Mitochondrial complex I deficiency in GDAP1-related autosomal dominant Charcot-Marie-Tooth disease (CMT2K)

Neurogenetics. 2009 Apr;10(2):145-50. doi: 10.1007/s10048-008-0166-9. Epub 2008 Dec 17.


Mutations in GDAP1, an outer mitochondrial membrane protein responsible for recessive Charcot-Marie-Tooth disease (CMT4A), have also been associated with CMT2K, a dominant form of the disease. The three CMT2K patients we studied carried a novel dominant GDAP1 mutation, C240Y (c.719G > A). Mitochondrial respiratory chain complex I activity in fibroblasts from CMT2K patients was 40% lower than in controls, whereas the tubular mitochondria were 33% larger in diameter and the mitochondrial mass was 20% greater. Thus, besides the regulatory role GDAP1 plays in mitochondrial network dynamics, it may also be involved in energy production and in the control of mitochondrial volume.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Charcot-Marie-Tooth Disease / genetics*
  • Charcot-Marie-Tooth Disease / physiopathology
  • DNA Mutational Analysis
  • Electron Transport Complex I / deficiency*
  • Electron Transport Complex I / genetics
  • Electron Transport Complex I / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mitochondria* / genetics
  • Mitochondria* / metabolism
  • Mutation, Missense
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Oxidative Phosphorylation
  • Pedigree


  • GDAP protein
  • Nerve Tissue Proteins
  • Electron Transport Complex I