Point mutation associated with X-linked dominant Charcot-Marie-Tooth disease impairs the P2 promoter activity of human connexin-32 gene

Brain Res Mol Brain Res. 2000 May 31;78(1-2):146-53. doi: 10.1016/s0169-328x(00)00087-5.


Many lines of evidence suggest that connexin-32 gap junction is involved in the exchange of information and metabolites in the peripheral nervous system. It has been shown that connexin-32 protein and mRNA are expressed in Schwann cells that function as myelinating cells of the peripheral nervous system. The physiological importance of connexin-32 gap junctions in regulating the normal function of myelinating Schwann cell is indicated by recent findings that X-linked dominant Charcot-Marie-Tooth disease, a hereditary peripheral neuropathy, is associated with the mutations of connexin-32 gene. Recently, we encountered a Taiwanese family affected with X-linked dominant Charcot-Marie-Tooth neuropathy. Therefore, we investigated the possible mutation in the coding and noncoding regions of the connexin-32 gene of affected members of this family. Our results suggest that a G-to-A transition at the position -215 (in relation to the transcription initiation site) of the nerve-specific P2 promoter region is associated with the pathogenesis of X-linked dominant Charcot-Marie-Tooth disease. Further experiments using the promoter assay indicate that G-to-A mutation at the position -215 greatly impairs the transcriptional activity of connexin-32 P2 promoter. These findings propose that a reduced expression of connexin-32 mRNA and protein in the myelin sheath could be responsible for the development of X-linked dominant Charcot-Marie-Tooth neuropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Charcot-Marie-Tooth Disease / genetics*
  • Connexins / genetics*
  • Cricetinae
  • Family Health
  • Female
  • Gene Expression / physiology
  • Genes, Dominant
  • Genes, Reporter
  • Genetic Linkage*
  • Glioma
  • Humans
  • Intercellular Junctions / physiology
  • Luciferases
  • Male
  • Membrane Potentials / genetics
  • Neurons / chemistry
  • Neurons / physiology
  • Patch-Clamp Techniques
  • Pedigree
  • Point Mutation*
  • Promoter Regions, Genetic / genetics*
  • Schwann Cells / physiology
  • Taiwan
  • Transcriptional Activation / genetics
  • Tumor Cells, Cultured
  • X Chromosome*


  • Connexins
  • connexin 32
  • Luciferases