PMID- 10232400
OWN - NLM
STAT- MEDLINE
DCOM- 19990622
LR  - 20191103
IS  - 0906-6705 (Print)
IS  - 0906-6705 (Linking)
VI  - 8
IP  - 2
DP  - 1999 Apr
TI  - A mutation detection strategy for the human keratin 6A gene and novel missense
      mutations in two cases of pachyonychia congenita type 1.
PG  - 109-14
AB  - Pachyonychia congenita type 1 (PC-1) is an autosomal dominant ectodermal
      dysplasia characterized by hypertrophic nail dystrophy, focal non-epidermolytic
      palmoplantar keratoderma and variable features of oral leukokeratosis and
      follicular keratosis. Previously, we have shown that this disease can be caused
      by mutations in type I keratin K16 and one mutation has been reported in its type
      II keratin expression partner, K6a. Mutation analysis for K6a has been hampered
      by the presence of multiple copies of the K6 gene in the human genome, of which
      some are expressed and others are pseudogenes. Here, we describe a mutation
      detection strategy where the entire KRT6A gene, approximately 7 kb, is
      specifically amplified by long-range PCR. Using this technique, we have detected 
      two novel mutations in the 1A domain of the K6a polypeptide, N171K and F174S.
      Mutations were confirmed in the affected individuals and were excluded from 50
      unaffected unrelated individuals by restriction enzyme analysis of KRT6A PCR
      products. Additionally, mutation N171K was confirmed by RT-PCR in mRNA derived
      from lesional palmoplantar epidermis of an affected individual, confirming the
      specificity of the genomic PCR for the functional K6a gene. This, together with a
      similar strategy which we have developed for the K16 gene, provide a robust
      system for mutation detection and prenatal diagnosis for patients with PC-1.
FAU - Smith, F J
AU  - Smith FJ
AD  - Department of Dermatology and Cutaneous Biology, Jefferson Medical College,
      Philadelphia, PA 19107, USA.
FAU - McKenna, K E
AU  - McKenna KE
FAU - Irvine, A D
AU  - Irvine AD
FAU - Bingham, E A
AU  - Bingham EA
FAU - Coleman, C M
AU  - Coleman CM
FAU - Uitto, J
AU  - Uitto J
FAU - McLean, W H
AU  - McLean WH
LA  - eng
GR  - P01-AR38923/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  - Denmark
TA  - Exp Dermatol
JT  - Experimental dermatology
JID - 9301549
RN  - 68238-35-7 (Keratins)
SB  - IM
MH  - Amino Acid Substitution
MH  - Base Sequence
MH  - Ectodermal Dysplasia/*genetics
MH  - Exons
MH  - Female
MH  - Genome, Human
MH  - Humans
MH  - Keratins/*genetics
MH  - Male
MH  - Multigene Family
MH  - *Mutation, Missense
MH  - Nails, Malformed/*genetics
MH  - Pedigree
MH  - Skin Diseases/*genetics
EDAT- 1999/05/08 00:00
MHDA- 1999/05/08 00:01
CRDT- 1999/05/08 00:00
PHST- 1999/05/08 00:00 [pubmed]
PHST- 1999/05/08 00:01 [medline]
PHST- 1999/05/08 00:00 [entrez]
AID - 10.1111/j.1600-0625.1999.tb00356.x [doi]
PST - ppublish
SO  - Exp Dermatol. 1999 Apr;8(2):109-14. doi: 10.1111/j.1600-0625.1999.tb00356.x.