Journal article
MFN2 mutation distribution and genotype/ phenotype correlation in Charcot-Marie-Tooth type 2
Brain (London, England : 1878), Vol.129(8), pp.2093-2102
2006
DOI: 10.1093/brain/awl126
PMID: 16714318
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.
Details
- Title: Subtitle
- MFN2 mutation distribution and genotype/ phenotype correlation in Charcot-Marie-Tooth type 2
- Creators
- Kristien VERHOEVEN - Peripheral Neuropathy Group, Flanders Interuniversity Institute for Biotechnology, BelgiumKristl G CLAEYS - Neurogenetics Group, Department of Molecular Genetic, Flanders Interuniversity Institute for Biotechnology, BelgiumPavel SEEMAN - DNA Laboratory, Department of Child Neurology, Second School of Medicine, Charles University Prague, Prague, Czech RepublicRadim MAZANEC - Department of Neurology, Second School of Medicine, Charles University Prague, Prague, Czech RepublicGulam Mustafa SAIFI - Department of Molecular and Human Genetics, Baylor College of Medicine, United StatesKinga SZIGETI - Department of Molecular and Human Genetics, Baylor College of Medicine, United StatesPedro MANCIAS - Department of Neurology, The University of Texas Health Science Centre at Houston Medical School, Houston, TX, United StatesIan J BUTLER - Department of Neurology, The University of Texas Health Science Centre at Houston Medical School, Houston, TX, United StatesAndrzej KOCHANSKI - Neuromuscular Unit, Mossakowski Medical Research Center, Medical University, Warszawa, PolandBarbara RYNIEWICZ - Department of Neurology, Medical University, Warszawa, PolandJan DE BLEECKER - Department of Neurology, University Hospital of Gent, Gent, BelgiumPeter VAN DEN BERGH - Division of Neurology, University Hospital Saint-Luc, BelgiumStephan ZUCHNER - Center for Human Genetics, Duke University Medical Center, Durham, NC, United StatesChristine VERELLEN - Center of Human Genetics, Catholic University of Louvain, Brussels, BelgiumRudy VAN COSTER - Department of Child Neurology, University Hospital of Gent, Gent, BelgiumNathalie GOEMANS - Child Neurology, University of Leuven, Campus Gasthuisberg, Leuven, BelgiumMichaela AUER-GRUMBACH - Institute of Medical Biology and Human Genetics, Department of Internal Medicine, Diabetes and Metabolism, Medical University Graz, Graz, AustriaWim ROBBERECHT - Laboratory for Neurobiology, University of Leuven, Campus Gasthuisberg, Leuven, BelgiumVedrana Milic RASIC - Peripheral Neuropathy Group, Flanders Interuniversity Institute for Biotechnology, BelgiumYoram NEVO - Peripheral Neuropathy Group, Flanders Interuniversity Institute for Biotechnology, BelgiumIvajlo TOURNEV - Department of Molecular Pathology, Sofia Medical University, Sofia, BulgariaVelina GUERGUELTCHEVA - Department of Molecular Pathology, Sofia Medical University, Sofia, BulgariaFilip ROELENS - Division of Pediatric Neurology, 'Heilig-Hart' Hospital Roeselare, Roeselare, BelgiumJ. Michael SCHRÖDER - Department of Neuropathology, University Hospital, RWTH Aachen, Aachen, GermanyPeter VIEREGGE - Department of Neurology, Klinikum Lippe-Lemgo, GermanyPaolo VINCI - Peripheral Neuropathy Group, Flanders Interuniversity Institute for Biotechnology, BelgiumMaria Teresa MORENO - Peripheral Neuropathy Group, Flanders Interuniversity Institute for Biotechnology, BelgiumH.-J CHRISTEN - Department of Neuropediatrics, Children's Hospital 'Auf der Bult', Hannover, GermanyMichael E SHY - Department of Neurology, Center for Molecular Medicine and Genetics, Wayne State University, Detroit, United StatesJames R LUPSKI - Department of Molecular and Human Genetics, Baylor College of Medicine, United StatesJeffery M VANCE - Center for Human Genetics, Duke University Medical Center, Durham, NC, United StatesPeter DE DJONGHE - Neurogenetics Group, Department of Molecular Genetic, Flanders Interuniversity Institute for Biotechnology, BelgiumVincent TIMMERMAN - Peripheral Neuropathy Group, Flanders Interuniversity Institute for Biotechnology, BelgiumJoachim WEIS - Department of Neuropathology, University Hospital, RWTH Aachen, Aachen, GermanyChantal CEUTERICK - Laboratory of Neuropathology, Institute Born Bunge, University of Antwerp, BelgiumAlbena JORDANOVA - Peripheral Neuropathy Group, Flanders Interuniversity Institute for Biotechnology, BelgiumEva NELIS - Neurogenetics Group, Department of Molecular Genetic, Flanders Interuniversity Institute for Biotechnology, BelgiumEls DE VRIENDT - Peripheral Neuropathy Group, Flanders Interuniversity Institute for Biotechnology, BelgiumMatthias VAN HUL - Peripheral Neuropathy Group, Flanders Interuniversity Institute for Biotechnology, Belgium
- Resource Type
- Journal article
- Publication Details
- Brain (London, England : 1878), Vol.129(8), pp.2093-2102
- Publisher
- Oxford University Press; Oxford
- DOI
- 10.1093/brain/awl126
- PMID
- 16714318
- ISSN
- 0006-8950
- eISSN
- 1460-2156
- Language
- English
- Date published
- 2006
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
- Record Identifier
- 9984013114902771
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