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Estévez-Arias et al. J Transl Genet Genom 2022;6:333-52 Journal of Translational
DOI: 10.20517/jtgg.2022.04
Genetics and Genomics

Review Open Access

Genetic approaches and pathogenic pathways in the
clinical management of Charcot-Marie-Tooth disease

1,3
2,3
1,2
1,3
2
Berta Estévez-Arias , Laura Carrera-García , Andrés Nascimento , Lara Cantarero , Janet Hoenicka ,
Francesc Palau 1,3,4,5,6
1
Laboratory of Neurogenetics and Molecular Medicine - IPER, Institut de Recerca Sant Joan de Déu, Barcelona 08950, Spain.
2
Neuromuscular Unit, Department of Pediatric Neurology, Hospital Sant Joan de Déu, Barcelona 08950, Spain.
3
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona 08950, Spain.
4
Department of Genetic Medicine - IPER, Hospital Sant Joan de Déu, Barcelona 08950, Spain.
5
Clinic Institute of Medicine and Dermatology (ICMiD), Hospital Clínic, Barcelona 09036, Spain.
6
Division of Pediatrics, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona 08036, Spain.
Correspondence to: Dr. Francesc Palau, Department of Genetic and Molecular Medicine, Hospital Sant Joan de Déu, Passeig
Sant Joan de Déu, 2, Esplugues de Llobregat, Barcelona 08950, Spain. E-mail: francesc.palau@sjd.es
How to cite this article: Estévez-Arias B, Carrera-García L, Nascimento A, Cantarero L, Hoenicka J, Palau F. Genetic approaches
and pathogenic pathways in the clinical management of Charcot-Marie-Tooth disease. J Transl Genet Genom 2022;6:333-52.
https://dx.doi.org/10.20517/jtgg.2022.04
Received: 19 Jan 2022 First Decision: 24 Apr 2022 Revised: 18 May 2022 Accepted: 9 Jun 2022 Published: 1 Aug 2022
Academic Editors: Andrea L. Gropman, C. Alexander Valencia Copy Editor: Fangling Lan Production Editor: Fangling Lan

Abstract
Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder, affecting at least 1 in
2500 individuals. CMT refers to a heterogeneous group of inherited neuropathies from both phenotypic and
genetic points of view. Over the last decades, there have been important advances not only in the identification of
causative genes but also in understanding the molecular basis for many forms of CMT. In fact, to date, around 100
genes have been related to CMT disease, thanks to next generation sequencing techniques, and they have been
proven to affect either the myelin or axon of peripheral nerves. Moreover, its genetic diagnosis has remarkedly
improved, although there are still difficulties when it comes to treatment. In this review, we explore in depth the
eight most prevalent genes associated with CMT: GDAP1, GJB1, HINT1, MFN2, MPZ, PMP22, SH3TC2, and SORD. We
also address the disrupted cellular processes and pathophysiological mechanisms involved in the disease. A better
understanding of the pathogenic mechanisms responsible for each type of CMT would be essential to identifying
molecular targets and therapeutic strategies.

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

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