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

IF 3.4 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics Pub Date : 2024-04-03 DOI:10.1016/j.ygeno.2024.110840

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

{"title":"Variants in FOXC1 and FOXC2 identified in patients with conotruncal heart defects","authors":"Wei Wei , Bojian Li , Fen Li , Kun Sun , Xuechao Jiang , Rang Xu","doi":"10.1016/j.ygeno.2024.110840","DOIUrl":null,"url":null,"abstract":"<div>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.</div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0888754324000612/pdfft?md5=ac8a1cff7d79eef86060f24a346524d3&pid=1-s2.0-S0888754324000612-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genomics","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0888754324000612","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

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.

查看原文本刊更多论文

在先天性心脏病患者中发现的 FOXC1 和 FOXC2 变异

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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Genomics 生物-生物工程与应用微生物

CiteScore

9.60

自引率

2.30%

发文量

260

审稿时长

60 days

期刊介绍： Genomics is a forum for describing the development of genome-scale technologies and their application to all areas of biological investigation. As a journal that has evolved with the field that carries its name, Genomics focuses on the development and application of cutting-edge methods, addressing fundamental questions with potential interest to a wide audience. Our aim is to publish the highest quality research and to provide authors with rapid, fair and accurate review and publication of manuscripts falling within our scope.