High phenotypic diversity in patients with CMT linked to a mutation in the MPZ gene?

Hereditary sensory-motor neuropathies type Charcot-Marie-Tooth (or CMT) are clinically and genetically heterogeneous pathologies. Quite common in the general population, they result in a motor deficit of varying severity and scalability in the extremities of the limbs, associated with sensory disorders rarely in the foreground. Almost 110 genes, inherited on autosomal dominant or recessive or X-linked dominant mode, are responsible, whether they are demyelinating forms (CMT1) or axonal forms (CMT2). 

In an article published in June 2021, a group of neurologists belonging to eleven French neuromuscular reference centres dealing with this type of patient reported a census of patients carrying mutations in the MPZ gene encoding the myelin protein Po. This study was designed prospectively as part of a possible therapeutic trial based on sephine, a product that acts on misfolded proteins. In this study, 91 patients carrying pathogenic variants of MPZ and belonging to 61 distinct families were identified. The study shows a very large phenotypic diversity, the same mutation can cause both an axonal CMT and a demyelinating CMT. Three age groups were formed, the first (less than 22 years old) and the second (23 to 47 years old) being correlated with a progressive deterioration of a functional CMT score. The authors conclude that future trials should target these subpopulations as a priority.


Genotype-phenotype correlation in French patients with myelin protein zero gene-related inherited neuropathy. Subréville M, Bonello-Palot N, Yahiaoui D, Beloribi-Djefaflia S, Fernandes S, Stojkovic T, Cassereau J, Péréon Y, Echaniz-Laguna A, Violleau MH, Soulages A, Louis SL, Masingue M, Magot A, Delmont E, Sacconi S, Adams D, Labeyrie C, Genestet S, Noury JB, Chanson JB, Lévy N, Juntas-Morales R, Tard C, Sole G, Attarian S. Eur J Neurol. 2021 (Juin).