Mitochondrial GTPase mitofusin 2 mutation in Charcot-Marie-Tooth neuropathy type 2A

Hum Genet. 2005 Jan;116(1-2):23-7. doi: 10.1007/s00439-004-1199-2. Epub 2004 Nov 11.


Charcot-Marie-Tooth disease (CMT) has been classified into two types, CMT1 and CMT2, demyelinating and axonal forms, respectively. CMT2 has been further subdivided into eight groups by linkage studies. CMT2A is linked to chromosome 1p35-p36 and mutation in the kinesin family member 1B-beta (KIF1B) gene had been reported in one pedigree. However, no mutation in KIF1B was detected in other pedigrees with CMT2A and the mutations in the mitochondrial fusion protein mitofusin 2 (MFN2) gene were recently detected in those pedigrees. MFN2, a mitochondrial transmembrane GTPase, regulates the mitochondrial network architecture by fusion of mitochondria. We studied MFN2 in 81 Japanese patients with axonal or unclassified CMT and detected seven mutations in seven unrelated patients. Six of them were novel and one of them was a de novo mutation. Most mutations locate within or immediately upstream of the GTPase domain or within two coiled-coil domains, which are critical for the functioning or mitochondrial targeting of MFN2. Formation of a mitochondrial network would be required to maintain the functional peripheral nerve axon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Charcot-Marie-Tooth Disease / enzymology
  • Charcot-Marie-Tooth Disease / genetics*
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • GTP Phosphohydrolases / genetics*
  • Heterozygote
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Mitochondria / enzymology
  • Mitochondria / genetics
  • Mitochondrial Proteins / genetics*
  • Mutation


  • Membrane Proteins
  • Mitochondrial Proteins
  • GTP Phosphohydrolases
  • MFN2 protein, human