Wu L Z, Su W Q, Liu Y F, Ge X, Zhang Y, Wang X J
Department of Pediatric Dentistry, School of Stomatology, The Fourth Military Medical University, Xi'an, China.
Third Military Medical University, Chongqing, China.
Genet Mol Res. 2014 Feb 27;13(1):1187-94. doi: 10.4238/2014.February.27.3.
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.
锁骨颅骨发育不全症（CCD；MIM 119600）是一种常染色体显性遗传性骨骼疾病，其特征性临床症状由RUNX2基因突变引起。不同程度的锁骨发育不全和牙齿异常是该疾病最突出的特征。在本研究中，我们展示了一个中国家庭，其中4名个体存在RUNX2基因的p.R225Q突变以及典型的CCD表型。通过对RUNX2蛋白中p.R225Q突变的结构分析，我们确定该突变的位置有可能影响RUNX2与DNA的结合。这个受CCD影响家庭中的先证者表现出特定的CCD临床表型，包括正中假性腭裂，这是该突变的一种此前未被报道的表现形式。基于结构分析，本研究进一步证明p.R225Q突变消除了RUNX2与DNA的结合，其结果还表明其他遗传和/或环境因素可能影响CCD表型。
