分析小说在中国cleidocranial发育不良患者RUNX2突变。
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太阳王刘张X, Y, X, X,郑张C, S
分析小说在中国cleidocranial发育不良患者RUNX2突变。
《公共科学图书馆•综合》。2017年7月24日,12 (7):e0181653。doi: 10.1371 / journal.pone.0181653。eCollection 2017。
- PubMed ID
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28738062 (在PubMed]
- 文摘
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Cleidocranial发育不良(CCD)是一种常染色体显性遗传骨骼疾病特点是脑发育不良,锁骨发育不全和牙科异常。这种疾病主要是由于在RUNX2的杂合突变,一个基因编码一个osteoblast-specific转录因子。在目前的研究中,基因进行突变分析RUNX2四无关的中国患者CCD。四种不同RUNX2突变被发现在这些患者中,包括一个无义突变(c。199 c > T p.Q67X)和三个错义突变(c。338 t > G p。L113R c。557 g > C p。R186T和c。673 c > T p.R225W)。其中,两个突变(c。199 c > T p。Q67X和c。557 g > C p。R186T) were novel and the other two had been reported in previous literatures. Except for Q67X mutation located in the Q/A domain, other three mutations were clustered within the highly conserved Runt domain. Green fluorescent protein (GFP) and RUNX2 fusion protein analyses in vitro showed that nuclear accumulation of RUNX2 protein was disturbed by Q67X mutation, while the other two mutations (c.338T>G p.L113R and c.557G>C p.R186T) had no effects on the subcellular distribution of RUNX2. Luciferase reporter assay demonstrated that all the three novel RUNX2 mutations significantly reduced the transactivation activity of RUNX2 on osteocalcin promoter. Our findings enrich the evidence of molecular genetics that the mutations of RUNX2 gene are responsible for CCD.