Analysis of urinary cathepsin C for diagnosing Papillon-Lefèvre syndrome

Yveline Hamon, Monika Legowska, Patricia Fergelot, Sandrine Dallet-Choisy, Louise Newell, Lise Vanderlynden, Ali Kord Valeshabad, Karina Acrich, Hadi Kord, Tsamakis Charalampos, Fanny Morice-Picard, Ian Surplice, Jerome Zoidakis, Karen David, Antonia Vlahou, Shivanna Ragunatha, Nikoletta Nagy, Katalin Farkas, Márta Széll, Cyril GoizetBeate Schacher, Maurizio Battino, Abdullah Al Farraj Aldosari, Xinwen Wang, Yang Liu, Sylvain Marchand-Adam, Adam Lesner, Elodie Kara, Sevil Korkmaz-Icöz, Celia Moss, Peter Eickholz, Alain Taieb, Salih Kavukcu, Dieter E. Jenne, Francis Gauthier, Brice Korkmaz

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5 Citations (Scopus)

Abstract

Papillon-Lefèvre syndrome (PLS) (OMIM: 245000) is a rare disease characterized by severe periodontitis and palmoplantar keratoderma. It is caused by mutations in both alleles of the cathepsin C (CatC) gene CTSC that completely abrogate the proteolytic activity of this cysteine proteinase. Most often, a genetic analysis to enable early and rapid diagnosis of PLS is unaffordable or unavailable. In this study, we tested the hypothesis that active CatC is constitutively excreted and can be easily traced in the urine of normal subjects. If this is true, determining its absence in the urine of patients would be an early, simple, reliable, low-cost and easy diagnostic technique. All 75 urine samples from healthy control subjects (aged 3 months to 80 years) contained proteolytically active CatC and its proform, as revealed by kinetic analysis and immunochemical detection. Of the urine samples of 31 patients with a PLS phenotype, 29 contained neither proteolytically active CatC nor the CatC antigen, so that the PLS diagnosis was confirmed. CatC was detected in the urine of the other two patients, and genetic analysis revealed no loss-of-function mutation in CTSC, indicating that they suffer from a PLS-like condition but not from PLS. Screening for the absence of urinary CatC activity soon after birth and early treatment before the onset of PLS manifestations will help to prevent aggressive periodontitis and loss of many teeth, and should considerably improve the quality of life of PLS patients.

Original languageEnglish
Pages (from-to)498-509
Number of pages12
JournalFEBS Journal
Volume283
Issue number3
DOIs
Publication statusPublished - Feb 1 2016

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Keywords

  • Papillon-Lefèvre syndrome
  • cathepsin C
  • diagnostic method
  • protease
  • urine analysis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Hamon, Y., Legowska, M., Fergelot, P., Dallet-Choisy, S., Newell, L., Vanderlynden, L., Kord Valeshabad, A., Acrich, K., Kord, H., Charalampos, T., Morice-Picard, F., Surplice, I., Zoidakis, J., David, K., Vlahou, A., Ragunatha, S., Nagy, N., Farkas, K., Széll, M., ... Korkmaz, B. (2016). Analysis of urinary cathepsin C for diagnosing Papillon-Lefèvre syndrome. FEBS Journal, 283(3), 498-509. https://doi.org/10.1111/febs.13605