Genotype-phenotype correlations among pachyonychia congenita patients with K16 mutations

Teresa Fu, Sancy Leachman, Neil J. Wilson, Frances J D Smith, Mary E. Schwartz, Jean Y. Tang

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Pachyonychia congenita (PC) is a rare, autosomal dominant keratin disorder caused by mutations in four genes (KRT6A, KRT6B, KRT16, or KRT17). The International PC Research Registry is a database with information on patients symptoms as well as genotypes. We sought to describe the heterogeneity of clinical symptoms and to investigate possible genotype-phenotype correlations in patients with two types of K16 mutations, p.Asn125 and p.Arg127, causing the PC-16 subtype of PC. We found that clinical symptoms depended on the type of amino-acid substitution. Patients with p.Asn125Asp and p.Arg127Pro mutations exhibited more severe disease than patients carrying p.Asn125Ser and p.Arg127Cys mutations in terms of age of onset of symptoms, extent of nail involvement, and impact on daily quality of life. We speculate that amino-acid substitutions causing larger, more disruptive changes to the K16 protein structure, such as a change in amino-acid charge in the p.Asn125Asp mutation or a bulky proline substitution in the p.Arg127Pro mutation, may also lead to more severe disease phenotypes. The variation in phenotypes seen with different substitutions at the same mutation site suggests a genotype-phenotype correlation. Knowledge of the exact gene defect is likely to assist in predicting disease prognosis and clinical management.

Original languageEnglish (US)
Pages (from-to)1025-1028
Number of pages4
JournalJournal of Investigative Dermatology
Volume131
Issue number5
DOIs
StatePublished - May 2011

Fingerprint

Pachyonychia Congenita
Genetic Association Studies
Substitution reactions
Mutation
Amino Acids
Genes
Nails
Amino Acid Substitution
Keratins
Proline
Phenotype
Defects
Age of Onset
Registries
Genotype
Quality of Life
Databases
Proteins

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Genotype-phenotype correlations among pachyonychia congenita patients with K16 mutations. / Fu, Teresa; Leachman, Sancy; Wilson, Neil J.; Smith, Frances J D; Schwartz, Mary E.; Tang, Jean Y.

In: Journal of Investigative Dermatology, Vol. 131, No. 5, 05.2011, p. 1025-1028.

Research output: Contribution to journalArticle

Fu, Teresa ; Leachman, Sancy ; Wilson, Neil J. ; Smith, Frances J D ; Schwartz, Mary E. ; Tang, Jean Y. / Genotype-phenotype correlations among pachyonychia congenita patients with K16 mutations. In: Journal of Investigative Dermatology. 2011 ; Vol. 131, No. 5. pp. 1025-1028.
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