Author:
Abati Elena,Manini Arianna,Velardo Daniele,Del Bo Roberto,Napoli Laura,Rizzo Federica,Moggio Maurizio,Bresolin Nereo,Bellone Emilia,Bassi Maria Teresa,D’Angelo Maria Grazia,Comi Giacomo Pietro,Corti Stefania
Abstract
AbstractCharcot–Marie–Tooth disease type 2A (CMT2A) is a rare inherited axonal neuropathy caused by mutations in MFN2 gene, which encodes Mitofusin 2, a transmembrane protein of the outer mitochondrial membrane. We performed a cross-sectional analysis on thirteen patients carrying mutations in MFN2, from ten families, describing their clinical and genetic characteristics. Evaluated patients presented a variable age of onset and a wide phenotypic spectrum, with most patients presenting a severe phenotype. A novel heterozygous missense variant was detected, p.K357E. It is located at a highly conserved position and predicted as pathogenic by in silico tools. At a clinical level, the p.K357E carrier shows a severe sensorimotor axonal neuropathy. In conclusion, our work expands the genetic spectrum of CMT2A, disclosing a novel mutation and its related clinical effect, and provides a detailed description of the clinical features of a cohort of patients with MFN2 mutations. Obtaining a precise genetic diagnosis in affected families is crucial both for family planning and prenatal diagnosis, and in a therapeutic perspective, as we are entering the era of personalized therapy for genetic diseases.
Funder
Ministero della Salute
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Fondazione per la Ricerca Biomedica
Fondazione Telethon
Publisher
Springer Science and Business Media LLC
Cited by
8 articles.
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