Human Genetics

, Volume 116, Issue 1, pp 23–27

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

  • Kazuki Kijima
  • Chikahiko Numakura
  • Hiroko Izumino
  • Kazuo Umetsu
  • Atsuo Nezu
  • Toshihide Shiiki
  • Masafumi Ogawa
  • Yoshito Ishizaki
  • Takeshi Kitamura
  • Yasunobu Shozawa
  • Kiyoshi Hayasaka
Original Investigation

DOI: 10.1007/s00439-004-1199-2

Cite this article as:
Kijima, K., Numakura, C., Izumino, H. et al. Hum Genet (2005) 116: 23. doi:10.1007/s00439-004-1199-2

Abstract

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.

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Kazuki Kijima
    • 1
  • Chikahiko Numakura
    • 1
  • Hiroko Izumino
    • 1
  • Kazuo Umetsu
    • 2
  • Atsuo Nezu
    • 3
  • Toshihide Shiiki
    • 4
  • Masafumi Ogawa
    • 5
  • Yoshito Ishizaki
    • 6
  • Takeshi Kitamura
    • 7
  • Yasunobu Shozawa
    • 8
  • Kiyoshi Hayasaka
    • 1
  1. 1.Department of PediatricsYamagata University School of MedicineYamagataJapan
  2. 2.Department of Forensic MedicineYamagata University School of MedicineYamagataJapan
  3. 3.Department of PediatricsYokohama City University Medical CenterYokohamaJapan
  4. 4.Tokyo Children’s Habilitation HospitalTokyoJapan
  5. 5.Department of NeurologyNational Center Hospital for Mental, Nervous, and Muscular Disorders, National Center of Neurology and PsychiatryTokyoJapan
  6. 6.Department of Pediatric NeurologyFukuoka Children’s Hospital Medical CenterFukuokaJapan
  7. 7.Department of NeurologySaiseikai Hiroshima HospitalHiroshimaJapan
  8. 8.Department of NeurologyTeikyo University School of MedicineTokyoJapan