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J Hum Genet. 2019 Jul;64(7):689-694. doi: 10.1038/s10038-019-0615-3. Epub 2019 May 8.

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

Author information

1
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, Université de Strasbourg, 4 rue Kirschleger, 67085, Strasbourg, France.
2
Département d'Odontologie Pédiatrique, UFR Odontologie, Université de Nantes, Nantes, France.
3
Unité d'Investigation Clinique Odontologie (UIC), CSERD Nantes, CHU de Nantes, France.
4
INSERM, UMR 1246, MethodS in Patients-centered outcomes and HEalth ResEarch, Nantes, France.
5
European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridge, CD10 1SD, UK.
6
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
7
Service de Génétique Médicale, Hôpital Hôtel-Dieu, CHU de Nantes, Nantes, France.
8
Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.
9
Pôle de Médecine et Chirurgie Bucco-Dentaires, Centre de Référence des Manifestations Odontologiques des Maladies Rares, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
10
Institut de Génétique et de Biologie Moléculaire and Cellulaire, CNRS UMR7104, INSERM U964, Centre Européen de Recherche en Biologie et en Médecine, Université de Strasbourg, Illkirch, France.
11
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, Université de Strasbourg, 4 rue Kirschleger, 67085, Strasbourg, France. siamak@unistra.fr.
12
Service d'Immunologie Biologique, Plateau Technique de Biologie, Pôle de Biologie, Nouvel Hôpital Civil, 1 place de l'Hôpital, 67091, Strasbourg, France. siamak@unistra.fr.
13
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, Université de Strasbourg, 4 rue Kirschleger, 67085, Strasbourg, France. carapito@unistra.fr.
14
Service d'Immunologie Biologique, Plateau Technique de Biologie, Pôle de Biologie, Nouvel Hôpital Civil, 1 place de l'Hôpital, 67091, Strasbourg, France. carapito@unistra.fr.

Abstract

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.

PMID:
31068678
DOI:
10.1038/s10038-019-0615-3
[Indexed for MEDLINE]

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