title: A novel RUNX2 mutation in cleidocranial dysplasia patients.
abstract: Cleidocranial dysplasia (CCD) is an autosomal-dominant heritable skeletal disease caused by heterozygous mutations in the RUNX2 gene. Here, the RUNX2 gene was analyzed within a CCD family from China, and a novel missense mutation (c. 475G --> C [p.G159R]) was identified. Normal and mutant RUNX2 expression vectors were then constructed and expressed transiently in NIH3T3 cells. Immunofluorescent staining and Western blotting showed that wild-type RUNX2 protein was localized exclusively in the nucleus; however, the mutant protein was found in both the nucleus and the cytoplasm, which demonstrated that transport of the RUNX2 mutant into the nucleus was disturbed by the G159R mutation. Therefore, we suggest that G159 is very important to promote RUNX2 nuclear localization. According to clinical analysis, the patient displays severe dysplasia of bones and relatively low-grade craniofacial abnormality, and we infer that G159 may be vital for normal skeletal development, other than control of tooth number. These findings confirm that mutations in the RUNX2 gene are associated with the pathogenesis of CCD across different ethnic backgrounds.
authors.affiliation: Department of Periodontology, Guangdong Provincial Stomatological Hospital, Southern Medical University, S366 Jiangnan Boulevard, Guangzhou, 510280, PR China.
authors.forename: Dongying
authors.initials: D
authors.lastname: Xuan
authors.forename: Shi
authors.initials: S
authors.lastname: Li
authors.forename: Xiong
authors.initials: X
authors.lastname: Zhang
authors.forename: Lixin
authors.initials: L
authors.lastname: Lin
authors.forename: Chunxian
authors.initials: C
authors.lastname: Wang
authors.forename: Jincai
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001483:Base Sequence; D002681:China; D002973:Cleidocranial Dysplasia / Q000235:genetics* / Q000473:pathology; D050659:Core Binding Factor Alpha 1 Subunit / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005190:Family; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging; D051379:Mice; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D041681:NIH 3T3 Cells; D021381:Protein Transport; D011859:Radiography; D017421:Sequence Analysis
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human