{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:57:51Z","timestamp":1760057871602,"version":"build-2065373602"},"reference-count":72,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Technology Innovation Action Star Project of Shanghai, China","award":["22YF1443000","81641014","20JC1418800"],"award-info":[{"award-number":["22YF1443000","81641014","20JC1418800"]}]},{"name":"National Natural Science Foundation of China","award":["22YF1443000","81641014","20JC1418800"],"award-info":[{"award-number":["22YF1443000","81641014","20JC1418800"]}]},{"name":"Basic Research Project of Shanghai, China","award":["22YF1443000","81641014","20JC1418800"],"award-info":[{"award-number":["22YF1443000","81641014","20JC1418800"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Congenital bicuspid aortic valve (BAV) signifies the most frequent category of congenital cardiovascular anomaly globally, occurring in approximately 0.5\u20132% 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. Methods: 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. Results: 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&gt;G (p.Ile219Arg) variation of TBX20 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 ANP and the binding ability to the ANP promoter and impaired the intranuclear distribution of TBX20. Conclusions: This investigation maps a new genetic locus (chromosome 7p14) linked to BAV and uncovers TBX20 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.<\/jats:p>","DOI":"10.3390\/diagnostics15050600","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T09:04:49Z","timestamp":1740992689000},"page":"600","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chromosomal Location and Identification of TBX20 as a New Gene Responsible for Familial Bicuspid Aortic Valve"],"prefix":"10.3390","volume":"15","author":[{"given":"Yan-Jie","family":"Li","sequence":"first","affiliation":[{"name":"Department of Cardiology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Fifth People\u2019s Hospital, Fudan University, Shanghai 200240, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Zhe","family":"Bian","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Fifth People\u2019s Hospital, Fudan University, Shanghai 200240, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xing-Yuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen-Xi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Fifth People\u2019s Hospital, Fudan University, Shanghai 200240, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Arrhythmias, Ministry of Education of China, School of Medicine, Tongji University, Shanghai 200092, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xing-Biao","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying-Jia","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Fifth People\u2019s Hospital, Fudan University, Shanghai 200240, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0291-8395","authenticated-orcid":false,"given":"Yi-Qing","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Fifth People\u2019s Hospital, Fudan University, Shanghai 200240, China"},{"name":"Cardiovascular Research Laboratory, Shanghai Fifth People\u2019s Hospital, Fudan University, Shanghai 200240, China"},{"name":"Central Laboratory, Shanghai Fifth People\u2019s Hospital, Fudan University, Shanghai 200240, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ri-Tai","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1038\/s41467-023-37110-x","article-title":"Variations in the poly-histidine repeat motif of HOXA1 contribute to bicuspid aortic valve in mouse and zebrafish","volume":"14","author":"Odelin","year":"2023","journal-title":"Nat. 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