title: Cathepsin C gene 5'-untranslated region mutation in papillon-lefèvre syndrome.
abstract: BACKGROUND
  Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder characterized by palmoplantar keratoderma together with a severe form of generalized aggressive periodontitis and associated with mutations in cathepsin C gene (CTSC).
  
  
  OBJECTIVE
  To investigate the clinical and mutational characteristics of 6 PLS patients from 4 unrelated Slovenian families.
  
  
  METHODS
  CTSC mutational and functional analyses were performed.
  
  
  RESULTS
  In all patients, a novel homozygous substitution, c.-55C>A, in the CTSC 5'-untranslated region (UTR) was detected on genomic DNA level and confirmed by mRNA analysis, resulting in the almost complete loss of CTSC mRNA expression and CTSC activity. In silico analysis revealed the potential of the mutation to disrupt putative transcription factor binding sites (TFBSs) for AP-2 and Sp families of transcription factors.
  
  
  CONCLUSIONS
  Identification of a novel CTSC 5'-UTR mutation together with a severe reduction of CTSC mRNA expression and virtually nonexistent CTSC activity was suggestive of a novel mechanism of TFBS dysfunction associated with PLS.
authors.affiliation: Department of Paediatric and Preventive Dentistry, University Children’s Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.
authors.forename: Rok
authors.initials: R
authors.lastname: Kosem
authors.forename: Maruša
authors.initials: M
authors.lastname: Debeljak
authors.forename: Barbka
authors.initials: B
authors.lastname: Repič Lampret
authors.forename: Aleksej
authors.initials: A
authors.lastname: Kansky
authors.forename: Tadej
authors.initials: T
authors.lastname: Battelino
authors.forename: Katarina
authors.initials: K
authors.lastname: Trebušak Podkrajšek
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics*; D020789:Cathepsin C / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010214:Papillon-Lefevre Disease / Q000235:genetics*; D010375:Pedigree; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D020121:5' Untranslated Regions; D012333:RNA, Messenger; C533918:CTSC protein, human; D020789:Cathepsin C