Keratin K6c mutations cause focal palmoplantar keratoderma

Neil J. Wilson, Andrew G. Messenger, Sancy Leachman, Edel A. O'Toole, E. Birgitte Lane, W. H Irwin McLean, Frances J D Smith

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The palmoplantar keratodermas (PPKs) are a large group of clinically and genetically heterogeneous genodermatoses. The gene defects underlying many PPKs still need to be resolved to facilitate definitive molecular diagnosis and genetic counseling. Dominant-negative mutations in any of the four identified keratin genes, KRT6A, KRT6B, KRT16, or KRT17, cause pachyonychia congenita (PC), characterized by hypertrophic nail dystrophy and other ectodermal features. In PC, focal PPK (FPPK) is the most painful and debilitating phenotypic feature. Some families presenting with FPPK alone, or with minimal nail changes, carry mutations in KRT16; however, most FPPK families do not harbor mutations in any of these keratin genes. Here, we report three unrelated families who presented with familial FPPK with minor or absent nail changes. The four PC/FPPK-related keratin genes were excluded; however, mutational analysis of the recently identified KRT6C gene, encoding keratin K6c, showed heterozygous in-frame deletion mutations in all three kindreds. Affected members of Families 1 and 2 carried the same mutation, p.Asn172del. In Family 3, the mutation p.Ile462-Glu470del co-segregated with the disease. KRT6C was shown to be expressed in the plantar epidermis using reverse transcription-PCR, consistent with the phenotype observed in this tissue. These data expand the genetic testing repertoire for the PPKs.

Original languageEnglish (US)
Pages (from-to)425-429
Number of pages5
JournalJournal of Investigative Dermatology
Volume130
Issue number2
DOIs
StatePublished - Feb 2010
Externally publishedYes

Fingerprint

Keratins
Pachyonychia Congenita
Nails
Palmoplantar Keratoderma
Genes
Mutation
Gene encoding
Transcription
Ports and harbors
Sequence Deletion
Genetic Counseling
Genetic Testing
Epidermis
Reverse Transcription
Tissue
Molecular Biology
Defects
Hyperkeratosis of the palms and soles and esophageal papillomas
Testing
Phenotype

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Wilson, N. J., Messenger, A. G., Leachman, S., O'Toole, E. A., Lane, E. B., McLean, W. H. I., & Smith, F. J. D. (2010). Keratin K6c mutations cause focal palmoplantar keratoderma. Journal of Investigative Dermatology, 130(2), 425-429. https://doi.org/10.1038/jid.2009.215

Keratin K6c mutations cause focal palmoplantar keratoderma. / Wilson, Neil J.; Messenger, Andrew G.; Leachman, Sancy; O'Toole, Edel A.; Lane, E. Birgitte; McLean, W. H Irwin; Smith, Frances J D.

In: Journal of Investigative Dermatology, Vol. 130, No. 2, 02.2010, p. 425-429.

Research output: Contribution to journalArticle

Wilson, NJ, Messenger, AG, Leachman, S, O'Toole, EA, Lane, EB, McLean, WHI & Smith, FJD 2010, 'Keratin K6c mutations cause focal palmoplantar keratoderma', Journal of Investigative Dermatology, vol. 130, no. 2, pp. 425-429. https://doi.org/10.1038/jid.2009.215
Wilson, Neil J. ; Messenger, Andrew G. ; Leachman, Sancy ; O'Toole, Edel A. ; Lane, E. Birgitte ; McLean, W. H Irwin ; Smith, Frances J D. / Keratin K6c mutations cause focal palmoplantar keratoderma. In: Journal of Investigative Dermatology. 2010 ; Vol. 130, No. 2. pp. 425-429.
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