Confirmation of oxidative stress and fatty acid disturbances in two further Papillon–Lefèvre syndrome families with identification of a new mutation

Abstract

The previously reported oxidative and fatty acids disturbances were confirmed as a feature of this condition in two further families. There are low levels of antioxidant markers and high levels of oxidative markers, in addition of low levels of some anti-inflammatory fatty acids in persons suffering PLS and some of their relatives.

One mutation, two phenotypes: a single nonsense mutation of theCTSCgene causes two clinically distinct phenotypes

“…These mutations also promote protease degradation in mature haematopoietic subsets, but do not affect protease production in progenitor cells . Biochemical analysis has demonstrated low levels of antioxidant markers and anti‐inflammatory fatty acids and high levels of oxidative markers in patients with PLS . The altered regulation of the immune response increases susceptibility to periodontal inflammation and skin infections …”

“…20 Biochemical analysis has demonstrated low levels of antioxidant markers and antiinflammatory fatty acids and high levels of oxidative markers in patients with PLS. 21 The altered regulation of the immune response increases susceptibility to periodontal inflammation and skin infections. 18,19 The p.Arg250X nonsense mutation has already been reported previously in patients with PLS, 22,23 but this is the first report of its association with HMS.…”

Therapeutic targeting of cathepsin C: from pathophysiology to treatment

“…Teeth where bone loss exceeds 30% of root length should be extracted. Unfortunately none of these measures is reliably effective (Bimstein, Lustmann, Sela, Neriah, & Soskolne, 1990;Bullon, et al, 2014;De Vree, Steenackers, & De Boever, 2000;Glenwright & Rock, 1990;Hathway, 1982;Hattab, Rawashdeh, Yassin, al-Momani, & al-Ubosi, 1995;Rateitschak-Pluss & Schroeder, 1984).…”

Autophagic dysfunction in patients with Papillon-Lefèvre syndrome is restored by recombinant cathepsin C treatment

“…Thus many patients with PLS show increased susceptibility to infections and periodontal disease. 2 Given that autophagy plays a key role in the defense mechanism against bacterial infections and autophagic dysfunction has been associated with inflammation and infection progression, 7 our data could help to better understand this susceptibility. Autophagy is also involved Data represent mean -SDs of 3 separate experiments.…”

“…Patient 3 was a 41-year-old woman harboring a previously described mutation (homozygote for a point deletion, c1140delC, corresponding to amino acid position p.S381TTKRGSTTTLV* and resulting in a premature stop codon, see the Methods section in this article's Online Repository). 2 The patient presented with hyperkeratosis in the palmoplantar region of the elbows and hands and had severe periodontitis that led to edentulism. The human CatC sequence is processed into a mature form and produces a trimer consisting of the exclusion domain, heavy chain, and light chain, which are bound by disulfide bonds.…”