The genetic basis of pachyonychia congenita.

Frances J.D. Smith, Haihui Liao, Andrew J. Cassidy, Arlene Stewart, Kevin J. Hamill, Pamela Wood, Iris Joval, Maurice A.M. van Steensel, Erik Björck, Faith Callif-Daley, Gerald Pals, Paul Collins, Sancy A. Leachman, Colin S. Munro, W. H.Irwin McLean

Research output: Contribution to journalArticlepeer-review

88 Scopus citations


In 1994, the molecular basis of pachyonychia congenita (PC) was elucidated. Four keratin genes are associated with the major subtypes of PC: K6a or K16 defects cause PC-1; and mutations in K6b or K17 cause PC-2. Mutations in keratins, the epithelial-specific intermediate filament proteins, result in aberrant cytoskeletal networks which present clinically as a variety of epithelial fragility phenotypes. To date, mutations in 20 keratin genes are associated with human disorders. Here, we review the genetic basis of PC and report 30 new PC mutations. Of these, 25 mutations were found in PC-1 families and five mutations were identified in PC-2 kindreds. All mutations identified were heterozygous amino acid substitutions or small in-frame deletion mutations with the exception of an unusual mutation in a sporadic case of PC-1. The latter carried a 117 bp duplication resulting in a 39 amino acid insertion in the 2B domain of K6a. Also of note was mutation L388P in K17, which is the first genetic defect identified in the helix termination motif of this protein. Understanding the genetic basis of these disorders allows better counseling for patients and paves the way for therapy development.

Original languageEnglish (US)
Pages (from-to)21-30
Number of pages10
JournalThe journal of investigative dermatology. Symposium proceedings / the Society for Investigative Dermatology, Inc. [and] European Society for Dermatological Research
Issue number1
StatePublished - Oct 2005
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Biology
  • Dermatology
  • Cell Biology


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