title: Characterizing the phenotypic manifestations of MFN2 R104W mutation in Charcot-Marie-Tooth type 2.
abstract: Mutations of the mitofusin 2 (MFN2) gene have been reported to be the most common cause of the axonal form of Charcot-Marie-Tooth disease (CMT). The aim of this study was to describe a de novo MFN2 p.R104W mutation and characterize the associated phenotype. We screened the entire coding region of MFN2 gene and characterized its clinical phenotype, nerve conduction studies and sural nerve biopsy. Neuropsychological tests and brain MRI were also performed. A de novo mutation was found in exon 4 (c.310C>T; p.R104W). In addition to a severe and early onset axonal neuropathy, the patient presented learning problems, obesity, glucose intolerance, leukoencephalopathy, brain atrophy and evidence of myelin involvement and mitochondrial structural changes on sural nerve biopsy. These results suggest that MFN2 p.R104W mutation is as a hot-spot for MFN2 gene associated to a large and complex range of phenotypes.
authors.affiliation: Department of Neurosciences and Behavior Sciences, School of Medicine of Ribeirão Preto, University of São Paulo, USP, Brazil.
authors.forename: Adriana Borges
authors.initials: AB
authors.lastname: Genari
authors.forename: Vinícius Horácio Stefani
authors.initials: VH
authors.lastname: Borghetti
authors.forename: Silmara Paula
authors.initials: SP
authors.lastname: Gouvêa
authors.forename: Keity Cristina
authors.initials: KC
authors.lastname: Bueno
authors.forename: Patrícia Leila
authors.initials: PL
authors.lastname: dos Santos
authors.forename: Antonio Carlos
authors.initials: AC
authors.lastname: dos Santos
authors.forename: Amilton Antunes
authors.initials: AA
authors.lastname: Barreira
authors.forename: Charles Marques
authors.initials: CM
authors.lastname: Lourenço
authors.forename: Wilson
authors.initials: W
authors.lastname: Marques
mesh_terms: D000293:Adolescent; D001706:Biopsy; D001921:Brain / Q000473:pathology; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D020558:GTP Phosphohydrolases; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009431:Neural Conduction / Q000502:physiology; D009483:Neuropsychological Tests; D010641:Phenotype; D013497:Sural Nerve / Q000473:pathology
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human