Journal Article

<i>MFN2</i> mutation distribution and genotype/phenotype correlation in Charcot–Marie–Tooth type 2

Kristien Verhoeven, Kristl G. Claeys, Stephan Züchner, J. Michael Schröder, Joachim Weis, Chantal Ceuterick, Albena Jordanova, Eva Nelis, Els De Vriendt, Matthias Van Hul, Pavel Seeman, Radim Mazanec, Gulam Mustafa Saifi, Kinga Szigeti, Pedro Mancias, Ian J. Butler, Andrzej Kochanski, Barbara Ryniewicz, Jan De Bleecker, Peter Van den Bergh, Christine Verellen, Rudy Van Coster, Nathalie Goemans, Michaela Auer-Grumbach, Wim Robberecht, Vedrana Milic Rasic, Yoram Nevo, Ivajlo Tournev, Velina Guergueltcheva, Filip Roelens, Peter Vieregge, Paolo Vinci, Maria Teresa Moreno, H.-J. Christen, Michael E. Shy, James R. Lupski, Jeffery M. Vance, Peter De Jonghe and Vincent Timmerman

in Brain

Published on behalf of The Guarantors of Brain

Volume 129, issue 8, pages 2093-2102
ISSN: 0006-8950
Published online May 2006 | e-ISSN: 1460-2156 | DOI: http://dx.doi.org/10.1093/brain/awl126
MFN2 mutation distribution and genotype/phenotype correlation in Charcot–Marie–Tooth type 2

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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.

Keywords: Charcot–Marie–Tooth type 2; mitofusin 2; genotype–phenotype correlation

Journal Article.  5790 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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