PMID- 10521820
OWN - NLM
STAT- MEDLINE
DCOM- 19991208
LR  - 20091119
IS  - 0197-3851 (Print)
IS  - 0197-3851 (Linking)
VI  - 19
IP  - 10
DP  - 1999 Oct
TI  - Cloning of multiple keratin 16 genes facilitates prenatal diagnosis of
      pachyonychia congenita type 1.
PG  - 941-6
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 (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.
CI  - Copyright 1999 John Wiley & Sons, Ltd.
FAU - Smith, F J
AU  - Smith FJ
AD  - Epithelial Genetics Group, Department of Dermatology and Cutaneous Biology,
      Jefferson Medical College, 233 South 10th Street, Philadelphia, PA 19107, USA.
FAU - McKusick, V A
AU  - McKusick VA
FAU - Nielsen, K
AU  - Nielsen K
FAU - Pfendner, E
AU  - Pfendner E
FAU - Uitto, J
AU  - Uitto J
FAU - McLean, W H
AU  - McLean WH
LA  - eng
GR  - P01AR38923/AR/NIAMS NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Prenat Diagn
JT  - Prenatal diagnosis
JID - 8106540
RN  - 0 (RNA, Messenger)
RN  - 68238-35-7 (Keratins)
SB  - IM
MH  - Abnormalities, Multiple/diagnosis/*genetics
MH  - Adult
MH  - Cloning, Molecular
MH  - DNA Mutational Analysis
MH  - Ectodermal Dysplasia/diagnosis/*genetics
MH  - *Genetic Testing
MH  - Humans
MH  - Keratins/*genetics
MH  - Keratoderma, Palmoplantar/genetics
MH  - Leukoplakia, Oral/genetics
MH  - Male
MH  - Nails, Malformed/genetics
MH  - Prenatal Diagnosis/*methods
MH  - RNA, Messenger/genetics
MH  - Sequence Analysis, DNA
EDAT- 1999/10/16 00:00
MHDA- 1999/10/16 00:01
CRDT- 1999/10/16 00:00
PHST- 1999/10/16 00:00 [pubmed]
PHST- 1999/10/16 00:01 [medline]
PHST- 1999/10/16 00:00 [entrez]
AID - 10.1002/(SICI)1097-0223(199910)19:10<941::AID-PD663>3.0.CO;2-W [pii]
PST - ppublish
SO  - Prenat Diagn. 1999 Oct;19(10):941-6.