title: Functional Cathepsin C mutations cause different Papillon-Lefèvre syndrome phenotypes.
abstract: OBJECTIVE
  The autosomal-recessive Papillon-Lefèvre syndrome (PLS) is characterized by severe aggressive periodontitis, combined with palmoplantar hyperkeratosis, and is caused by mutations in the Cathepsin C (CTSC) gene. This study aimed to identify CTSC mutations in different PLS phenotypes, including atypical forms and isolated pre-pubertal aggressive periodontitis (PAP).
  
  
  METHODS
  Thirteen families with different phenotypes were analysed by direct sequencing of the entire coding region and the regulatory regions of CTSC. The function of novel mutations was tested with enzyme activity measurements.
  
  
  RESULTS
  In 11 of 13 families, 12 different pathogenic CTSC mutations were found in 10 typical PLS patients, three atypical cases and one PAP patient. Out of four novel mutations, three result in protein truncation and are thus considered to be pathogenic. The homozygous c.854C>T nucleotide exchange (p.P285L) was associated with an almost complete loss of enzyme activity. The observed phenotypic heterogeneity could not be associated with specific genotypes.
  
  
  CONCLUSIONS
  The phenotypic variability of the PLS associated with an identical genetic background may reflect the influence of additional genetic or environmental factors on disease characteristics. CTSC mutation analyses should be considered for differential diagnosis in all children suffering from severe aggressive periodontitis.
authors.affiliation: Department of Conservative Dentistry, University Hospital Carl Gustav Carus, TU Dresden, Germany. Barbara.Noack@uniklinikum-dresden.de
authors.forename: Barbara
authors.initials: B
authors.lastname: Noack
authors.forename: Heike
authors.initials: H
authors.lastname: Görgens
authors.forename: Beate
authors.initials: B
authors.lastname: Schacher
authors.forename: Magda
authors.initials: M
authors.lastname: Puklo
authors.forename: Peter
authors.initials: P
authors.lastname: Eickholz
authors.forename: Thomas
authors.initials: T
authors.lastname: Hoffmann
authors.forename: Hans Konrad
authors.initials: HK
authors.lastname: Schackert
mesh_terms: D000328:Adult; D010520:Aggressive Periodontitis / Q000201:enzymology* / Q000235:genetics*; D020789:Cathepsin C / Q000235:genetics*; D002648:Child; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D016368:Frameshift Mutation; D006801:Humans; D019272:Leukocyte Elastase / Q000235:genetics; D020125:Mutation, Missense; D010214:Papillon-Lefevre Disease / Q000201:enzymology* / Q000235:genetics*; D010641:Phenotype
chemical_list: D018389:Codon, Nonsense; D020789:Cathepsin C; D019272:Leukocyte Elastase