Skip to main content

Thank you for visiting 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.

Mutation of a type II keratin gene (K6a) in pachyonychia congenita


Pachyonychia congenita (PC) is a rare autosomal dominant condition characterized by multiple ectodermal abnormalities1–3. Patients with Jadassohn-Lewandowsky Syndrome (MIM ♯167200; PC-1) have nail defects (onchyogryposis), palmoplantar hyperkeratosis, follicular hyperkeratosis and oral leukokeratosis4. Those with the rarer Jackson-Lawler Syndrome (MIM ♯167210; PC-2) lack oral involvement but have natal teeth and cutaneous cysts5. Ultra-structural studies have identified abnormal keratin tonofilaments6 and linkage to the keratin gene cluster on chromosome 17 has been found in PC families7. Keratins are the major structural proteins of the epidermis and associated appendages and the nail, hair follicle, palm, sole and tongue are the main sites of constitutive K6, K16 and K17 expression8–10. Furthermore, mutations in K16 and K17 have recently been identified in some PC patients11. Although we did not detect K16 or K17 mutations in PC families from Slovenia, we have found a heterozygous deletion in a K6 isoform (K6a) in the affected members of one family. This 3 bp deletion (AAC) in exon 1 of K6a removes a highly conserved asparagine residue (ΔN170) from position 8 of the 1A helical domain (ΔN8). This is the first K6a mutation to be described and this heterozygous K6a deletion is sufficient to explain the pathology observed in this PC-1 family.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. Kansky, A., Penko, M. & Milakic-Snoj, Z. Pachyonychia congenita. Acta Dermatovener. APA 3, 153–160 (1994).

    Google Scholar 

  2. Feinstein, A., Friedman, J. & Schewach-Millet, M. Pachyonychia congenita. J. Am. Acad. Dermatol. 19 (4), 705–711 (1988).

    CAS  Article  Google Scholar 

  3. McKusick, V.A. Mendelian Inheritance in Man, 11th Edition. 1086 (The John Hopkins University Press, Baltimore, 1994).

    Google Scholar 

  4. Thormann, J. & Kobayasi, T. Pachyonychia congenita Jadassohn-Lewandowsky: A disorder of keratinization. Acta Dermat. 57, 63–67 (1977).

    CAS  Google Scholar 

  5. Clementi, M., Cardin de Stephani, E., Dei-Rossi, C. & Tenconi, R. Pachyonychia congenita Jackson-Lawler type: a distinct malformation syndrome. Brit. J. Dermatol. 114, 367–370 (1986).

    CAS  Article  Google Scholar 

  6. Thomas, D.R. et al. Pachyonychia congenita — Electron microscopic and epidermal glycoprotein assessment before and during isotretinoin treatment. Arch. Dermatol. 120, 1475–1479 (1984).

    CAS  Article  Google Scholar 

  7. Munro, C.S. et al. A gene for pachyonychia congenita is closely linked to the keratin gene cluster on 17q12–q21. J. med. Genet. 31, 675–678 (1994).

    CAS  Article  Google Scholar 

  8. Bowden, P.E., Stark, H.-J., Breitkreutz, D. & Fusenig, N.E. Expression and modification of keratins during terminal differentiation of mammalian epidermis. in Current Topics in Developmental Biology: The Molecular and Developmental Biology of Keratins. 35–68 (Academic Press, Orlando, 1987).

    Chapter  Google Scholar 

  9. Stark, H.-J. et al. Keratins of the human hair follicle. “Hyperproliferative” keratins consistently expressed in outer root sheath cells in vivo and in vitro. Differentiation. 35, 236–248 (1987).

    CAS  Article  Google Scholar 

  10. Lindberg, K. & Rheinwald, J.G. Three distinct keratinocyte subtypes identified in human oral epithelium by their patterns of keratin expression in culture and in xenografts. Differentiation 45, 230–241 (1990).

    CAS  Article  Google Scholar 

  11. McLean, W.H. et al. Keratin 16 and keratin 17 mutations cause pachyonychia congenita. Nature Genet. 9, 273–278 (1995).

    CAS  Article  Google Scholar 

  12. Rothnagel, J.A. & Roop, D.R. Molecular genetics of keratin disorders: Analysis and diagnosis. Curr. Opin. Dermatol. 2, 211–216 (1994).

    Google Scholar 

  13. Bonifas, J.M., Rothman, A.L. & Epstein, E.H. Epidermolysis bullosa simplex: evidence in two families for keratin gene abnormalities. Science 254, 1202–1205 (1991).

    CAS  Article  Google Scholar 

  14. Rothnagel, J.A. et al. Mutations in the rod domains of keratins 1 and 10 in epidermolytic hyperkeratosis. Science. 257, 1128–1130 (1992).

    CAS  Article  Google Scholar 

  15. Rothnagel, J.A. et al. Mutations in the rod domain of keratin 2e in patients with ichthyosis bullosa of Siemens. Nature Genet. 7, 485–9 (1994).

    CAS  Article  Google Scholar 

  16. Reis, A. et al. Keratin 9 gene mutations in epidermolytic palmoplantar keratoderma (EPPK). Nature Genet. 6, 174–179 (1994).

    CAS  Article  Google Scholar 

  17. Haber, R.M. & Rose, T.H. Autosomal recessive Pachyonychia congenita. Arch. Dermatol. 122, 919–923 (1986).

    CAS  Article  Google Scholar 

  18. Franzot, J., Kansky, A. & Kavcic, S. Pachyonychia congenita (Jadasson-Lewandowsky syndrome). A review of 14 cases in Slovenia. Dermatologica 162, 462–472 (1981).

    CAS  Article  Google Scholar 

  19. Kansky, A. & Basta-Juzbasic, A. Pachyonychia congenita (Jadasson-Lewandowsky syndrome). Evaluation of symptoms in 36 patients. Arch. Dermatol. Res. 285, 36–37 (1993).

    CAS  Article  Google Scholar 

  20. Bowden, P.E. Keratins and other epidermal proteins. in Molecular Aspects of Dermatology.(ed. Priestly, G.C.) 19–54 (John Wiley & Sons, New York, 1993).

    Google Scholar 

  21. Steinert, P.M. & Roop, D.R. Molecular and cellular biology of intermediate filaments. A. Rev. Biochem. 57, 593–625 (1988).

    CAS  Article  Google Scholar 

  22. Moll, R., Franke, W.W., Schiller, D.L., Geiger, B. & Krepler, R. The catalog of human cytokeratins: patterns of expression in normal epithelia, tumours, and cultured cells. Cell 31, 11–24 (1982).

    CAS  Article  Google Scholar 

  23. Bowden, P.E., Wood, E.J. & Cunliffe, W.J. Comparison of prekeratin and keratin polypeptides in normal and psoriatic human epidermis. Biochem. Biophys. Acta. 743, 172–179 (1983).

    CAS  PubMed  Google Scholar 

  24. Yoon, S.-J., LeBlanc-Straceski, J., Ward, D., Krauter, K. & Kucherlapati, R. Organization of the human keratin type II gene cluster at 12q13. Genomics 24, 502–508 (1994).

    CAS  Article  Google Scholar 

  25. Rosenberg, M., RayChaudhury, A., Shows, T.B., LeBeau, M.M. & Fuchs, E. A group of type I keratin genes on human chromosome 17: characterization and expression Molec. cell. Biol. 8, 722–736 (1988).

    CAS  Article  Google Scholar 

  26. Chen, M.A., Bonifas, J.M., Matsumura, K., Blumenfeld, A & Epstein, E.H. A novel three-nucleotide deletion in the helix 2B region of keratin 14 in epidermolysis bullosa simplex: ΔE375. Hum. molec. Genet. 2, 1971–1972 (1993).

    CAS  Article  Google Scholar 

  27. Tyner, A.L., Eichman, M.J. & Fuchs, E. The sequence of a type II keratin gene expressed in human skin: Conservation of structure among all intermediate filament genes. Proc. Natl. Acad. Sci. U.S.A. 82, 4683–4687 (1985).

    CAS  Article  Google Scholar 

  28. Hanukoglu, I. & Fuchs, E. The cDNA sequence of a type II cytoskeletal keratin reveals constant and variable structural domains amongst keratins. Cell 33, 915–924 (1983).

    CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations


Rights and permissions

Reprints and Permissions

About this article

Cite this article

Bowden, P., Haley, J., Kansky, A. et al. Mutation of a type II keratin gene (K6a) in pachyonychia congenita. Nat Genet 10, 363–365 (1995).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

Further reading


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