Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News & Views
  • Published:

One connexin, two diseases

Nature Genetics volume 20, pages 319–320 (1998)Cite this article

The complexity of human genetic disease continues to confuse, and it sometimes seems remarkable that so much progress has been made in identifying disease genes when subsequent work shows that the story is much more involved than was at first imagined. In this issue, one group reports on the genetic cause of a skin disease1 and another, of hearing loss2. Each disorder is attributed to mutations in the same gene, which poses the question: how can mutations in one gene lead to such diverse disorders?

Connexin genes have long been aetiologic candidates for skin disorders, because many are expressed in the skin and some are upregulated in damaged or psoriatic skin. On page 366, Gabriela Richard and colleagues provide the first description of mutations in a connexin gene (GJB3) causing a skin disorder—in this case erythrokeratodermia variabilis1. This dominant disease is characterized by variable regions of hyperkeratosis and transient red patches. GJB3 was a good candidate gene, as its chromosomal position colocalizes with the disease locus and it is expressed in hair follicles and skin, with high levels of expression in differentiating keratinocytes5,6,7. Three missense mutations were detected; two affect the same amino acid residue at position 12 at the N terminus, while the third results in a substitution in the second transmembrane domain (Fig. 2).

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Diagram of a gap junction.
Figure 2: Predicted arrangement of the connexin 31 molecule within the cell membrane.

References

  1. Richard, G. et al. Nature Genet. 20, 366– 369 (1998).

    Article  CAS  Google Scholar 

  2. Xia, J. et al. Nature Genet. 20, 370–373 (1998).

    Article  CAS  Google Scholar 

  3. Bruzzone, R., White, T.W. & Paul, D.L. Eur. J. Biochem. 238, 1– 27 (1996).

    Article  CAS  Google Scholar 

  4. Goodenough, D.A., Goliger, J.A. & Paul, D.L. Annu. Rev. Biochem. 65, 475 –502 (1996).

    Article  CAS  Google Scholar 

  5. Hoh, J.H., John, S.A. & Revel, J.P. J. Biol. Chem. 266, 6524– 6531 (1991).

    CAS  PubMed  Google Scholar 

  6. Butterweck, A., Elfgang, C., Willecke, K. & Traub, O. Eur. J. Cell Biol. 65, 152–163 (1994).

    CAS  PubMed  Google Scholar 

  7. Brissette, J.L., Kumar, N.M., Gilula, N.B., Hall, J.E. & Dotto, G.P. Proc. Natl Acad. Sci. USA 91, 6453–6457 (1994).

    Article  CAS  Google Scholar 

  8. Bergoffen, J. et al. Science 262, 2039– 2042 (1993).

    Article  CAS  Google Scholar 

  9. Kelsell, D.P. et al. Nature 387, 80–83 (1997).

    Article  CAS  Google Scholar 

  10. Estivill, X. et al. Lancet 351, 394–398 (1998).

    Article  CAS  Google Scholar 

  11. Denoyelle, F. et al. Nature 393, 319–320 (1998).

    Article  CAS  Google Scholar 

  12. Heller, S., Sheane, C.A., Javed, Z. & Hudspeth, J. Proc. Natl Acad. Sci. USA 95, 11400–11405 (1998).

    Article  CAS  Google Scholar 

  13. Kikuchi, T., Kimura, R.S., Adams, J.C. & Paul, J.C. Anat. Embryol. 191, 101–118 (1995).

    Article  CAS  Google Scholar 

  14. Van Camp, G. et al. Genomics 41, 70–74 (1997).

    Article  CAS  Google Scholar 

  15. Verselis, V.K., Ginter, C.S. & Bargiello, T.A. Nature 368, 348– 351 (1994).

    Article  CAS  Google Scholar 

  16. Suchyna, T.M. et al. Nature 365, 847–849 (1993).

    Article  CAS  Google Scholar 

  17. Deschênes, S.M. et al. J. Neurosci. 17, 9077– 9084 (1997).

    Article  Google Scholar 

  18. Bruzzone, R. et al. Neuron 13, 1253–1260 (1994).

    Article  CAS  Google Scholar 

  19. Gorlin, R.J., Toriello, H.V. & Cohen, M.M. Hereditary Hearing Loss and its Syndromes (Oxford University Press, Oxford, 1995).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. MRC Institute of Hearing Research, University of Nottingham, University Park, Nottingham, NG7 2RD, UK

    Karen P Steel

Authors
  1. Karen P Steel
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Steel, K. One connexin, two diseases. Nat Genet 20, 319–320 (1998). https://doi.org/10.1038/3781

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/3781

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing