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Clinical and genetic features of a cohort of patients with MFN2-related neuropathy

Charcot–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 te...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9008012/
https://www.ncbi.nlm.nih.gov/pubmed/35418194
http://dx.doi.org/10.1038/s41598-022-10220-0
Descripción
Sumario:Charcot–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.