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.

Clinical and genetic features of a cohort of patients with MFN2-related neuropathy / E. Abati, A. Manini, D. Velardo, R. Del Bo, L. Napoli, F. Rizzo, M. Moggio, N. Bresolin, E. Bellone, M.T. Bassi, M.G. D'Angelo, G.P. Comi, S. Corti. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 12:1(2022 Apr 13), pp. 6181.1-6181.8. [10.1038/s41598-022-10220-0]

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

E. Abati
Primo
;
A. Manini;R. Del Bo;F. Rizzo;N. Bresolin;E. Bellone;M.T. Bassi;M.G. D'Angelo;G.P. Comi
Penultimo
;
S. Corti
Ultimo
2022

Abstract

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.
cross-sectional studies; humans; phenotype; Charcot-Marie-tooth disease; GTP phosphohydrolases; mitochondrial proteins
Settore MED/26 - Neurologia
13-apr-2022
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/925376
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