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

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 (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.

• Authors: F J Smith, V A McKusick, K Nielsen, E Pfendner, J Uitto, W H McLean
• Journal: Prenatal diagnosis (Prenat Diagn) Vol. 19 Issue 10 Pg. 941-6 (Oct 1999) ISSN: 0197-3851 [Print] England
• PMID: 10521820 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 1999 John Wiley & Sons, Ltd.

Chemical References

• RNA, Messenger
• Keratins

Topics

• Abnormalities, Multiple (diagnosis, genetics)
• Adult
• Cloning, Molecular
• DNA Mutational Analysis
• Ectodermal Dysplasia (diagnosis, 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