Sophie Lia, Corinne Magdelaine, Bruno Francou, Anne Guiochon‐Mantel, Marie‐Claire Malinge, Éric Leguern, Nicolas Lévy, Shahram Attarian, Philippe Latour, Nathalie Bonello‐Palot
Abstract
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.