A novel in-frame deletion of the RUNX2 gene causes a classic form of cleidocranial dysplasia
A novel in-frame deletion of the RUNX2 gene causes a classic form of cleidocranial dysplasia
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RUNX2基因的新型框内缺失导致锁骨颅骨发育不良的典型形式
DOI：
10.1007/s00774-013-0456-7
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发表时间：
2013
影响因子：
3.3
通讯作者：
Ishiguro N.
中科院分区：
文献类型：
--
作者：
Mastushita M.;Kitoh H.;Kaneko H.;Mishima K.;Itoh Y.;Tokita Y.;Ishiguro N.
矮小相关转录因子2(RUNX2)是一个生理调节基因，与锁骨颅骨发育不良症的发生发展密切相关。对1例诊断为CCD2的2岁男童的RUNX2基因进行了分子分析，发现RUNX2基因框内9个碱基杂合性缺失(c.593_601delCCTTGACCA，对应于ΔTLT198_200的氨基酸缺失)。ΔTLT198200突变体的转录活性下降的程度与L199F突变体相似，这是以前报道的典型CCDT突变的情况。原子模型分析表明，ΔTLT198200突变取消了RUNX2蛋白与其伴侣亚单位多瘤病毒增强子结合蛋白2β(PEBP2β)的异源二聚化。RUNX2/PEBP2β异二聚化活性的破坏似乎削弱了RUNX2蛋白的功能，从而导致疾病。
The runt-related transcription factor 2 (RUNX2) is a physiological regulatory gene implicated in the development of cleidocranial dysplasia (CCD). Molecular analysis of theRUNX2gene in a 2-year-old boy with a diagnosis of CCD demonstrated a heterozygous in-frame 9-bp deletion (c.593_601delCCTTGACCA, corresponding to the amino-acid deletion p.ΔTLT198_200). Transcription activity of the ΔTLT198_200 mutant decreased in a similar degree to that of the L199F mutant, which was previously reported in the case with classic CCD. Atomic model assessment demonstrated that the ΔTLT198_200 mutation abolished the heterodimerization of the RUNX2 protein with the partner subunit, polyomavirus enhancer-binding protein 2β (PEBP2β). Destruction of RUNX2/PEBP2β heterodimerization activity appears to impair the function of the RUNX2 protein and cause the disease.