Homozygosity mapping and candidate prioritization identify mutations, missed by whole-exome sequencing, in SMOC2, causing major dental developmental defects |
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| Authors: | Bloch-Zupan Agnès Jamet Xavier Etard Christelle Laugel Virginie Muller Jean Geoffroy Véronique Strauss Jean-Pierre Pelletier Valérie Marion Vincent Poch Olivier Strahle Uwe Stoetzel Corinne Dollfus Hélène |
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| Affiliation: | 1Faculty of Dentistry, University of Strasbourg, 1 place de l'Hôpital, Strasbourg 67000, France;2Reference Centre for Orodental Manifestations of Rare Diseases, Service de Médecine et Chirurgie Buccale, Hôpitaux Universitaires de Strasbourg, Strasbourg 67000, France;3Development and Stem Cells Program, collaboration among Institute of Genetics and Molecular and Cellular Biology (IGBMC), Institut National de la Santé et de la Recherche Médicale (Inserm; U964) and Centre National de la Recherche Scientifique (CNRS; UMR #7104), Illkirch 67400, France;4Institut für Toxikologie und Genetik Campus Nord, Karlsruher Institut für Technologie, Hermann-von-Helmholtz-Platz 1, Eggenstein-Leopoldshafen 76344, Germany;5Integrative Genomics and Bioinformatics Laboratory, collaboration among Inserm (U964), CNRS (UMR #7104), and Université de Strasbourg, Illkirch 67400, France;6Cabinet Dentaire, 34 rue Paul Cézanne, Mulhouse 68100, France;7Service de Génétique Médicale, Hôpitaux Universitaires de Strasbourg, Strasbourg 67000, France;8Equipe d'Accueil 3949, Inserm-Avenir, Laboratoire Physiopathologie des Syndromes Rares Héréditaires, Faculté de Médecine, Université de Strasbourg, 11 rue Humann, Strasbourg 67000, France |
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| Abstract: | Inherited dental malformations constitute a clinically and genetically heterogeneous group of disorders. Here, we report on a severe developmental dental defect that results in a dentin dysplasia phenotype with major microdontia, oligodontia, and shape abnormalities in a highly consanguineous family. Homozygosity mapping revealed a unique zone on 6q27-ter. The two affected children were found to carry a homozygous mutation in SMOC2. Knockdown of smoc2 in zebrafish showed pharyngeal teeth that had abnormalities reminiscent of the human phenotype. Moreover, smoc2 depletion in zebrafish affected the expression of three major odontogenesis genes: dlx2, bmp2, and pitx2. |
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