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

Haihui Liao, Jane M. Sayers, Neil J. Wilson, Alan D. Irvine, Jemima E. Mellerio, Eulalia Baselga, Susan J. Bayliss, Vera Uliana, Michele Fimiani, E. Birgitte Lane, W. H. Irwin McLean, Sancy A. Leachman, Frances J. D. Smith

    Research output: Contribution to journalArticlepeer-review

    47 Citations (Scopus)

    Abstract

    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 24 bp 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. © 2007 Japanese Society for Investigative Dermatology.
    Original languageEnglish
    Pages (from-to)199-205
    Number of pages7
    JournalJournal of Dermatological Science
    Volume48
    Issue number3
    DOIs
    Publication statusPublished - Dec 2007

    Keywords

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

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