Papillon–Lefèvre syndrome: report of six patients and identification of a novel mutation

Abstract

Papillon-Lefèvre syndrome is an autosomal recessive genodermatosis typically manifesting with the constellation of palmoplantar keratoderma and progressive early-onset periodontitis. The cutaneous phenotype can be strikingly psoriasiform, possibly posing a diagnostic challenge. This rare disorder is caused by loss-of-function mutations in the CTSC gene, which encodes cathepsin C. We report six patients with Papillon-Lefèvre syndrome from five consanguineous Turkish families, in whom genetic analysis of the CTSC gene revealed four recurrent mutations (c.415G>A; c.1015C>T; c.1019A>G; and c.103-105delCTG) and a novel missense mutation (c.117G>T) in the homozygous state.

Papillon-Lefévre syndrome: Case report and genetic analysis

“…Mutation of c.415 G>A, seen in this presented case was defined first by Zhang et al as heterozygous in a PLS patient with Caucasian origin 13 . Cases carrying homozygous c.415 G>A mutation have also been reported 17,18 . CTSC, CTSG and elastase functions are almost completely lost in homozygous mutations 17 .…”

Environmental lead effects on gene expression in oral epithelial cells

“…cathepsin C (CTSC) is a critical coordinating point for activation of many serine proteinases, eg, elastase, cathepsin G and granzymes A and B, in immune cells. Mutations in CTSC have been demonstrated to cause Papillon‐Lefèvre syndrome, as well as having a role in prepubertal and aggressive periodontitis potentially interfaced with the activities of proteinase 3 in the generation of antimicrobial peptides . Amyloid beta precursor protein is a cell surface receptor that is cleaved by secretases and can promote transcription activation and inhibit Notch signaling, linked with apoptosis‐inducing pathways.…”

Missing in action—The meaning of cell death in tissue damage and inflammation

“…In PLS, NET‐formation is compromised by a mutated Cathepsin C that renders all neutrophil serine proteases inactive and therefore impedes chromatin decondensation and canonical NET formation . Subjects with PLS are characterized by hyperactivation of neutrophils resulting in exaggerated and non‐resolving inflammation, especially in the oral cavity and the skin . Interestingly, in experimental lupus and gouty arthritis neutrophil depletion or neutropenia worsens disease .…”