Wei Wei , Bojian Li , Fen Li , Kun Sun , Xuechao Jiang , Rang Xu
{"title":"在先天性心脏病患者中发现的 FOXC1 和 FOXC2 变异","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><p>Conotruncal heart defects (CTD), subtypes of congenital heart disease, result from abnormal cardiac outflow tract development (OFT). <em>FOXC1</em> and <em>FOXC2</em> 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 <em>FOXC1</em> and three in <em>FOXC2</em> 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 <em>TBX1</em> enhancer in two <em>FOXC1</em> variants and three <em>FOXC2</em> variants. This might result from the altered DNA-binding abilities of mutant proteins. These results indicate that functionally impaired <em>FOXC1</em> and <em>FOXC2</em> variants may contribute to the occurrence of CTD.</p></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":"{\"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><p>Conotruncal heart defects (CTD), subtypes of congenital heart disease, result from abnormal cardiac outflow tract development (OFT). <em>FOXC1</em> and <em>FOXC2</em> 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 <em>FOXC1</em> and three in <em>FOXC2</em> 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 <em>TBX1</em> enhancer in two <em>FOXC1</em> variants and three <em>FOXC2</em> variants. This might result from the altered DNA-binding abilities of mutant proteins. These results indicate that functionally impaired <em>FOXC1</em> and <em>FOXC2</em> variants may contribute to the occurrence of CTD.</p></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}","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}
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.
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.