{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTBX5 is a highly conserved T‑box transcription factor that plays a central role in embryonic organogenesis. It is essential for proper cardiac morphogenesis and forelimb identity by regulating key gene‐expression programs. TBX5 contains a well‐defined T‑box DNA–binding domain, distinct nuclear localization signals, and a transactivation domain that together enable it to coordinate transcription and modulate cell cycle and apoptosis. Moreover, TBX5 physically interacts with other cardiac transcription factors—such as GATA4, NKX2‑5, and even factors like HAND2—to drive septation and conduction system development. Structural studies and functional analyses have revealed that mutations disrupting these domains or protein–protein interactions can severely impair TBX5’s function during heart and limb formation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMutations and alterations in TBX5 dosage underlie a spectrum of congenital cardiac defects and conduction abnormalities—including Holt‐Oram syndrome, atrial septal defects, tetralogy of Fallot, and even dilated cardiomyopathy. Both loss‐of‑function and gain‑of‑function mutations have been reported to diminish or abnormally enhance TBX5’s DNA–binding and transcriptional activity, disrupt its cooperative interactions with other cardiac regulators, and lead to defective patterning and arrhythmogenesis. In addition, genomic rearrangements and regulatory mutations (including in TBX5 enhancers) further illustrate its dosage sensitivity. Extensive genetic studies and genome‑wide association analyses have consistently implicated TBX5 variants and copy‐number changes as major risk factors for various forms of congenital heart disease, highlighting its critical role in cardiac development."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "31"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in transcriptional activation, TBX5 is subject to multifaceted regulation. Recent studies have uncovered that TBX5 also participates in pre‑mRNA splicing through its association with splicing factors and interacts with chromatin repressors (such as the NuRD complex) to silence gene programs incompatible with normal cardiac development. In addition, TBX5 expression and activity are modulated by microRNAs—including miR‑10a and miR‑10b—as well as by small molecules (for example, thalidomide, which can disrupt TBX5’s DNA binding and its partnership with HAND2), thereby linking epigenetic control to its dosage‐dependent functions. Furthermore, investigations using human induced pluripotent stem cell–derived cardiomyocytes have delineated complex TBX5‐based gene regulatory networks whose perturbation can ultimately lead to arrhythmias and other cardiac pathologies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "32"}, {"type": "fg_f", "ref": "29"}, {"type": "fg_fs", "start_ref": "34", "end_ref": "39"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ming-Liang He, Ying Chen, Ying Peng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Induction of apoptosis and inhibition of cell growth by developmental regulator hTBX5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0006-291x(02)02142-3"}], "href": "https://doi.org/10.1016/s0006-291x(02"}, {"type": "t", "text": "02142-3) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12237100"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12237100"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Chun Fan, Mugen Liu, Qing Wang "}, {"type": "b", "children": [{"type": "t", "text": "Functional analysis of TBX5 missense mutations associated with Holt-Oram syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M208120200"}], "href": "https://doi.org/10.1074/jbc.M208120200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12499378"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12499378"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Vidu Garg, Irfan S Kathiriya, Robert Barnes, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature01827"}], "href": "https://doi.org/10.1038/nature01827"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12845333"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12845333"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Anita Collavoli, Cathy J Hatcher, Jie He, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TBX5 nuclear localization is mediated by dual cooperative intramolecular signals."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Cell Cardiol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0022-2828(03)00231-1"}], "href": "https://doi.org/10.1016/s0022-2828(03"}, {"type": "t", "text": "00231-1) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14519429"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14519429"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Michael V Zaragoza, Lisa E Lewis, Guifeng Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of the TBX5 transactivating domain and the nuclear localization signal."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2004.01.017"}], "href": "https://doi.org/10.1016/j.gene.2004.01.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15087119"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15087119"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Henner F Farin, Markus Bussen, Martina K Schmidt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptional repression by the T-box proteins Tbx18 and Tbx15 depends on Groucho corepressors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M703724200"}], "href": "https://doi.org/10.1074/jbc.M703724200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17584735"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17584735"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Daniel Levy, Georg B Ehret, Kenneth Rice, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association study of blood pressure and hypertension."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.384"}], "href": "https://doi.org/10.1038/ng.384"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19430479"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19430479"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Jean-François Ouimette, Marisol Lavertu Jolin, Aurore L'honoré, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Divergent transcriptional activities determine limb identity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms1036"}], "href": "https://doi.org/10.1038/ncomms1036"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20975709"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20975709"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Li Wang, Ziqing Liu, Chaoying Yin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Stoichiometry of Gata4, Mef2c, and Tbx5 influences the efficiency and quality of induced cardiac myocyte reprogramming."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCRESAHA.116.305547"}], "href": "https://doi.org/10.1161/CIRCRESAHA.116.305547"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25416133"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25416133"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Deborah A McDermott, Michael C Bressan, Jie He, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TBX5 genetic testing validates strict clinical criteria for Holt-Oram syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pediatr Res (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1203/01.PDR.0000182593.95441.64"}], "href": "https://doi.org/10.1203/01.PDR.0000182593.95441.64"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16183809"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16183809"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Wiktor Borozdin, Ana M Bravo Ferrer Acosta, Michael J Bamshad, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expanding the spectrum of TBX5 mutations in Holt-Oram syndrome: detection of two intragenic deletions by quantitative real time PCR, and report of eight novel point mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.9449"}], "href": "https://doi.org/10.1002/humu.9449"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16917909"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16917909"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Alex V Postma, Judith B A van de Meerakker, Inge B Mathijssen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A gain-of-function TBX5 mutation is associated with atypical Holt-Oram syndrome and paroxysmal atrial fibrillation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCRESAHA.107.168294"}], "href": "https://doi.org/10.1161/CIRCRESAHA.107.168294"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18451335"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18451335"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Arne Pfeufer, Charlotte van Noord, Kristin D Marciante, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association study of PR interval."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.517"}], "href": "https://doi.org/10.1038/ng.517"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20062060"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20062060"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Hilma Holm, Daniel F Gudbjartsson, David O Arnar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Several common variants modulate heart rate, PR interval and QRS duration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.511"}], "href": "https://doi.org/10.1038/ng.511"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20062063"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20062063"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Cornelis J J Boogerd, Dennis Dooijes, Aho Ilgun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional analysis of novel TBX5 T-box mutations associated with Holt-Oram syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cardiovasc Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/cvr/cvq178"}], "href": "https://doi.org/10.1093/cvr/cvq178"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20519243"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20519243"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "J Yu, X Ma, K F Cheung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epigenetic inactivation of T-box transcription factor 5, a novel tumor suppressor gene, is associated with colon cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2010.370"}], "href": "https://doi.org/10.1038/onc.2010.370"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20802524"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20802524"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Javier T Granados-Riveron, Mark Pope, Frances A Bu'lock, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Combined mutation screening of NKX2-5, GATA4, and TBX5 in congenital heart disease: multiple heterozygosity and novel mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Congenit Heart Dis (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1747-0803.2011.00573.x"}], "href": "https://doi.org/10.1111/j.1747-0803.2011.00573.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22011241"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22011241"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Chirag Patel, Lee Silcock, Dominic McMullan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TBX5 intragenic duplication: a family with an atypical Holt-Oram syndrome phenotype."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ejhg.2012.16"}], "href": "https://doi.org/10.1038/ejhg.2012.16"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22333898"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22333898"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Hanine Hajj, John M Dagle "}, {"type": "b", "children": [{"type": "t", "text": "Genetics of patent ductus arteriosus susceptibility and treatment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Semin Perinatol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1053/j.semperi.2011.09.019"}], "href": "https://doi.org/10.1053/j.semperi.2011.09.019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22414880"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22414880"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Scott Smemo, Luciene C Campos, Ivan P Moskowitz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulatory variation in a TBX5 enhancer leads to isolated congenital heart disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/dds165"}], "href": "https://doi.org/10.1093/hmg/dds165"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22543974"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22543974"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Joseph Rosenbluh, Deepak Nijhawan, Andrew G Cox, et al. "}, {"type": "b", "children": [{"type": "t", "text": "β-Catenin-driven cancers require a YAP1 transcriptional complex for survival and tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2012.11.026"}], "href": "https://doi.org/10.1016/j.cell.2012.11.026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23245941"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23245941"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Moritz F Sinner, Nathan R Tucker, Kathryn L Lunetta, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Integrating genetic, transcriptional, and functional analyses to identify 5 novel genes for atrial fibrillation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circulation (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCULATIONAHA.114.009892"}], "href": "https://doi.org/10.1161/CIRCULATIONAHA.114.009892"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25124494"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25124494"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Anwar Baban, Alex Vincent Postma, Monica Marini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of TBX5 mutations in a series of 94 patients with Tetralogy of Fallot."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.36783"}], "href": "https://doi.org/10.1002/ajmg.a.36783"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25263169"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25263169"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Alban-Elouen Baruteau, Vincent Probst, Hugues Abriel "}, {"type": "b", "children": [{"type": "t", "text": "Inherited progressive cardiac conduction disorders."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Opin Cardiol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/HCO.0000000000000134"}], "href": "https://doi.org/10.1097/HCO.0000000000000134"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25426816"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25426816"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Claire Palles, Laura Chegwidden, Xinzhong Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gastroenterology (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1053/j.gastro.2014.10.041"}], "href": "https://doi.org/10.1053/j.gastro.2014.10.041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25447851"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25447851"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Mohammad M Al-Qattan, Hussam Abou Al-Shaar "}, {"type": "b", "children": [{"type": "t", "text": "Molecular basis of the clinical features of Holt-Oram syndrome resulting from missense and extended protein mutations of the TBX5 gene as well as TBX5 intragenic duplications."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2015.02.017"}], "href": "https://doi.org/10.1016/j.gene.2015.02.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25680289"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25680289"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Xian-Ling Zhang, Xing-Biao Qiu, Fang Yuan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TBX5 loss-of-function mutation contributes to familial dilated cardiomyopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2015.02.094"}], "href": "https://doi.org/10.1016/j.bbrc.2015.02.094"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25725155"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25725155"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Wei Zhou, Lan Zhao, Jin-Qi Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel TBX5 loss-of-function mutation associated with sporadic dilated cardiomyopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Med (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijmm.2015.2206"}], "href": "https://doi.org/10.3892/ijmm.2015.2206"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25963046"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25963046"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Ji-Fang Ma, Fan Yang, Saagar N Mahida, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TBX5 mutations contribute to early-onset atrial fibrillation in Chinese and Caucasians."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cardiovasc Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/cvr/cvw003"}], "href": "https://doi.org/10.1093/cvr/cvw003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26762269"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26762269"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Jieyun Bai, Patrick A Gladding, Martin K Stiles, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ionic and cellular mechanisms underlying TBX5/PITX2 insufficiency-induced atrial fibrillation: Insights from mathematical models of human atrial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-018-33958-y"}], "href": "https://doi.org/10.1038/s41598-018-33958-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30353147"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30353147"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Eman G Behiry, Mahmoud A Al-Azzouny, Dina Sabry, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of NKX2-5, GATA4, and TBX5 polymorphisms with congenital heart disease in Egyptian children."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Genomic Med (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mgg3.612"}], "href": "https://doi.org/10.1002/mgg3.612"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30834692"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30834692"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Chun Fan, Qiuyun Chen, Qing Kenneth Wang "}, {"type": "b", "children": [{"type": "t", "text": "Functional role of transcriptional factor TBX5 in pre-mRNA splicing and Holt-Oram syndrome via association with SC35."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.041368"}], "href": "https://doi.org/10.1074/jbc.M109.041368"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19648116"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19648116"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Feng Wang, Xue-Yan Yang, Jian-Yuan Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-10a and miR-10b target the 3'-untranslated region of TBX5 to repress its expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pediatr Cardiol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00246-014-0901-y"}], "href": "https://doi.org/10.1007/s00246-014-0901-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24714979"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24714979"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Lauren Waldron, Jeffrey D Steimle, Todd M Greco, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Cardiac TBX5 Interactome Reveals a Chromatin Remodeling Network Essential for Cardiac Septation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2016.01.009"}], "href": "https://doi.org/10.1016/j.devcel.2016.01.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26859351"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26859351"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Yukiko Hata, Koshi Kinoshita, Koichi Mizumaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Postmortem genetic analysis of sudden unexplained death syndrome under 50 years of age: A next-generation sequencing study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Heart Rhythm (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.hrthm.2016.03.038"}], "href": "https://doi.org/10.1016/j.hrthm.2016.03.038"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27005929"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27005929"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Lin-Ting Hsia, Neil Ashley, Djamila Ouaret, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Myofibroblasts are distinguished from activated skin fibroblasts by the expression of AOC3 and other associated markers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1603534113"}], "href": "https://doi.org/10.1073/pnas.1603534113"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27036009"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27036009"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Athar Khalil, Rachel Tanos, Nehmé El-Hachem, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A HAND to TBX5 Explains the Link Between Thalidomide and Cardiac Diseases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-017-01641-3"}], "href": "https://doi.org/10.1038/s41598-017-01641-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28469241"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28469241"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Nazim Hussain, Wenhua Zhu, Congshan Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Down-regulation of miR-10a-5p in synoviocytes contributes to TBX5-controlled joint inflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.13312"}], "href": "https://doi.org/10.1111/jcmm.13312"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28782180"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28782180"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Irfan S Kathiriya, Kavitha S Rao, Giovanni Iacono, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Modeling Human TBX5 Haploinsufficiency Predicts Regulatory Networks for Congenital Heart Disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2020.11.020"}], "href": "https://doi.org/10.1016/j.devcel.2020.11.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33321106"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33321106"}]}]}]}