Cloning of multiple keratin 16 genes facilitates prenatal diagnosis of pachyonychia congenita type 1

Frances J. D. Smith, Victor A. McKusick, Karl Nielsen, Ellen Pfendner, Jouni Uitto, W. H. Irwin McLean

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    Pachyonychia congenita type 1 (PC-1) is an autosomal dominant ectodermal dysplasia characterized by severe nail dystrophy, focal non-epidermolytic palmoplantar keratoderma (FNEPPK) and oral lesions. We have previously shown that mutations in keratin K16 cause fragility of specific epithelia resulting in phenotypes of PC-1 or FNEPPK alone. These earlier analyses employed an RT-PCR approach to avoid amplification of K16-like pseudogenes. Here, we have cloned the K16 gene (KRT16A) and two homologous pseudogenes (psi KRT16B and psi KRT16C), allowing development of a genomic mutation detection strategy based on a long-range PCR, which is specific for the functional K16 gene. We report a novel heterozygous 3 bp deletion mutation (388de13) in K16 in a sporadic case of PC-1. The mutation was detected in genomic DNA and confirmed at the mRNA level by RT-PCR, showing that our genomic PCR system is reliable for K16 mutation detection. Using this system, we carried out the first prenatal diagnosis for PC-1 using CVS material, correctly predicting a normal fetus. This work will greatly improve K16 mutation analysis and allow predictive testing for PC-1 and the related phenotype of FNEPPK. Copyright (C) 1999 John Wiley & Sons, Ltd.

    Original languageEnglish
    Pages (from-to)941-946
    Number of pages6
    JournalPrenatal Diagnosis
    Issue number10
    Publication statusPublished - Oct 1999

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