title: Analysis of urinary cathepsin C for diagnosing Papillon-Lefèvre syndrome.
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.
authors.affiliation: INSERM U-1100 "Centre d'Etude des Pathologies Respiratoires", Tours, France.|Université François Rabelais, Tours, France.|Comprehensive Pneumology Center, Institute of Lung Biology and Disease (iLBD), German Center for Lung Research (DZL), Munich, Germany.|Max Planck Institute of Neurobiology, Planegg-Martinsried, Germany.
authors.forename: Yveline
authors.initials: Y
authors.lastname: Hamon
authors.affiliation: Faculty of Chemistry, University of Gdansk, Gdansk, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Legowska
authors.affiliation: Service de Génétique Médicale, Hôpital Pellegrin, CHU Bordeaux, France.|Centre de Référence des Anomalies du Développement Embryonnaire, Bordeaux, France.|INSERM U-1211, Laboratoire Maladies Rares: Génétique et Métabolisme, Université de Bordeaux, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Fergelot
authors.affiliation: INSERM U-1100 "Centre d'Etude des Pathologies Respiratoires", Tours, France.|Université François Rabelais, Tours, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Dallet-Choisy
authors.affiliation: Birmingham Children's Hospital, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Newell
authors.affiliation: INSERM U-1100 "Centre d'Etude des Pathologies Respiratoires", Tours, France.|Université François Rabelais, Tours, France.
authors.forename: Lise
authors.initials: L
authors.lastname: Vanderlynden
authors.affiliation: University of Colorado Denver, Aurora, CO, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Kord Valeshabad
authors.affiliation: Metropolitan Hospital Center, Medical Genetics Clinic, New York, NY, USA.
authors.forename: Karina
authors.initials: K
authors.lastname: Acrich
authors.affiliation: Bone Joint and Connective Tissue Disease Research Center (BJCRC), Department of Rheumatology, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
authors.forename: Hadi
authors.initials: H
authors.lastname: Kord
authors.affiliation: Birmingham Children's Hospital, UK.
authors.forename: Tsamakis
authors.initials: T
authors.lastname: Charalampos
authors.affiliation: Centre de Référence pour les Maladies Rares de la Peau, Service de Dermatologie Adulte et Pédiatrique, CHU de Bordeaux and INSERM U-1035, University of Bordeaux, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Morice-Picard
authors.affiliation: Birmingham Children's Hospital, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Surplice
authors.affiliation: Biotechnology Division, Biomedical Research Foundation, Academy of Athens, Greece.
authors.forename: Jerome
authors.initials: J
authors.lastname: Zoidakis
authors.affiliation: Metropolitan Hospital Center, Medical Genetics Clinic, New York, NY, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: David
authors.affiliation: Biotechnology Division, Biomedical Research Foundation, Academy of Athens, Greece.
authors.forename: Antonia
authors.initials: A
authors.lastname: Vlahou
authors.affiliation: Department of Dermatology, Venereology, and Leprosy, Sri Siddhartha Medical College, Tumkur, India.
authors.forename: Shivanna
authors.initials: S
authors.lastname: Ragunatha
authors.affiliation: Department of Medical Genetics, University of Szeged, Hungary.|MTA SZTE Dermatological Research Group, University of Szeged, Hungary.|Department of Dermatology and Allergology, University of Szeged, Hungary.
authors.forename: Nikoletta
authors.initials: N
authors.lastname: Nagy
authors.affiliation: Department of Medical Genetics, University of Szeged, Hungary.|MTA SZTE Dermatological Research Group, University of Szeged, Hungary.|Department of Dermatology and Allergology, University of Szeged, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Farkas
authors.affiliation: Department of Medical Genetics, University of Szeged, Hungary.|MTA SZTE Dermatological Research Group, University of Szeged, Hungary.|Department of Dermatology and Allergology, University of Szeged, Hungary.
authors.forename: Márta
authors.initials: M
authors.lastname: Széll
authors.affiliation: Service de Génétique Médicale, Hôpital Pellegrin, CHU Bordeaux, France.|INSERM U-1211, Laboratoire Maladies Rares: Génétique et Métabolisme, Université de Bordeaux, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Goizet
authors.affiliation: Department of Periodontology, Johann Wolfgang Goethe-University Frankfurt, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Schacher
authors.affiliation: Department of Clinical Sciences, Università Politecnica delle Marche, Ancona, Italy.|Centre for Nutrition & Health, Universidad Europea del Atlantico, Santander, Spain.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Battino
authors.affiliation: Department of Prosthetic, College of Dentistry, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Al Farraj Aldosari
authors.affiliation: Department of Oral Medicine and Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Xinwen
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Periodontology, PLA 309 Hospital, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: INSERM U-1100 "Centre d'Etude des Pathologies Respiratoires", Tours, France.|Université François Rabelais, Tours, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Marchand-Adam
authors.affiliation: Faculty of Chemistry, University of Gdansk, Gdansk, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Lesner
authors.affiliation: ReproPharm, Centre INRA-Val de Loire, Domaine de l'Orfrasière, Nouzilly, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Kara
authors.affiliation: Department of Cardiac Surgery, Heidelberg University Hospital, Germany.
authors.forename: Sevil
authors.initials: S
authors.lastname: Korkmaz-Icöz
authors.affiliation: Birmingham Children's Hospital, UK.|University of Birmingham, Edgbaston, UK.
authors.forename: Celia
authors.initials: C
authors.lastname: Moss
authors.affiliation: Department of Periodontology, Johann Wolfgang Goethe-University Frankfurt, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Eickholz
authors.affiliation: Centre de Référence pour les Maladies Rares de la Peau, Service de Dermatologie Adulte et Pédiatrique, CHU de Bordeaux and INSERM U-1035, University of Bordeaux, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Taieb
authors.affiliation: Division of Pediatric Nephrology, Department of Pediatrics, School of Medicine, Dokuz Eylül University, İzmir, Turkey.
authors.forename: Salih
authors.initials: S
authors.lastname: Kavukcu
authors.affiliation: Comprehensive Pneumology Center, Institute of Lung Biology and Disease (iLBD), German Center for Lung Research (DZL), Munich, Germany.|Max Planck Institute of Neurobiology, Planegg-Martinsried, Germany.
authors.forename: Dieter E
authors.initials: DE
authors.lastname: Jenne
authors.affiliation: INSERM U-1100 "Centre d'Etude des Pathologies Respiratoires", Tours, France.|Université François Rabelais, Tours, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Gauthier
authors.affiliation: INSERM U-1100 "Centre d'Etude des Pathologies Respiratoires", Tours, France.|Université François Rabelais, Tours, France.
authors.forename: Brice
authors.initials: B
authors.lastname: Korkmaz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020789:Cathepsin C / Q000235:genetics / Q000378:metabolism / Q000652:urine*; D002648:Child; D002675:Child, Preschool; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D010214:Papillon-Lefevre Disease / Q000175:diagnosis* / Q000652:urine*; D010641:Phenotype; D055815:Young Adult
chemical_list: C533918:CTSC protein, human; D020789:Cathepsin C
keywords: Papillon-Lefèvre syndrome; cathepsin C; diagnostic method; protease; urine analysis