title: Evidence for a founder mutation in the cathepsin C gene in three families with Papillon-Lefèvre syndrome.
abstract: BACKGROUND
  Papillon-Lefèvre syndrome (PLS; OMIM 245000) is a rare autosomal recessive disorder. Clinically, PLS is characterized by hyperkeratosis involving the palms, soles, elbows and knees which is followed later on by periodontitis, destruction of alveolar bone and loss of primary and permanent teeth. The condition is caused by mutations in the cathepsin C (CTSC) gene.
  
  
  METHODS
  We analyzed the DNA of members from 3 consanguineous families for mutations in the CTSC gene by direct sequencing analysis. We then performed haplotype analysis.
  
  
  RESULTS
  We identified an identical recurrent missense mutation, R272P, in all 3 families. Microsatellite marker analysis around the CTSC gene revealed the same haplotype on the mutation-carrying allele in all 3 families.
  
  
  CONCLUSIONS
  The presence of this common mutation in families from 2 different geographical areas provides evidence for a founder effect for CTSC mutations in PLS.
authors.affiliation: Department of Dermatology, Columbia University, New York, N.Y., USA.
authors.forename: Mazen
authors.initials: M
authors.lastname: Kurban
authors.forename: Muhammad
authors.initials: M
authors.lastname: Wajid
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shimomura
authors.forename: Ruba
authors.initials: R
authors.lastname: Bahhady
authors.forename: Abdul-Ghani
authors.initials: AG
authors.lastname: Kibbi
authors.forename: Angela M
authors.initials: AM
authors.lastname: Christiano
mesh_terms: D020789:Cathepsin C / Q000097:blood / Q000235:genetics*; D003241:Consanguinity; D004550:Elbow / Q000473:pathology; D005190:Family; D018703:Founder Effect; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007645:Keratoderma, Palmoplantar / Q000235:genetics; D007717:Knee / Q000473:pathology; D007861:Lebanon; D018895:Microsatellite Repeats; D020125:Mutation, Missense; D010154:Pakistan; D010214:Papillon-Lefevre Disease / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010518:Periodontitis / Q000235:genetics
chemical_list: D005819:Genetic Markers; D020789:Cathepsin C