Avtor/Urednik		Kosem, Rok; Debeljak, Maruša; Repič-Lampret, Barbka; Kansky, Aleksej; Battelino, Tadej; Trebušak Podkrajšek, Katarina
Naslov		Cathepsin C Gene 5'-Untranslated Region Mutation in Papillon-Lefèvre Syndrome
Tip		članek
Vol. in št.		Letnik 225, št. 3
Leto izdaje		2012
Obseg		str. 193-203
ISSN		1018-8665 - Dermatology (Basel, Switzerland)
Jezik		eng
Abstrakt		Background: Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder characterized by palmoplantar keratoderma together with a severe formof generalized aggressive periodontitis and associated with mutations in cathepsin C gene (CTSC). Objective: To investigate the clinical and mutationalcharacteristics 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 5Ž-untranslated region (UTR) was detected on genomic DNA level and confirmed by mRNA analysis, resulting in the almost complete loss of CTSC mRNAexpression and CTSC activity. In silico analysis revealed the potential ofthe mutation to disrupt putative transcription factor binding sites (TFBSs) for AP-2 and Sp families of transcription factors. Conclusion: Identification of a novel CTSC 5Ž-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.
Proste vsebinske oznake		aggressive periodontitis cathepsin C mutation detection palmoplantar keratoderma Papillon-Lefèvre syndrome