A novel 18-bp in-frame deletion mutation in RUNX2 causes cleidocranial dysplasia
A novel 18-bp in-frame deletion mutation in RUNX2 causes cleidocranial dysplasia
复制标题
RUNX2 中一种新的 18 bp 框内缺失突变会导致锁骨颅骨发育不良。
DOI：
10.1016/j.archoralbio.2017.10.020
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发表时间：
2018-12-01
影响因子：
3
通讯作者：
Feng, Hailan
中科院分区：
文献类型：
--
作者：
Zeng, Li;Wei, Jiahui;Feng, Hailan
目的：已知 Runt 相关转录因子 2 (RUNX2) 基因会导致罕见的常染色体显性骨骼疾病锁骨颅骨发育不良 (CCD)。在这里，我们探索了中国 CCD 患者 RUNX2 基因中的一个新的大缺失以及与该突变相关的功能。 设计：从外周血中提取基因组 DNA 并进行 DNA 测序。采用Sanger测序对RUNX2基因进行突变分析。通过进行保守性分析、二级结构分析、亚细胞定位研究和报告基因测定来研究与 RUNX2 突变相关的功能。结果：我们鉴定了一种新的大缺失突变，涉及 RUNX2 基因外显子 2 中的 c.243-260delGGCGGCTGCGGCGGCGGC 突变。保守性和二级结构分析表明，新突变位于QA结构域并改变了RUNX2的结构。亚细胞定位分析表明，新突变体与野生型RUNX2表现出相同的细胞内定位，并且都仅定位于细胞核。而报告基因检测表明，新的突变体严重损害了RUNX2基因的反式激活活性。结论：我们的研究结果表明，新的c.243-260delGGCGGCTGCGGCGGCGGC突变导致了CCD。这些结果扩展了 CCD 患者中 RUNX2 突变的范围，并表明了新突变在 CCD 中的功能作用。
Objectives: Runt-related transcription factor 2 (RUNX2) gene is known to cause rare autosomal dominant skeletal disorder Cleidocranial dysplasia (CCD). Here, we explored a novel, large deletion in RUNX2 gene in a Chinese patient with CCD and the function associated with the mutation.Design: Genomic DNA was extracted from the peripheral blood and subjected to do DNA sequencing. Sanger sequencing was used to do mutational analysis of the RUNX2 gene. Function associated with RUNX2 mutation was investigated by performing conservation analysis, secondary structure analysis, subcellular localization study and reporter assay.Results: We identified a novel, large deletion mutation involving a c.243-260delGGCGGCTGCGGCGGCGGC mutation in exon 2 of the RUNX2 gene. Conservation and secondary structure analysis revealed that the novel mutation located in QA domain and converted the structure of RUNX2. Subcellular localization analysis revealed that the novel mutant showed the same intracellular localization with the wild type of RUNX2, and both of them localized exclusively in the nucleus. While reporter assay indicated the novel mutant severely impaired the transactivation activities of RUNX2 gene.Conclusions: Our findings demonstrated that the novel c.243-260delGGCGGCTGCGGCGGCGGC mutation resulted in CCD. These results extend the spectrum of RUNX2 mutations in CCD patients and suggest a functional role of the novel mutation in CCD.