Discovery - University of Dundee - Online Publications

Library & Learning Centre

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

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

Research output: Contribution to journalArticle

View graph of relations

Authors

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

Research units

Info

Original languageEnglish
Pages941-946
Number of pages6
JournalPrenatal Diagnosis
Journal publication dateOct 1999
Volume19
Issue10
DOIs
StatePublished

Abstract

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.

Documents

Library & Learning Centre

Contact | Accessibility | Policy