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

TY - JOUR

T1 - Cloning of multiple keratin 16 genes facilitates prenatal diagnosis of pachyonychia congenita type 1

AU - Smith, Frances J. D.

AU - McKusick, Victor A.

AU - Nielsen, Karl

AU - Pfendner, Ellen

AU - Uitto, Jouni

AU - McLean, W. H. Irwin

PY - 1999/10

Y1 - 1999/10

N2 - 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.

AB - 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.

U2 - 10.1002/(SICI)1097-0223(199910)19:10<941::AID-PD663>3.0.CO;2-W

DO - 10.1002/(SICI)1097-0223(199910)19:10<941::AID-PD663>3.0.CO;2-W

M3 - Article

SN - 0197-3851

VL - 19

SP - 941

EP - 946

JO - Prenatal Diagnosis

JF - Prenatal Diagnosis

IS - 10

ER -