Original Investigation

Human Genetics

, Volume 116, Issue 1, pp 23-27

First online:

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

  • Kazuki KijimaAffiliated withDepartment of Pediatrics, Yamagata University School of Medicine
  • , Chikahiko NumakuraAffiliated withDepartment of Pediatrics, Yamagata University School of Medicine
  • , Hiroko IzuminoAffiliated withDepartment of Pediatrics, Yamagata University School of Medicine
  • , Kazuo UmetsuAffiliated withDepartment of Forensic Medicine, Yamagata University School of Medicine
  • , Atsuo NezuAffiliated withDepartment of Pediatrics, Yokohama City University Medical Center
  • , Toshihide ShiikiAffiliated withTokyo Children’s Habilitation Hospital
  • , Masafumi OgawaAffiliated withDepartment of Neurology, National Center Hospital for Mental, Nervous, and Muscular Disorders, National Center of Neurology and Psychiatry
  • , Yoshito IshizakiAffiliated withDepartment of Pediatric Neurology, Fukuoka Children’s Hospital Medical Center
  • , Takeshi KitamuraAffiliated withDepartment of Neurology, Saiseikai Hiroshima Hospital
    • , Yasunobu ShozawaAffiliated withDepartment of Neurology, Teikyo University School of Medicine
    • , Kiyoshi HayasakaAffiliated withDepartment of Pediatrics, Yamagata University School of Medicine Email author 

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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-ß (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.