Disrupted SOX10 regulation of GJC2 transcription causes Pelizaeus-Merzbacher-like disease

Ann Neurol. 2010 Aug;68(2):250-4. doi: 10.1002/ana.22022.


Mutations in the gap junction protein gamma-2 gene, GJC2, cause a central hypomyelinating disorder; Pelizaeus-Merzbacher-like disease (PMLD; MIM311601). Using a homozygosity mapping and positional candidate gene approach, we identified a homozygous mutation (c.-167A>G) within the GJC2 promoter at a potent SOX10 binding site in a patient with mild PMLD. Functionally, this mutation completely abolished the SOX10 binding and attenuated GJC2 promoter activity. These findings suggest not only that the SOX10-to-GJC2 transcriptional dysregulation is a cause of PMLD, but also that GJC2 may be in part responsible for the central hypomyelination caused by SOX10 mutations.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Connexins / genetics*
  • Connexins / metabolism*
  • Female
  • Humans
  • Mutation
  • Myelin Sheath / genetics
  • Myelin Sheath / metabolism
  • Pelizaeus-Merzbacher Disease / genetics*
  • Pelizaeus-Merzbacher Disease / metabolism*
  • Pelizaeus-Merzbacher Disease / pathology
  • Regulatory Elements, Transcriptional / genetics
  • SOXE Transcription Factors / genetics
  • SOXE Transcription Factors / physiology*
  • Transcription, Genetic* / genetics


  • Connexins
  • SOX10 protein, human
  • SOXE Transcription Factors
  • connexin 47