title: Role of the RUNX2 p.R225Q mutation in cleidocranial dysplasia: a rare presentation and an analysis of the RUNX2 protein structure.
abstract: Cleidocranial dysplasia (CCD; MIM 119600) is an autosomal dominant hereditary disorder of skeletal features whose characteristic clinical symptoms are caused by mutations in the RUNX2 gene. Varying degrees of clavicular hypoplasia and dental abnormalities are the most prominent features of this disorder. In this study, we presented a Chinese family that included 4 individuals with a p.R225Q mutation in the RUNX2 gene and characteristic CCD phenotypes. Through structural analysis of the p.R225Q mutation in the RUNX2 protein, we determined that the location of this mutation has the potential to affect DNA binding by RUNX2. The proband in this CCD-affected family showed a specific clinical phenotype of CCD that included a median pseudo-cleft palate, which is a presentation of this mutation that has not been reported previously. On the basis of the structural analysis, this study further demonstrated that the p.R225Q mutation abolished DNA binding by RUNX2 and its results also suggested that other genetic and/or environmental factors could affect the CCD phenotypes.
authors.affiliation: Department of Pediatric Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, China.
authors.forename: L Z
authors.initials: LZ
authors.lastname: Wu
authors.affiliation: Third Military Medical University, Chongqing, China.
authors.forename: W Q
authors.initials: WQ
authors.lastname: Su
authors.affiliation: Department of Pediatric Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, China.
authors.forename: Y F
authors.initials: YF
authors.lastname: Liu
authors.affiliation: Department of Pediatric Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, China.
authors.forename: X
authors.initials: X
authors.lastname: Ge
authors.affiliation: Department of Pediatric Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pediatric Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, China wxjingpd@hotmail.com.
authors.forename: X J
authors.initials: XJ
authors.lastname: Wang
mesh_terms: D000328:Adult; D001120:Arginine / Q000378:metabolism*; D044466:Asian People / Q000235:genetics; D001665:Binding Sites; D002648:Child; D002973:Cleidocranial Dysplasia / Q000235:genetics / Q000473:pathology*; D050659:Core Binding Factor Alpha 1 Subunit / Q000737:chemistry* / Q000235:genetics*; D005260:Female; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D020125:Mutation, Missense; D010375:Pedigree
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human; D005973:Glutamine; D001120:Arginine