Genotype-phenotype correlations among pachyonychia congenita patients with K16 mutations

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

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    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
    Pages (from-to)1025-1028
    Number of pages4
    JournalJournal of Investigative Dermatology
    Volume131
    Issue number5
    DOIs
    Publication statusPublished - May 2011

    Cite this

    Fu, T., Leachman, S. A., Wilson, N. J., Smith, F. J. D., Schwartz, M. E., & Tang, J. Y. (2011). Genotype-phenotype correlations among pachyonychia congenita patients with K16 mutations. Journal of Investigative Dermatology, 131(5), 1025-1028. https://doi.org/10.1038/jid.2010.373