在先天性心脏病患者中发现的 FOXC1 和 FOXC2 变异

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC

ACS Applied Electronic Materials Pub Date : 2024-04-03 DOI:10.1016/j.ygeno.2024.110840

Wei Wei , Bojian Li , Fen Li , Kun Sun , Xuechao Jiang , Rang Xu

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引用次数: 0

摘要

先天性心脏病的亚型--圆锥形心脏缺损（CTD）是心脏流出道（OFT）发育异常的结果。FOXC1和FOXC2是叉头转录因子家族中关系密切的成员，在心脏流出道的发育过程中起着至关重要的作用。我们确认了它们在小鼠和人类胚胎中的表达模式，并在 605 名散发性 CTD 患者中筛选出了 FOXC1 的四个变体和 FOXC2 的三个变体。Western 印迹显示了变异基因的表达水平，而双荧光素酶报告分析显示，在两个 FOXC1 变异基因和三个 FOXC2 变异基因中，TBX1 增强子的转录能力受到了影响。这可能是由于突变蛋白的 DNA 结合能力发生了改变。这些结果表明，功能受损的 FOXC1 和 FOXC2 变体可能会导致 CTD 的发生。

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Variants in FOXC1 and FOXC2 identified in patients with conotruncal heart defects

Conotruncal heart defects (CTD), subtypes of congenital heart disease, result from abnormal cardiac outflow tract development (OFT). FOXC1 and FOXC2 are closely related members of the forkhead transcription factor family and play essential roles in the development of OFT. We confirmed their expression pattern in mouse and human embryos, identifying four variants in FOXC1 and three in FOXC2 by screening these two genes in 605 patients with sporadic CTD. Western blot demonstrated expression levels, while Dual-luciferase reporter assay revealed affected transcriptional abilities for TBX1 enhancer in two FOXC1 variants and three FOXC2 variants. This might result from the altered DNA-binding abilities of mutant proteins. These results indicate that functionally impaired FOXC1 and FOXC2 variants may contribute to the occurrence of CTD.

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来源期刊

ACS Applied Electronic Materials Multiple-

CiteScore

7.20

自引率

4.30%

发文量

567