PMID- 10581027
OWN - NLM
STAT- MEDLINE
DCOM- 19991220
LR  - 20101118
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 23
IP  - 4
DP  - 1999 Dec
TI  - Loss-of-function mutations in the cathepsin C gene result in periodontal disease 
      and palmoplantar keratosis.
PG  - 421-4
AB  - Papillon-Lefevre syndrome, or keratosis palmoplantaris with periodontopathia
      (PLS, MIM 245000), is an autosomal recessive disorder that is mainly ascertained 
      by dentists because of the severe periodontitis that afflicts patients. Both the 
      deciduous and permanent dentitions are affected, resulting in premature tooth
      loss. Palmoplantar keratosis, varying from mild psoriasiform scaly skin to overt 
      hyperkeratosis, typically develops within the first three years of life.
      Keratosis also affects other sites such as elbows and knees. Most PLS patients
      display both periodontitis and hyperkeratosis. Some patients have only
      palmoplantar keratosis or periodontitis, and in rare individuals the
      periodontitis is mild and of late onset. The PLS locus has been mapped to
      chromosome 11q14-q21 (refs 7, 8, 9). Using homozygosity mapping in eight small
      consanguineous families, we have narrowed the candidate region to a 1.2-cM
      interval between D11S4082 and D11S931. The gene (CTSC) encoding the lysosomal
      protease cathepsin C (or dipeptidyl aminopeptidase I) lies within this interval. 
      We defined the genomic structure of CTSC and found mutations in all eight
      families. In two of these families we used a functional assay to demonstrate an
      almost total loss of cathepsin C activity in PLS patients and reduced activity in
      obligate carriers.
FAU - Toomes, C
AU  - Toomes C
AD  - Department of Medical Genetics, St. Mary's Hospital, Manchester, UK.
FAU - James, J
AU  - James J
FAU - Wood, A J
AU  - Wood AJ
FAU - Wu, C L
AU  - Wu CL
FAU - McCormick, D
AU  - McCormick D
FAU - Lench, N
AU  - Lench N
FAU - Hewitt, C
AU  - Hewitt C
FAU - Moynihan, L
AU  - Moynihan L
FAU - Roberts, E
AU  - Roberts E
FAU - Woods, C G
AU  - Woods CG
FAU - Markham, A
AU  - Markham A
FAU - Wong, M
AU  - Wong M
FAU - Widmer, R
AU  - Widmer R
FAU - Ghaffar, K A
AU  - Ghaffar KA
FAU - Pemberton, M
AU  - Pemberton M
FAU - Hussein, I R
AU  - Hussein IR
FAU - Temtamy, S A
AU  - Temtamy SA
FAU - Davies, R
AU  - Davies R
FAU - Read, A P
AU  - Read AP
FAU - Sloan, P
AU  - Sloan P
FAU - Dixon, M J
AU  - Dixon MJ
FAU - Thakker, N S
AU  - Thakker NS
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (DNA Primers)
RN  - 0 (DNA, Complementary)
RN  - EC 3.4.14.1 (Cathepsin C)
SB  - IM
CIN - Nat Genet. 1999 Dec;23(4):378-80. PMID: 10581013
MH  - Aggressive Periodontitis/*enzymology/*genetics/pathology
MH  - Base Sequence
MH  - Cathepsin C/*deficiency/*genetics
MH  - Chromosomes, Human, Pair 11/genetics
MH  - DNA Primers/genetics
MH  - DNA, Complementary/genetics
MH  - Exons
MH  - Female
MH  - Genes, Recessive
MH  - Genetic Linkage
MH  - Humans
MH  - Introns
MH  - Male
MH  - Microsatellite Repeats
MH  - Papillon-Lefevre Disease/*enzymology/*genetics/pathology
MH  - Pedigree
MH  - *Point Mutation
EDAT- 1999/12/02 09:00
MHDA- 2001/03/23 10:01
CRDT- 1999/12/02 09:00
PHST- 1999/12/02 09:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/12/02 09:00 [entrez]
AID - 10.1038/70525 [doi]
PST - ppublish
SO  - Nat Genet. 1999 Dec;23(4):421-4. doi: 10.1038/70525.