A spectrum of mutations in keratins K6a, K16 and K17 causing pachyonychia congenita

J Dermatol Sci. 2007 Dec;48(3):199-205. doi: 10.1016/j.jdermsci.2007.07.003. Epub 2007 Aug 24.


Background: Pachyonychia congenita (PC) is a rare autosomal dominant keratin disorder, subdivided into two major variants, PC-1 and PC-2. Predominant characteristics include hypertrophic nail dystrophy, focal palmoplantar keratoderma and oral leukokeratosis. Multiple steatocystomas that develop during puberty are a useful feature distinguishing PC-2 from PC-1. At the molecular level it has been shown that mutations in keratin K6a or K16 cause PC-1 whereas those in K6b or K17 lead to PC-2.

Objective: To identify mutations in 22 families presenting with clinical symptoms of either PC-1/focal non-epidermolytic palmoplantar keratoderma (FNEPPK) or PC-2.

Methods: Mutation analysis was performed on genomic DNA from PC patients by direct sequencing.

Results: Here, we report four new missense and five known mutations in K6a; one new deletion and three previously identified missense mutations in K16; plus one known mutation in K17.

Conclusion: With one exception, all these heterozygous mutations are within the highly conserved helix boundary motif regions at either end of the keratin rod domain. In one sporadic case, a unique mutation in K16 resulting in deletion of 24bp was found within the central rod domain, in a child with a phenotype predominantly consisting of focal plantar keratoderma. The identification of mutations in cases of PC is prerequisite for future development of gene-specific and/or mutation-specific therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Deletion
  • Heterozygote
  • Humans
  • Keratin-16 / genetics*
  • Keratin-17 / genetics*
  • Keratin-6 / genetics*
  • Mutation / genetics*
  • Mutation, Missense / genetics
  • Pachyonychia Congenita / genetics*
  • Sequence Analysis, DNA


  • KRT6A protein, human
  • Keratin-16
  • Keratin-17
  • Keratin-6