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Exome sequencing identifies a novel missense variant in CTSC causing nonsyndromic aggressive periodontitis

  • Molitor, Anne1
  • Prud’homme, Tony2, 3, 4
  • Miao, Zhichao5, 6
  • Conrad, Solène7
  • Bloch-Zupan, Agnès8, 9, 10
  • Pichot, Angélique1
  • Hanauer, Antoine1
  • Isidor, Bertrand7
  • Bahram, Seiamak1, 11
  • Carapito, Raphael1, 11
  • 1 Université de Strasbourg, Laboratoire d’ImmunoRhumatologie Moléculaire, plateforme GENOMAX, INSERM UMR_S 1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), LabEx TRANSPLANTEX, 4 rue Kirschleger, Strasbourg, 67085, France , Strasbourg (France)
  • 2 Université de Nantes, Département d’Odontologie Pédiatrique, UFR Odontologie, Nantes, France , Nantes (France)
  • 3 Unité d’Investigation Clinique Odontologie (UIC), CSERD Nantes, CHU de Nantes, France , CHU de Nantes (France)
  • 4 INSERM, UMR 1246, MethodS in Patients-centered outcomes and HEalth ResEarch, Nantes, France , Nantes (France)
  • 5 Wellcome Genome Campus, European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, Cambridge, CD10 1SD, UK , Hinxton (United Kingdom)
  • 6 Wellcome Genome Campus, Wellcome Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK , Hinxton (United Kingdom)
  • 7 Service de Génétique Médicale, Hôpital Hôtel-Dieu, CHU de Nantes, Nantes, France , Nantes (France)
  • 8 Université de Strasbourg, Faculté de Chirurgie Dentaire, Strasbourg, France , Strasbourg (France)
  • 9 Hôpitaux Universitaires de Strasbourg, Pôle de Médecine et Chirurgie Bucco-Dentaires, Centre de Référence des Manifestations Odontologiques des Maladies Rares, Strasbourg, France , Strasbourg (France)
  • 10 Université de Strasbourg, Institut de Génétique et de Biologie Moléculaire and Cellulaire, CNRS UMR7104, INSERM U964, Centre Européen de Recherche en Biologie et en Médecine, Illkirch, France , Illkirch (France)
  • 11 Service d’Immunologie Biologique, Plateau Technique de Biologie, Pôle de Biologie, Nouvel Hôpital Civil, 1 place de l’Hôpital, Strasbourg, 67091, France , Strasbourg (France)
Published Article
Journal of Human Genetics
Springer Nature
Publication Date
May 08, 2019
DOI: 10.1038/s10038-019-0615-3
Springer Nature


Cathepsin C (CatC) is a cysteine protease involved in a variety of immune and inflammatory pathways such as activation of cytotoxicity of various immune cells. Homozygous or compound heterozygous variants in the CatC coding gene CTSC cause different conditions that have in common severe periodontitis. Periodontitis may occur as part of Papillon–Lefèvre syndrome (PLS; OMIM#245000) or Haim–Munk syndrome (HMS; OMIM#245010), or may present as an isolated finding named aggressive periodontitis (AP1; OMIM#170650). AP1 generally affects young children and results in destruction of the periodontal support of the primary dentition. In the present study we report exome sequencing of a three generation consanguineous Turkish family with a recessive form of early-onset AP1. We identified a novel homozygous missense variant in exon 2 of CTSC (NM_148170, c.G302C, p.Trp101Ser) predicted to disrupt protein structure and to be disease causing. This is the first described CTSC variant specific to the nonsyndromic AP1 form. Given the broad phenotypic spectrum associated with CTSC variants, reporting this novel variant gives new insights on genotype/phenotype correlations and might improve diagnosis of patients with early-onset AP1.

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