A National French Consensus on Gene List for the Diagnosis of Charcot–Marie–Tooth Disease and Related Disorders Using Next-Generation Sequencing

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.

Identification of transcriptional regulators using a combined disease module identification and prize-collecting Steiner tree approach

“…Nevertheless, the current study has several limitations. The outputs of network-based methods are influenced by the quality of the backbone networks [82], emphasizing that careful selection of backbone networks or filtering for high-confidence edges is important when performing network-based analysis. However, as more molecular data are generated, including tissue- and cell type-specific data, we expect the increasing reliability of template molecular networks and higher confidence annotation scores of TF-target associations across different biological contexts and the greater applicability for network-based tools.…”

Caractéristiques cliniques et électrophysiologiques des femmes atteintes de la maladie de Charcot-Marie-Tooth liée à l’X

“…Parmi ceux-ci, on distingue les CMT1 Les gènes responsables des CMT peuvent être impliqués dans divers processus biologiques, tels que la synthèse ou la dégradation de la myéline, la synthèse protéique, le transport interne à la cellule, la régulation du fonctionnement mitochondrial, ou encore les facteurs de transcription impliqués dans la régulation de gène de la myéline. Il reste encore cependant de nombreux gènes, 34 selon Benquey T. et al (11), pour lesquels nous ne connaissons pas le processus impliqué.…”

SORD‐related peripheral neuropathy in a French and Swiss cohort: Clinical features, genetic analyses, and sorbitol dosages

“…Charcot-Marie-Tooth disease (CMT) and distal hereditary motor neuropathy (dHMN) are the most common types of hereditary peripheral neuropathies [1]. CMT is responsible for motor and sensory disabilities, usually affecting children and young adults.…”

“…Inheritance is either autosomal recessive, dominant, or X-linked [4]. Common causative genes responsible for both dHMN and CMT2 such as HSPB1, IHGMBP2, and GARS1 have been described and therefore a phenotype overlap can be observed between these two forms of peripheral neuropathies [1,5].…”