title: Homozygosity mapping and candidate prioritization identify mutations, missed by whole-exome sequencing, in SMOC2, causing major dental developmental defects.
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.
authors.affiliation: Faculty of Dentistry, University of Strasbourg, 1 place de l'Hôpital, Strasbourg, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Bloch-Zupan
authors.forename: Xavier
authors.initials: X
authors.lastname: Jamet
authors.forename: Christelle
authors.initials: C
authors.lastname: Etard
authors.forename: Virginie
authors.initials: V
authors.lastname: Laugel
authors.forename: Jean
authors.initials: J
authors.lastname: Muller
authors.forename: Véronique
authors.initials: V
authors.lastname: Geoffroy
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Strauss
authors.forename: Valérie
authors.initials: V
authors.lastname: Pelletier
authors.forename: Vincent
authors.initials: V
authors.lastname: Marion
authors.forename: Olivier
authors.initials: O
authors.lastname: Poch
authors.forename: Uwe
authors.initials: U
authors.lastname: Strahle
authors.forename: Corinne
authors.initials: C
authors.lastname: Stoetzel
authors.forename: Hélène
authors.initials: H
authors.lastname: Dollfus
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D003241:Consanguinity; D003805:Dentin Dysplasia / Q000175:diagnosis / Q000235:genetics*; D059472:Exome; D005260:Female; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D056726:Genetic Association Studies; D006720:Homozygote; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics; D010375:Pedigree; D017422:Sequence Analysis, DNA; D014070:Tooth / Q000254:growth & development*; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; C478653:DACT2 protein, human; D009363:Neoplasm Proteins; C476827:SMOC2 protein, human