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Cloning of multiple keratin 16 genes facilitates prenatal diagnosis of pachyonychia congenita type 1
Author(s) -
Smith Frances J. D.,
McKusick Victor A.,
Nielsen Karl,
Pfendner Ellen,
Uitto Jouni,
McLean W. H. Irwin
Publication year - 1999
Publication title -
prenatal diagnosis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.956
H-Index - 97
eISSN - 1097-0223
pISSN - 0197-3851
DOI - 10.1002/(sici)1097-0223(199910)19:10<941::aid-pd663>3.0.co;2-w
Subject(s) - biology , genetics , pseudogene , mutation , gene , phenotype , genome
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 (ψ KRT16B and ψ 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 (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. Copyright © 1999 John Wiley & Sons, Ltd.