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

Prenat Diagn. 1999 Oct;19(10):941-6.


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 (psiKRT16B and psiKRT16C), 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 (388del3) 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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abnormalities, Multiple / diagnosis
  • Abnormalities, Multiple / genetics*
  • Adult
  • Cloning, Molecular
  • DNA Mutational Analysis
  • Ectodermal Dysplasia / diagnosis
  • Ectodermal Dysplasia / genetics*
  • Genetic Testing*
  • Humans
  • Keratins / genetics*
  • Keratoderma, Palmoplantar / genetics
  • Leukoplakia, Oral / genetics
  • Male
  • Nails, Malformed / genetics
  • Prenatal Diagnosis / methods*
  • RNA, Messenger / genetics
  • Sequence Analysis, DNA


  • RNA, Messenger
  • Keratins