J Med Genet 45:161-166 doi:10.1136/jmg.2007.052332
  • Letters to JMG

A novel missense mutation in GJB2 disturbs gap junction protein transport and causes focal palmoplantar keratoderma with deafness

  1. E A de Zwart-Storm1,3,
  2. H Hamm2,
  3. J Stoevesandt2,
  4. P M Steijlen1,
  5. P E Martin3,
  6. M van Geel1,
  7. M A M van Steensel1
  1. 1
    Department of Dermatology, Maastricht University Centre for Molecular Dermatology (MUCMD) and GROW - School for Oncology and Developmental Biology, University Hospital Maastricht, The Netherlands
  2. 2
    Department of Dermatology, University of Würzburg, Germany
  3. 3
    Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow, UK
  1. E A de Zwart-Storm, MD, Department of Dermatology, Maastricht University Centre for Molecular Dermatology, Research Institute for Growth & Development (GROW), University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands; edz{at}
  • Received 13 June 2007
  • Revised 10 October 2007
  • Accepted 19 October 2007
  • Published Online First 9 November 2007


Gap junctions are intercellular channels that mediate rapid intercellular communication. They consist of connexins, small transmembrane proteins that belong to a large family found throughout the animal kingdom. In the skin, several connexins are expressed and are involved in the regulation of epidermal growth and differentiation. One of the skin expressed gap junction genes is GJB2, which codes for connexin 26 and is associated with a wide variety of keratinisation disorders. Here, we report on a family with a novel GJB2 mutation (p.His73Arg) causing a syndrome of focal palmoplantar keratoderma with severe progressive sensorineural hearing impairment, a phenotype reminiscent of Vohwinkel syndrome. Using fluorescent connexin fusion proteins, we show that the mutation induces a transport defect similar to that found for the Vohwinkel syndrome mutation p.Asp66His. Co-transfection into cells expressing wild type connexin26 shows that the mutant has a dominant negative effect on connexin trafficking. We suggest that there may be a weak genotype–phenotype correlation for mutations in GJB2.


  • Competing interests: None declared.

  • Patient consent: Parental informed consent was obtained for publications of the persons’ details in this report