title: MFN2 mutation distribution and genotype/phenotype correlation in Charcot-Marie-Tooth type 2.
abstract: Mutations in mitofusin 2 (MFN2) have been reported in Charcot-Marie-Tooth type 2 (CMT2) families. To study the distribution of mutations in MFN2 we screened 323 families and isolated patients with distinct CMT phenotypes. In 29 probands, we identified 22 distinct MFN2 mutations, and 14 of these mutations have not been reported before. All mutations were located in the cytoplasmic domains of the MFN2 protein. Patients presented with a classical but rather severe CMT phenotype, since 28% of them were wheelchair-dependent. Some had additional features as optic atrophy. Most patients had an early onset and severe disease status, whereas a smaller group experienced a later onset and milder disease course. Electrophysiological data showed in the majority of patients normal to slightly reduced nerve conduction velocities with often severely reduced amplitudes of the compound motor and sensory nerve action potentials. Examination of sural nerve specimens showed loss of large myelinated fibres and degenerative mitochondrial changes. In patients with a documented family history of CMT2 the frequency of MFN2 mutations was 33% indicating that MFN2 mutations are a major cause in this population.
authors.affiliation: Peripheral Neuropathy Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology Antwerpen, Belgium.
authors.forename: Kristien
authors.initials: K
authors.lastname: Verhoeven
authors.forename: Kristl G
authors.initials: KG
authors.lastname: Claeys
authors.forename: Stephan
authors.initials: S
authors.lastname: Züchner
authors.forename: J Michael
authors.initials: JM
authors.lastname: Schröder
authors.forename: Joachim
authors.initials: J
authors.lastname: Weis
authors.forename: Chantal
authors.initials: C
authors.lastname: Ceuterick
authors.forename: Albena
authors.initials: A
authors.lastname: Jordanova
authors.forename: Eva
authors.initials: E
authors.lastname: Nelis
authors.forename: Els
authors.initials: E
authors.lastname: De Vriendt
authors.forename: Matthias
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authors.lastname: Van Hul
authors.forename: Pavel
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authors.lastname: Seeman
authors.forename: Radim
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authors.lastname: Mazanec
authors.forename: Gulam Mustafa
authors.initials: GM
authors.lastname: Saifi
authors.forename: Kinga
authors.initials: K
authors.lastname: Szigeti
authors.forename: Pedro
authors.initials: P
authors.lastname: Mancias
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Butler
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kochanski
authors.forename: Barbara
authors.initials: B
authors.lastname: Ryniewicz
authors.forename: Jan
authors.initials: J
authors.lastname: De Bleecker
authors.forename: Peter
authors.initials: P
authors.lastname: Van den Bergh
authors.forename: Christine
authors.initials: C
authors.lastname: Verellen
authors.forename: Rudy
authors.initials: R
authors.lastname: Van Coster
authors.forename: Nathalie
authors.initials: N
authors.lastname: Goemans
authors.forename: Michaela
authors.initials: M
authors.lastname: Auer-Grumbach
authors.forename: Wim
authors.initials: W
authors.lastname: Robberecht
authors.forename: Vedrana
authors.initials: V
authors.lastname: Milic Rasic
authors.forename: Yoram
authors.initials: Y
authors.lastname: Nevo
authors.forename: Ivajlo
authors.initials: I
authors.lastname: Tournev
authors.forename: Velina
authors.initials: V
authors.lastname: Guergueltcheva
authors.forename: Filip
authors.initials: F
authors.lastname: Roelens
authors.forename: Peter
authors.initials: P
authors.lastname: Vieregge
authors.forename: Paolo
authors.initials: P
authors.lastname: Vinci
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Moreno
authors.forename: H-J
authors.initials: HJ
authors.lastname: Christen
authors.forename: Michael E
authors.initials: ME
authors.lastname: Shy
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
authors.forename: Jeffery M
authors.initials: JM
authors.lastname: Vance
authors.forename: Peter
authors.initials: P
authors.lastname: De Jonghe
authors.forename: Vincent
authors.initials: V
authors.lastname: Timmerman
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004594:Electrophysiology; D020558:GTP Phosphohydrolases; D005838:Genotype; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008854:Microscopy, Electron; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D012720:Severity of Illness Index; D013497:Sural Nerve / Q000648:ultrastructure
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human