title: Spectrum and frequencies of mutations in the MFN2 gene and its phenotypical expression in Czech hereditary motor and sensory neuropathy type II patients.
abstract: The axonal type of Charcot‑Marie‑Tooth (CMT) disorders is genetically heterogeneous, therefore the causal mutation is unlikely to be observed, even in clinically well characterized patients. Mitofusin‑2 (MFN2) gene mutations are the most frequent cause of axonal CMT disorders in a number of populations. There are two phenotypes; early onset, which is severe and late onset, which is a milder phenotype. A cohort of 139 unrelated Czech patients with axonal neuropathy was selected for sequencing and multiplex ligation-dependent probe amplification analysis (MLPA) testing of the MFN2 gene. A total of 11 MFN2 mutations were detected, with eight pathogenic mutations and three potentially rare benign polymorphisms. MLPA testing in 64 unrelated patients did not detect any exon duplication or deletion. The frequency of the pathogenic mutations detected in Czech hereditary motor and sensory neuropathy type II (HMSN II) patients was 7.2%. Early onset was more frequent among pathogenic mutation cases. Therefore we propose to examine the MFN2 gene mainly in patients with early and severe axonal CMT.
authors.affiliation: DNA Laboratory, Department of Child Neurology, Charles University Second Medical School and University Hospital Motol, Prague 15006, Czech Republic.
authors.forename: Dana Šafka
authors.initials: DŠ
authors.lastname: Brožková
authors.forename: Jan
authors.initials: J
authors.lastname: Posádka
authors.forename: Petra
authors.initials: P
authors.lastname: Laššuthová
authors.forename: Radim
authors.initials: R
authors.lastname: Mazanec
authors.forename: Jana
authors.initials: J
authors.lastname: Haberlová
authors.forename: Dana
authors.initials: D
authors.lastname: Sišková
authors.forename: Iva
authors.initials: I
authors.lastname: Sakmaryová
authors.forename: Jana
authors.initials: J
authors.lastname: Neupauerová
authors.forename: Pavel
authors.initials: P
authors.lastname: Seeman
mesh_terms: D002607:Charcot-Marie-Tooth Disease / Q000235:genetics*; D018153:Czech Republic; D005091:Exons / Q000235:genetics; D005190:Family; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006801:Humans; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D059645:Mutation Rate; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human