MFN2 mutation distribution and genotype/phenotype correlation in Charcot-Marie-Tooth type 2

Kristien Verhoeven, Kristl G. Claeys, Stephan L Zuchner, 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 BerghChristine 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, Vincent Timmerman

Research output: Contribution to journalArticle

256 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2093-2102
Number of pages10
JournalBrain
Volume129
Issue number8
DOIs
StatePublished - Aug 1 2006
Externally publishedYes

Fingerprint

Genetic Association Studies
Tooth
Mutation
Phenotype
Optic Atrophy
Sural Nerve
Wheelchairs
Neural Conduction
Action Potentials
Population
Proteins

Keywords

  • Charcot-Marie-Tooth type 2
  • Genotype-phenotype correlation
  • Mitofusin 2

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Verhoeven, K., Claeys, K. G., Zuchner, S. L., Schröder, J. M., Weis, J., Ceuterick, C., ... Timmerman, V. (2006). MFN2 mutation distribution and genotype/phenotype correlation in Charcot-Marie-Tooth type 2. Brain, 129(8), 2093-2102. https://doi.org/10.1093/brain/awl126

MFN2 mutation distribution and genotype/phenotype correlation in Charcot-Marie-Tooth type 2. / Verhoeven, Kristien; Claeys, Kristl G.; Zuchner, Stephan L; Schröder, J. Michael; Weis, Joachim; Ceuterick, Chantal; Jordanova, Albena; Nelis, Eva; De Vriendt, Els; Van Hul, Matthias; Seeman, Pavel; Mazanec, Radim; Saifi, Gulam Mustafa; Szigeti, Kinga; Mancias, Pedro; Butler, Ian J.; Kochanski, Andrzej; Ryniewicz, Barbara; De Bleecker, Jan; Van Den Bergh, Peter; Verellen, Christine; Van Coster, Rudy; Goemans, Nathalie; Auer-Grumbach, Michaela; Robberecht, Wim; Milic Rasic, Vedrana; Nevo, Yoram; Tournev, Ivajlo; Guergueltcheva, Velina; Roelens, Filip; Vieregge, Peter; Vinci, Paolo; Moreno, Maria Teresa; Christen, H. J.; Shy, Michael E.; Lupski, James R.; Vance, Jeffery M; De Jonghe, Peter; Timmerman, Vincent.

In: Brain, Vol. 129, No. 8, 01.08.2006, p. 2093-2102.

Research output: Contribution to journalArticle

Verhoeven, K, Claeys, KG, Zuchner, SL, Schröder, JM, Weis, J, Ceuterick, C, Jordanova, A, Nelis, E, De Vriendt, E, Van Hul, M, Seeman, P, Mazanec, R, Saifi, GM, Szigeti, K, Mancias, P, Butler, IJ, Kochanski, A, Ryniewicz, B, De Bleecker, J, Van Den Bergh, P, Verellen, C, Van Coster, R, Goemans, N, Auer-Grumbach, M, Robberecht, W, Milic Rasic, V, Nevo, Y, Tournev, I, Guergueltcheva, V, Roelens, F, Vieregge, P, Vinci, P, Moreno, MT, Christen, HJ, Shy, ME, Lupski, JR, Vance, JM, De Jonghe, P & Timmerman, V 2006, 'MFN2 mutation distribution and genotype/phenotype correlation in Charcot-Marie-Tooth type 2', Brain, vol. 129, no. 8, pp. 2093-2102. https://doi.org/10.1093/brain/awl126
Verhoeven K, Claeys KG, Zuchner SL, Schröder JM, Weis J, Ceuterick C et al. MFN2 mutation distribution and genotype/phenotype correlation in Charcot-Marie-Tooth type 2. Brain. 2006 Aug 1;129(8):2093-2102. https://doi.org/10.1093/brain/awl126
Verhoeven, Kristien ; Claeys, Kristl G. ; Zuchner, Stephan L ; Schröder, J. Michael ; Weis, Joachim ; Ceuterick, Chantal ; Jordanova, Albena ; Nelis, Eva ; De Vriendt, Els ; Van Hul, Matthias ; Seeman, Pavel ; Mazanec, Radim ; Saifi, Gulam Mustafa ; Szigeti, Kinga ; Mancias, Pedro ; Butler, Ian J. ; Kochanski, Andrzej ; Ryniewicz, Barbara ; De Bleecker, Jan ; Van Den Bergh, Peter ; Verellen, Christine ; Van Coster, Rudy ; Goemans, Nathalie ; Auer-Grumbach, Michaela ; Robberecht, Wim ; Milic Rasic, Vedrana ; Nevo, Yoram ; Tournev, Ivajlo ; Guergueltcheva, Velina ; Roelens, Filip ; Vieregge, Peter ; Vinci, Paolo ; Moreno, Maria Teresa ; Christen, H. J. ; Shy, Michael E. ; Lupski, James R. ; Vance, Jeffery M ; De Jonghe, Peter ; Timmerman, Vincent. / MFN2 mutation distribution and genotype/phenotype correlation in Charcot-Marie-Tooth type 2. In: Brain. 2006 ; Vol. 129, No. 8. pp. 2093-2102.
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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.",
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AU - Claeys, Kristl G.

AU - Zuchner, Stephan L

AU - Schröder, J. Michael

AU - Weis, Joachim

AU - Ceuterick, Chantal

AU - Jordanova, Albena

AU - Nelis, Eva

AU - De Vriendt, Els

AU - Van Hul, Matthias

AU - Seeman, Pavel

AU - Mazanec, Radim

AU - Saifi, Gulam Mustafa

AU - Szigeti, Kinga

AU - Mancias, Pedro

AU - Butler, Ian J.

AU - Kochanski, Andrzej

AU - Ryniewicz, Barbara

AU - De Bleecker, Jan

AU - Van Den Bergh, Peter

AU - Verellen, Christine

AU - Van Coster, Rudy

AU - Goemans, Nathalie

AU - Auer-Grumbach, Michaela

AU - Robberecht, Wim

AU - Milic Rasic, Vedrana

AU - Nevo, Yoram

AU - Tournev, Ivajlo

AU - Guergueltcheva, Velina

AU - Roelens, Filip

AU - Vieregge, Peter

AU - Vinci, Paolo

AU - Moreno, Maria Teresa

AU - Christen, H. J.

AU - Shy, Michael E.

AU - Lupski, James R.

AU - Vance, Jeffery M

AU - De Jonghe, Peter

AU - Timmerman, Vincent

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