Chromosomal Location and Identification of <i>TBX20</i> as a New Gene Responsible for Familial Bicuspid Aortic Valve
<b>Background/Objectives:</b> Congenital bicuspid aortic valve (BAV) signifies the most frequent category of congenital cardiovascular anomaly globally, occurring in approximately 0.5–2% of the general population worldwide. BAV is a major cause of thoracic aortopathy, encompassing aortic...
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2025-03-01
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| author | Yan-Jie Li Su Zou Yi-Zhe Bian Xing-Yuan Liu Chen-Xi Yang Li Li Xing-Biao Qiu Ying-Jia Xu Yi-Qing Yang Ri-Tai Huang |
| author_facet | Yan-Jie Li Su Zou Yi-Zhe Bian Xing-Yuan Liu Chen-Xi Yang Li Li Xing-Biao Qiu Ying-Jia Xu Yi-Qing Yang Ri-Tai Huang |
| author_sort | Yan-Jie Li |
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| description | <b>Background/Objectives:</b> Congenital bicuspid aortic valve (BAV) signifies the most frequent category of congenital cardiovascular anomaly globally, occurring in approximately 0.5–2% of the general population worldwide. BAV is a major cause of thoracic aortopathy, encompassing aortic stenosis, aortic root dilation with regurgitation, aortic dissection, and aortic aneurysms, consequently leading to substantial late-onset morbidity and mortality. Accumulating evidence convincingly demonstrates the strong genetic basis underpinning BAV, though the inheritable reasons responsible for BAV in most patients remain largely obscure. <b>Methods:</b> A genome-wide genotyping with 400 polymorphic genetic markers followed by linkage analysis, haplotype assay, and sequencing analysis of candidate genes was conducted in a 4-generation BAV kindred of 47 individuals. Biochemical assays were performed to evaluate the functional effect of the identified mutation on TBX20. <b>Results:</b> A novel BAV-causative locus was mapped to chromosome 7p14. A sequencing assay of the genes within the mapped chromosomal region (locus) unveiled that only the c.656T>G (p.Ile219Arg) variation of <i>TBX20</i> was in co-segregation with BAV in the entire pedigree. The missense mutation was not uncovered in 322 healthy persons employed as control individuals. Functional deciphers revealed that the mutation significantly decreased the transcriptional activation of the representative target gene <i>ANP</i> and the binding ability to the <i>ANP</i> promoter and impaired the intranuclear distribution of TBX20. <b>Conclusions:</b> This investigation maps a new genetic locus (chromosome 7p14) linked to BAV and uncovers <i>TBX20</i> as a novel causative gene for familial BAV, adding more insight into the mechanisms underlying BAV and providing a molecular target for the individualized management of BAV. |
| format | Article |
| id | doaj-art-eea532b0a8934d3d9ffebd5ab9808d3c |
| institution | DOAJ |
| issn | 2075-4418 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
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| series | Diagnostics |
| spelling | doaj-art-eea532b0a8934d3d9ffebd5ab9808d3c2025-08-20T02:58:58ZengMDPI AGDiagnostics2075-44182025-03-0115560010.3390/diagnostics15050600Chromosomal Location and Identification of <i>TBX20</i> as a New Gene Responsible for Familial Bicuspid Aortic ValveYan-Jie Li0Su Zou1Yi-Zhe Bian2Xing-Yuan Liu3Chen-Xi Yang4Li Li5Xing-Biao Qiu6Ying-Jia Xu7Yi-Qing Yang8Ri-Tai Huang9Department of Cardiology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaDepartment of Cardiology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai 200240, ChinaDepartment of Cardiology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai 200240, ChinaDepartment of Pediatrics, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, ChinaDepartment of Cardiology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai 200240, ChinaKey Laboratory of Arrhythmias, Ministry of Education of China, School of Medicine, Tongji University, Shanghai 200092, ChinaDepartment of Cardiology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaDepartment of Cardiology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai 200240, ChinaDepartment of Cardiology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai 200240, ChinaDepartment of Cardiovascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China<b>Background/Objectives:</b> Congenital bicuspid aortic valve (BAV) signifies the most frequent category of congenital cardiovascular anomaly globally, occurring in approximately 0.5–2% of the general population worldwide. BAV is a major cause of thoracic aortopathy, encompassing aortic stenosis, aortic root dilation with regurgitation, aortic dissection, and aortic aneurysms, consequently leading to substantial late-onset morbidity and mortality. Accumulating evidence convincingly demonstrates the strong genetic basis underpinning BAV, though the inheritable reasons responsible for BAV in most patients remain largely obscure. <b>Methods:</b> A genome-wide genotyping with 400 polymorphic genetic markers followed by linkage analysis, haplotype assay, and sequencing analysis of candidate genes was conducted in a 4-generation BAV kindred of 47 individuals. Biochemical assays were performed to evaluate the functional effect of the identified mutation on TBX20. <b>Results:</b> A novel BAV-causative locus was mapped to chromosome 7p14. A sequencing assay of the genes within the mapped chromosomal region (locus) unveiled that only the c.656T>G (p.Ile219Arg) variation of <i>TBX20</i> was in co-segregation with BAV in the entire pedigree. The missense mutation was not uncovered in 322 healthy persons employed as control individuals. Functional deciphers revealed that the mutation significantly decreased the transcriptional activation of the representative target gene <i>ANP</i> and the binding ability to the <i>ANP</i> promoter and impaired the intranuclear distribution of TBX20. <b>Conclusions:</b> This investigation maps a new genetic locus (chromosome 7p14) linked to BAV and uncovers <i>TBX20</i> as a novel causative gene for familial BAV, adding more insight into the mechanisms underlying BAV and providing a molecular target for the individualized management of BAV.https://www.mdpi.com/2075-4418/15/5/600congenital heart diseasecongenital bicuspid aortic valvehuman geneticsfunctional genomics<i>TBX20</i>biochemical assay |
| spellingShingle | Yan-Jie Li Su Zou Yi-Zhe Bian Xing-Yuan Liu Chen-Xi Yang Li Li Xing-Biao Qiu Ying-Jia Xu Yi-Qing Yang Ri-Tai Huang Chromosomal Location and Identification of <i>TBX20</i> as a New Gene Responsible for Familial Bicuspid Aortic Valve Diagnostics congenital heart disease congenital bicuspid aortic valve human genetics functional genomics <i>TBX20</i> biochemical assay |
| title | Chromosomal Location and Identification of <i>TBX20</i> as a New Gene Responsible for Familial Bicuspid Aortic Valve |
| title_full | Chromosomal Location and Identification of <i>TBX20</i> as a New Gene Responsible for Familial Bicuspid Aortic Valve |
| title_fullStr | Chromosomal Location and Identification of <i>TBX20</i> as a New Gene Responsible for Familial Bicuspid Aortic Valve |
| title_full_unstemmed | Chromosomal Location and Identification of <i>TBX20</i> as a New Gene Responsible for Familial Bicuspid Aortic Valve |
| title_short | Chromosomal Location and Identification of <i>TBX20</i> as a New Gene Responsible for Familial Bicuspid Aortic Valve |
| title_sort | chromosomal location and identification of i tbx20 i as a new gene responsible for familial bicuspid aortic valve |
| topic | congenital heart disease congenital bicuspid aortic valve human genetics functional genomics <i>TBX20</i> biochemical assay |
| url | https://www.mdpi.com/2075-4418/15/5/600 |
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