title: Identification of cathepsin C mutations in ethnically diverse papillon-Lefèvre syndrome patients.
abstract: BACKGROUND
  Papillon-Lefèvre syndrome (PLS) is an autosomal recessive disorder characterised by palmoplantar keratoderma and severe, early onset periodontitis, which results from deficiency of cathepsin C activity secondary to mutations in the cathepsin C gene. To date, 13 different cathepsin C mutations have been reported in PLS patients, all of which are homozygous for a given mutation, reflecting consanguinity.
  
  
  OBJECTIVE
  To evaluate the generality of cathepsin C mutations in PLS, we studied an ethnically diverse group of 20 unrelated families.
  
  
  METHODS
  Mutations were identified by direct automated sequencing of genomic DNA amplified for exonic regions and associated splice site junctions of the cathepsin C gene. Long range PCR was performed to determine the genomic structure of the cathepsin C gene.
  
  
  RESULTS
  The cathepsin C gene spans over 46 kb, with six introns ranging in size from 1.6 to 22.4 kb. Eleven novel mutations and four previously reported mutations were identified in affected subjects from 14 families. Missense mutations were most common (9/15), followed by nonsense mutations (3/15), insertions (2/15), and deletions (1/15). Among these 14 probands, two were compound heterozygotes. Affected subjects with transgressions of the dermal lesions onto the knees or elbows or both had mutations in both the pro- and mature regions of the enzyme, although most were in the mature region.
  
  
  CONCLUSIONS
  Mutations in the mature region of cathepsin C were more likely to be associated with the transgressions of the dermatological lesions, although the results were not statistically significant. A comprehensive list of all cathepsin C mutations described to date, representing 25 mutations from 32 families with PLS and related conditions, is also presented.
authors: University of Pittsburgh, Department of Human Genetics, Pittsburgh, PA 15261, USA. hart@cpc.pitt.edu
authors: P S
authors: PS
authors: Hart
authors: Y
authors: Y
authors: Zhang
authors: E
authors: E
authors: Firatli
authors: C
authors: C
authors: Uygur
authors: M
authors: M
authors: Lotfazar
authors: M D
authors: MD
authors: Michalec
authors: J J
authors: JJ
authors: Marks
authors: X
authors: X
authors: Lu
authors: B J
authors: BJ
authors: Coates
authors: W K
authors: WK
authors: Seow
authors: R
authors: R
authors: Marshall
authors: D
authors: D
authors: Williams
authors: J B
authors: JB
authors: Reed
authors: J T
authors: JT
authors: Wright
authors: T C
authors: TC
authors: Hart
mesh_terms: D020789:Cathepsin C / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010214:Papillon-Lefevre Disease / Q000201:enzymology / Q000208:ethnology* / Q000235:genetics*; D010518:Periodontitis / Q000201:enzymology / Q000208:ethnology* / Q000235:genetics*; D013577:Syndrome
chemical_list: D020789:Cathepsin C