title: Patients with isolated oligo/hypodontia caused by RUNX2 duplication.
abstract: Loss-of-function mutations of RUNX2 are responsible for cleidocranial dysplasia, an autosomal dominant disorder characterized by delayed closure of cranial sutures, aplastic or hypoplastic clavicles, moderate short stature and supernumerary teeth. By contrast, an increased gene dosage is expected for duplication of the entire RUNX2 sequence and thus, a phenotype different from cleidocranial dysplasia. To date, two cousins with a duplication including the entire RUNX2 sequence in addition to MIR586, CLIC5 and the 5' half of SUPT3H have been reported. These patients presented with metopic synostosis and hypodontia. Here, we report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. Interestingly, the mother and one child had isolated hypodontia without craniosynostosis, broadening the phenotype observed in patients with such duplications.
authors.affiliation: Service de Génétique, Laboratoire de cytogénétique, CHU de Caen, Caen, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Molin
authors.affiliation: Departement d'odontologie pédiatrique, faculté de chirurgie dentaire, Nantes, France.|Service d'odontologie conservatrice et pédiatrique, CHU de Nantes, Nantes, France.
authors.forename: Serena
authors.initials: S
authors.lastname: Lopez-Cazaux
authors.affiliation: CHU Nantes, Service de Génétique Médicale, Nantes, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Pichon
authors.affiliation: CHU Nantes, Service de Génétique Médicale, Nantes, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Vincent
authors.affiliation: CHU Nantes, Service de Génétique Médicale, Nantes, France.|INSERM, UMR-957, Laboratoire de physiopathologie de la résorption osseuse et thérapie des tumeurs osseuses primitives, Nantes, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Isidor
authors.affiliation: CHU Nantes, Service de Génétique Médicale, Nantes, France.|INSERM, UMR-957, Laboratoire de physiopathologie de la résorption osseuse et thérapie des tumeurs osseuses primitives, Nantes, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Le Caignec
mesh_terms: D000293:Adolescent; D000328:Adult; D000848:Anodontia / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002648:Child; D055028:Comparative Genomic Hybridization; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D003398:Craniosynostoses / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D005260:Female; D018628:Gene Dosage; D020440:Gene Duplication; D015870:Gene Expression; D006801:Humans; D008297:Male; D010375:Pedigree; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human; C115819:SUPT3H protein, human; D014157:Transcription Factors
keywords: CGH; RUNX2; craniosynostosis; duplication; oligodontia