Analysis of urinary cathepsin C for diagnosing Papillon-Lefèvre syndrome.
FEBS J. 2016-01-04; 283(3): 498-509
DOI: 10.1111/febs.13605
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1. FEBS J. 2016 Feb;283(3):498-509. doi: 10.1111/febs.13605. Epub 2016 Jan 4.
Analysis of urinary cathepsin C for diagnosing Papillon-Lefèvre syndrome.
Hamon Y(1)(2)(3)(4), Legowska M(5), Fergelot P(6)(7)(8), Dallet-Choisy S(1)(2),
Newell L(9), Vanderlynden L(1)(2), Kord Valeshabad A(10), Acrich K(11), Kord
H(12), Charalampos T(9), Morice-Picard F(13), Surplice I(9), Zoidakis J(14),
David K(11), Vlahou A(14), Ragunatha S(15), Nagy N(16)(17)(18), Farkas
K(16)(17)(18), Széll M(16)(17)(18), Goizet C(6)(8), Schacher B(19), Battino
M(20)(21), Al Farraj Aldosari A(22), Wang X(23), Liu Y(24), Marchand-Adam
S(1)(2), Lesner A(5), Kara E(25), Korkmaz-Icöz S(26), Moss C(9)(27), Eickholz
P(19), Taieb A(13), Kavukcu S(28), Jenne DE(3)(4), Gauthier F(1)(2), Korkmaz
B(1)(2).
Author information:
(1)INSERM U-1100 « Centre d’Etude des Pathologies Respiratoires », Tours, France.
(2)Université François Rabelais, Tours, France.
(3)Comprehensive Pneumology Center, Institute of Lung Biology and Disease (iLBD),
German Center for Lung Research (DZL), Munich, Germany.
(4)Max Planck Institute of Neurobiology, Planegg-Martinsried, Germany.
(5)Faculty of Chemistry, University of Gdansk, Gdansk, Poland.
(6)Service de Génétique Médicale, Hôpital Pellegrin, CHU Bordeaux, France.
(7)Centre de Référence des Anomalies du Développement Embryonnaire, Bordeaux,
France.
(8)INSERM U-1211, Laboratoire Maladies Rares: Génétique et Métabolisme,
Université de Bordeaux, France.
(9)Birmingham Children’s Hospital, UK.
(10)University of Colorado Denver, Aurora, CO, USA.
(11)Metropolitan Hospital Center, Medical Genetics Clinic, New York, NY, USA.
(12)Bone Joint and Connective Tissue Disease Research Center (BJCRC), Department
of Rheumatology, Faculty of Medicine, Golestan University of Medical Sciences,
Gorgan, Iran.
(13)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.
(14)Biotechnology Division, Biomedical Research Foundation, Academy of Athens,
Greece.
(15)Department of Dermatology, Venereology, and Leprosy, Sri Siddhartha Medical
College, Tumkur, India.
(16)Department of Medical Genetics, University of Szeged, Hungary.
(17)MTA SZTE Dermatological Research Group, University of Szeged, Hungary.
(18)Department of Dermatology and Allergology, University of Szeged, Hungary.
(19)Department of Periodontology, Johann Wolfgang Goethe-University Frankfurt,
Germany.
(20)Department of Clinical Sciences, Università Politecnica delle Marche, Ancona,
Italy.
(21)Centre for Nutrition & Health, Universidad Europea del Atlantico, Santander,
Spain.
(22)Department of Prosthetic, College of Dentistry, King Saud University, Riyadh,
Kingdom of Saudi Arabia.
(23)Department of Oral Medicine and Periodontology, School of Stomatology, The
Fourth Military Medical University, Xi’an, Shaanxi, China.
(24)Department of Periodontology, PLA 309 Hospital, Beijing, China.
(25)ReproPharm, Centre INRA-Val de Loire, Domaine de l’Orfrasière, Nouzilly,
France.
(26)Department of Cardiac Surgery, Heidelberg University Hospital, Germany.
(27)University of Birmingham, Edgbaston, UK.
(28)Division of Pediatric Nephrology, Department of Pediatrics, School of
Medicine, Dokuz Eylül University, İzmir, Turkey.
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.
© 2015 FEBS.
DOI: 10.1111/febs.13605
PMID: 26607765 [Indexed for MEDLINE]