title: Dental and extra-oral clinical features in 41 patients with WNT10A gene mutations: A multicentric genotype-phenotype study.
abstract: WNT10A gene encodes a canonical wingless pathway signaling molecule involved in cell fate specification as well as morphogenetic patterning of the developing ectoderm, nervous system, skeleton, and tooth. In patients, WNT10A mutations are responsible for ectodermal-derived pathologies including isolated hypo-oligodontia, tricho-odonto-onycho-dermal dysplasia and Schöpf-Schulz-Passarge syndrome (SSPS). Here we describe the dental, ectodermal, and extra-ectodermal phenotypic features of a cohort of 41 patients from 32 unrelated families. Correlations with WNT10A molecular status (heterozygous carrier, compound heterozygous, homozygous) and patient's phenotypes were performed. Mild to severe oligodontia was observed in all patients bearing biallelic WNT10A mutations. However, patients with compound heterozygous mutations presented no significant difference in phenotypes compared with homozygous individuals. Anomalies in tooth morphology were frequently observed with heterozygous patients displaying hypodontia. No signs of SSPS, especially eyelids cysts, were detected in our cohort. Interestingly, extra-ectodermal signs consisted of skeletal, neurological and vascular anomalies, the latter suggesting a wider phenotypic spectrum associated with WNT10A mutations. Indeed, the Wnt pathway plays a crucial role in skeletal development, lipid metabolism, and neurogenesis, potentially explaining patient's clinical manifestations.
authors.affiliation: ADES UMR 7268, Hôpital Timone, Service Odontologie, Aix Marseille University, APHM, Marseille, France.
authors.forename: C
authors.initials: C
authors.lastname: Tardieu
authors.affiliation: Pôle de Médecine et Chirurgie Bucco-Dentaires, Centre de Référence des Manifestations Odontologiques des Maladies Rares, O Rares, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.|Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.
authors.forename: S
authors.initials: S
authors.lastname: Jung
authors.affiliation: CNRS UMR7104, INSERM U964, Institut de Génétique et de Biologie Moléculaire and Cellulaire, Centre Européen de Recherche en Biologie et en Médecine, Université de Strasbourg, Illkirch, France.
authors.forename: K
authors.initials: K
authors.lastname: Niederreither
authors.affiliation: Medical Genetics Laboratory, INSERM U1112, Translational Medicine federation (FMTS), Alsace Medical Genetics Institute, Strasbourg, France.
authors.forename: M
authors.initials: M
authors.lastname: Prasad
authors.affiliation: Reference Center for Genodermatosis, Necker Hospital, AP-HP, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Hadj-Rabia
authors.affiliation: INSERM GMGF, UMR-S910, Aix-Marseille University, Marseille, France.|Department of Medical Genetics, Reference Center for Developmental Anomalies, APHM, Hôpital Timone, Marseille, France.
authors.forename: N
authors.initials: N
authors.lastname: Philip
authors.affiliation: Department of Medical Genetics, Reference Center for Developmental Anomalies, APHM, Hôpital Timone, Marseille, France.
authors.forename: A
authors.initials: A
authors.lastname: Mallet
authors.affiliation: Department of Medical Genetics, Reference Center for Developmental Anomalies, APHM, Hôpital Timone, Marseille, France.
authors.forename: E
authors.initials: E
authors.lastname: Consolino
authors.affiliation: Department of Pediatric Dentistry, Libanese University, Beyrouth, Lebanon.
authors.forename: E
authors.initials: E
authors.lastname: Sfeir
authors.affiliation: Department of Pediatric Dentistry, Libanese University, Beyrouth, Lebanon.
authors.forename: B
authors.initials: B
authors.lastname: Noueiri
authors.affiliation: Department of Medical Genetics, University Hospital, Toulouse, France.
authors.forename: N
authors.initials: N
authors.lastname: Chassaing
authors.affiliation: Medical Genetics Laboratory, INSERM U1112, Translational Medicine federation (FMTS), Alsace Medical Genetics Institute, Strasbourg, France.
authors.forename: H
authors.initials: H
authors.lastname: Dollfus
authors.affiliation: Pôle de Médecine et Chirurgie Bucco-Dentaires, Centre de Référence des Manifestations Odontologiques des Maladies Rares, O Rares, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.|Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.|INSERM Unit UMR 1109, Osteoarticular and Dental Regenerative Nanomedicine, Strasbourg, France.
authors.forename: M C
authors.initials: MC
authors.lastname: Manière
authors.affiliation: Pôle de Médecine et Chirurgie Bucco-Dentaires, Centre de Référence des Manifestations Odontologiques des Maladies Rares, O Rares, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.|Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.|CNRS UMR7104, INSERM U964, Institut de Génétique et de Biologie Moléculaire and Cellulaire, Centre Européen de Recherche en Biologie et en Médecine, Université de Strasbourg, Illkirch, France.
authors.forename: A
authors.initials: A
authors.lastname: Bloch-Zupan
authors.affiliation: Pôle de Médecine et Chirurgie Bucco-Dentaires, Centre de Référence des Manifestations Odontologiques des Maladies Rares, O Rares, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.|Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.|CNRS UMR7104, INSERM U964, Institut de Génétique et de Biologie Moléculaire and Cellulaire, Centre Européen de Recherche en Biologie et en Médecine, Université de Strasbourg, Illkirch, France.|INSERM Unit UMR 1109, Osteoarticular and Dental Regenerative Nanomedicine, Strasbourg, France.
authors.forename: F
authors.identifier: http://orcid.org/0000-0002-8078-2406
authors.initials: F
authors.lastname: Clauss
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D015331:Cohort Studies; D054893:Cone-Beam Computed Tomography; D004475:Ectoderm / Q000473:pathology; D056726:Genetic Association Studies; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008334:Mandible / Q000473:pathology; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D014070:Tooth / Q000000981:diagnostic imaging / Q000473:pathology*; D051153:Wnt Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C484142:WNT10A protein, human; D051153:Wnt Proteins
keywords: WNT10A mutation; bone; dental phenotype; extra-ectodermal signs; oligodontia