A large mutational study in pachyonychia congenita

Neil J. Wilson, Sancy Leachman, C. David Hansen, Alexandra C. McMullan, Leonard M. Milstone, Mary E. Schwartz, W. H Irwin McLean, Peter R. Hull, Frances J D Smith

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Pachyonychia congenita (PC) is a rare autosomal dominant skin disorder characterized predominantly by nail dystrophy and painful palmoplantar keratoderma. Additional clinical features include oral leukokeratosis, follicular keratosis, and cysts (steatocysts and pilosebaceous cysts). PC is due to heterozygous mutations in one of four keratin genes, namely, KRT6A, KRT6B, KRT16, or KRT17. Here, we report genetic analysis of 90 new families with PC in which we identified mutations in KRT6A, KRT6B, KRT16, or KRT17, thereby confirming their clinical diagnosis. A total of 21 previously unreported and 22 known mutations were found. Approximately half of the kindreds had mutations in KRT6A (52%), 28% had mutations in KRT16, 17% in KRT17, and 3% of families had mutations in KRT6B. Most of the mutations were heterozygous missense or small in-frame insertion/deletion mutations occurring within one of the helix boundary motif regions of the keratin polypeptide. More unusual mutations included heterozygous splice site mutations, nonsense mutations, and a 1-bp insertion mutation, leading to a frameshift and premature termination codon. This study, together with previously reported mutations, identifies mutation hotspot codons that may be useful in the development of personalized medicine for PC.

Original languageEnglish (US)
Pages (from-to)1018-1024
Number of pages7
JournalJournal of Investigative Dermatology
Volume131
Issue number5
DOIs
StatePublished - May 2011
Externally publishedYes

Fingerprint

Pachyonychia Congenita
Keratins
Nails
Mutation
Medicine
Skin
Genes
Peptides
Nonsense Codon
INDEL Mutation
Follicular Cyst
Palmoplantar Keratoderma
Oral Leukoplakia
Keratosis
Precision Medicine
Insertional Mutagenesis
Codon

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Wilson, N. J., Leachman, S., Hansen, C. D., McMullan, A. C., Milstone, L. M., Schwartz, M. E., ... Smith, F. J. D. (2011). A large mutational study in pachyonychia congenita. Journal of Investigative Dermatology, 131(5), 1018-1024. https://doi.org/10.1038/jid.2011.20

A large mutational study in pachyonychia congenita. / Wilson, Neil J.; Leachman, Sancy; Hansen, C. David; McMullan, Alexandra C.; Milstone, Leonard M.; Schwartz, Mary E.; McLean, W. H Irwin; Hull, Peter R.; Smith, Frances J D.

In: Journal of Investigative Dermatology, Vol. 131, No. 5, 05.2011, p. 1018-1024.

Research output: Contribution to journalArticle

Wilson, NJ, Leachman, S, Hansen, CD, McMullan, AC, Milstone, LM, Schwartz, ME, McLean, WHI, Hull, PR & Smith, FJD 2011, 'A large mutational study in pachyonychia congenita', Journal of Investigative Dermatology, vol. 131, no. 5, pp. 1018-1024. https://doi.org/10.1038/jid.2011.20
Wilson NJ, Leachman S, Hansen CD, McMullan AC, Milstone LM, Schwartz ME et al. A large mutational study in pachyonychia congenita. Journal of Investigative Dermatology. 2011 May;131(5):1018-1024. https://doi.org/10.1038/jid.2011.20
Wilson, Neil J. ; Leachman, Sancy ; Hansen, C. David ; McMullan, Alexandra C. ; Milstone, Leonard M. ; Schwartz, Mary E. ; McLean, W. H Irwin ; Hull, Peter R. ; Smith, Frances J D. / A large mutational study in pachyonychia congenita. In: Journal of Investigative Dermatology. 2011 ; Vol. 131, No. 5. pp. 1018-1024.
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