Two new genes in Charcot-Marie-Tooth disease

• The gene for a seventh aminoacyl-tRNA synthetase has just been implicated in axonal dominantEn génétique, c’est la caractéristique d’un individu qui n’a besoin que d’un seul exemplaire d’un certain gène (allèle) pour s’exprimer. Cet exemplaire unique peut venir du père ou de la mère. Charcot-Marie-Tooth disease (CMT) thanks to whole exome sequencing of three unrelated individuals: this is asparaginyl-tRNA synthetase (NARS1); the functional study showed that it is a loss-of-function mutationModification soudaine et transmissible du matériel génétique. Elle peut être spontanée ou induite par des agents dits » mutagènes » (radiations, produits toxiques,…)..
• A homozygous variant affecting the splice site of the NDUFS6 gene, which encodes a subunit of complex I of the mitochondrial respiratory chain, and already known to cause fatal Leigh syndrome, was found to be involved in five patients from three families with axonal Charcot-Marie-Tooth disease associated with nystagmus; unlike those found in fatal forms, the variants affected neither the stability nor the bioenergetics of the mitochondrial complex.

Dominant NARS1 mutations causing axonal Charcot-Marie-Tooth disease expand NARS1-associated diseases. Beijer D, Marte S, Li JC et al. Brain Commun. 2024 Mar 8;6(2):fcae070.

 

Alternative splicing expands the clinical spectrum of NDUFS6-related mitochondrial disorders. Armirola-Ricaurte C, Zonnekein N, Koutsis G et al. Genet Med. 2024 Mar 5:101117.