{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T17:49:53Z","timestamp":1783619393084,"version":"3.55.0"},"reference-count":73,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T00:00:00Z","timestamp":1740614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"T32 UCLA\u2019s Medical Genetics T32 Research Training Program","award":["NIH\/NIGMS T32GM008243"],"award-info":[{"award-number":["NIH\/NIGMS T32GM008243"]}]},{"name":"T32 UCLA\u2019s Medical Genetics T32 Research Training Program","award":["R25Actf HD109116Projectf01A1"],"award-info":[{"award-number":["R25Actf HD109116Projectf01A1"]}]},{"name":"T32 UCLA\u2019s Medical Genetics T32 Research Training Program","award":["1R01 HL153853-01"],"award-info":[{"award-number":["1R01 HL153853-01"]}]},{"name":"R25 Education Program in Bioinformatics, Omics, and Computational Biology NIH\/NICHHD","award":["NIH\/NIGMS T32GM008243"],"award-info":[{"award-number":["NIH\/NIGMS T32GM008243"]}]},{"name":"R25 Education Program in Bioinformatics, Omics, and Computational Biology NIH\/NICHHD","award":["R25Actf HD109116Projectf01A1"],"award-info":[{"award-number":["R25Actf HD109116Projectf01A1"]}]},{"name":"R25 Education Program in Bioinformatics, Omics, and Computational Biology NIH\/NICHHD","award":["1R01 HL153853-01"],"award-info":[{"award-number":["1R01 HL153853-01"]}]},{"name":"UCLA CDI","award":["NIH\/NIGMS T32GM008243"],"award-info":[{"award-number":["NIH\/NIGMS T32GM008243"]}]},{"name":"UCLA CDI","award":["R25Actf HD109116Projectf01A1"],"award-info":[{"award-number":["R25Actf HD109116Projectf01A1"]}]},{"name":"UCLA CDI","award":["1R01 HL153853-01"],"award-info":[{"award-number":["1R01 HL153853-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>One out of every hundred live births present with congenital heart abnormalities caused by the aberrant development of the embryonic cardiovascular system. The conserved zinc finger transcription factor proteins, which include GATA binding protein 5 (GATA5) and GATA binding protein (GATA6) play important roles in embryonic development and their inactivation may result in congenital heart defects (CHDs). In this study, we performed genotypic\u2013phenotypic analyses in two families affected by right-sided CHD diagnosed by echocardiography imaging. Proband A presented with pulmonary valve stenosis, and proband B presented with complex CHD involving the right heart structures. For variant detection, we employed whole-genome single-nucleotide polymorphism (SNP) microarray and family-based whole-exome sequencing (WES) studies. Proband A is a full-term infant who was admitted to the neonatal intensive care unit (NICU) at five days of life for pulmonary valve stenosis (PVS). Genomic studies revealed a normal SNP microarray; however, quad WES analysis identified a novel heterozygous [Chr20:g.61041597C&gt;G (p.Arg237Pro)] variant in the GATA5 gene. Further analysis confirmed that the novel variant was inherited from the mother but was absent in the father and the maternal uncle with a history of heart murmur. Proband B was born prematurely at 35 weeks gestation with a prenatally diagnosed complex CHD. A postnatal evaluation revealed right-sided heart defects including pulmonary atresia with intact ventricular septum (PA\/IVS), right ventricular hypoplasia, tricuspid valve hypoplasia, hypoplastic main and bilateral branch pulmonary arteries, and possible coronary sinusoids. Cardiac catheterization yielded anatomy and hemodynamics unfavorable to repair. Hence, heart transplantation was indicated. Upon genomic testing, a normal SNP microarray was observed, while trio WES analysis identified a novel heterozygous [Chr18:c.1757C&gt;T (p.Pro586Leu)] variant in the GATA6 gene. This variant was inherited from the father, who carries a clinical diagnosis of tetralogy of Fallot. These findings provide new insights into novel GATA5\/6 variants, elaborate on the genotypic and phenotypic association, and highlight the critical role of GATA5 and GATA6 transcription factors in a wide spectrum of right-sided CHDs.<\/jats:p>","DOI":"10.3390\/ijms26052115","type":"journal-article","created":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T08:04:44Z","timestamp":1740643484000},"page":"2115","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Whole-Exome Sequencing Identifies Novel GATA5\/6 Variants in Right-Sided Congenital Heart Defects"],"prefix":"10.3390","volume":"26","author":[{"given":"Gloria K. E.","family":"Zodanu","sequence":"first","affiliation":[{"name":"Neonatal Congenital Heart Laboratory, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"},{"name":"Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7350-407X","authenticated-orcid":false,"given":"John H.","family":"Hwang","sequence":"additional","affiliation":[{"name":"Neonatal Congenital Heart Laboratory, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"},{"name":"Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0438-8607","authenticated-orcid":false,"given":"Jordan","family":"Mudery","sequence":"additional","affiliation":[{"name":"Neonatal Congenital Heart Laboratory, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"},{"name":"Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3322-8434","authenticated-orcid":false,"given":"Carlos","family":"Sisniega","sequence":"additional","affiliation":[{"name":"Neonatal Congenital Heart Laboratory, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"},{"name":"Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuedong","family":"Kang","sequence":"additional","affiliation":[{"name":"Neonatal Congenital Heart Laboratory, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"},{"name":"Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7108-2897","authenticated-orcid":false,"given":"Lee-Kai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Barsegian","sequence":"additional","affiliation":[{"name":"Neonatal Congenital Heart Laboratory, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"},{"name":"Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2409-0907","authenticated-orcid":false,"given":"Reshma M.","family":"Biniwale","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"},{"name":"Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Sing","family":"Si","sequence":"additional","affiliation":[{"name":"Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy J.","family":"Halnon","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"UCLA Congenital Heart Defects-BioCore Faculty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne W.","family":"Grody","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"},{"name":"Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"},{"name":"Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary M.","family":"Satou","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glen S.","family":"Van Arsdell","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"},{"name":"Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanly F.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"},{"name":"Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"},{"name":"Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2827-4068","authenticated-orcid":false,"given":"Marlin","family":"Touma","sequence":"additional","affiliation":[{"name":"Neonatal Congenital Heart Laboratory, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"},{"name":"Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"},{"name":"Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA"},{"name":"Children\u2019s Discovery and Innovation Institute, University of California, Los Angeles, CA 90095, USA"},{"name":"Eli and Edyth Broad Stem Cell Research Center, University of California, Los Angeles, CA 90095, USA"},{"name":"Cardiovascular Research Laboratories, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S1462399406000093","article-title":"GATA factors in vertebrate heart development and disease","volume":"8","author":"Brewer","year":"2006","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_2","first-page":"1065","article-title":"A novel GATA6 mutation associated with congenital ventricular septal defect","volume":"29","author":"Liu","year":"2012","journal-title":"Int. J. Mol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.ydbio.2008.11.004","article-title":"Interaction of Gata4 and Gata6 with Tbx5 is critical for normal cardiac development","volume":"326","author":"Maitra","year":"2009","journal-title":"Dev. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1161\/CIRCRESAHA.112.300853","article-title":"Genetics of Congenital Heart Disease: The Glass Half Empty","volume":"112","author":"Fahed","year":"2013","journal-title":"Circ. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.aanat.2005.10.007","article-title":"Bridging the gap between anatomy and molecular genetics for an improved understanding of congenital heart disease","volume":"188","author":"Borlak","year":"2006","journal-title":"Ann. Anat.-Anat. Anz."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"El-Assaad, A., Dawy, Z., Khalil, A., and Nemer, G. (2021). Mutational signatures in GATA3 transcription factor and its DNA binding domain that stimulate breast cancer and HDR syndrome. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-01832-z"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Afouda, B.A. (2022). Towards Understanding the Gene-Specific Roles of GATA Factors in Heart Development: Does GATA4 Lead the Way?. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23095255"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.sbi.2004.05.004","article-title":"Structure and evolution of transcriptional regulatory networks","volume":"14","author":"Babu","year":"2004","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1002\/j.1939-4640.2004.tb02813.x","article-title":"The 25th Volume: Role of the GATA Family of Transcription Factors in Andrology","volume":"25","author":"Viger","year":"2004","journal-title":"J. Androl."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1093\/nar\/gkg161","article-title":"Structural classification of zinc fingers: SURVEY AND SUMMARY","volume":"31","author":"Krishna","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Li, X., Han, M., Zhang, H., Liu, F., Pan, Y., Zhu, J., Liao, Z., Chen, X., and Zhang, B. (2022). Structures and biological functions of zinc finger proteins and their roles in hepatocellular carcinoma. Biomark. Res., 10.","DOI":"10.1186\/s40364-021-00345-1"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/B978-0-12-387786-4.00008-7","article-title":"Transcription Factor Pathways and Congenital Heart Disease","volume":"100","author":"McCulley","year":"2012","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1016\/j.jmb.2008.06.072","article-title":"Crystal Structures of Multiple GATA Zinc Fingers Bound to DNA Reveal New Insights into DNA Recognition and Self-Association by GATA","volume":"381","author":"Bates","year":"2008","journal-title":"J. Mol. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"dev164384","DOI":"10.1242\/dev.164384","article-title":"GATA transcription factors in development and disease","volume":"145","author":"Tremblay","year":"2018","journal-title":"Development"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1089\/dna.2012.1814","article-title":"Novel GATA6 Mutations Associated with Congenital Ventricular Septal Defect or Tetralogy of Fallot","volume":"31","author":"Wang","year":"2012","journal-title":"DNA Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1002\/ajmg.a.61294","article-title":"GATA6 mutations: Characterization of two novel patients and a comprehensive overview of the GATA6 genotypic and phenotypic spectrum","volume":"179","author":"Tjong","year":"2019","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.3892\/ijmm.2014.1896","article-title":"GATA6 loss-of-function mutations contribute to familial dilated cardiomyopathy","volume":"34","author":"Xu","year":"2014","journal-title":"Int. J. Mol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1177\/153537020322801107","article-title":"The Role of GATA in Mammalian Reproduction","volume":"228","author":"LaVoie","year":"2003","journal-title":"Exp. Biol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1002\/(SICI)1520-6408(1998)22:3<263::AID-DVG8>3.0.CO;2-4","article-title":"Common role for each of the cGATA-4\/5\/6 genes in the regulation of cardiac morphogenesis","volume":"22","author":"Jiang","year":"1998","journal-title":"Dev. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1038\/jhg.2010.84","article-title":"A novel GATA6 mutation in patients with tetralogy of Fallot or atrial septal defect","volume":"55","author":"Lin","year":"2010","journal-title":"J. Hum. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e3","DOI":"10.1017\/erm.2016.2","article-title":"The emerging role of GATA transcription factors in development and disease","volume":"18","author":"Lentjes","year":"2016","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.ydbio.2011.07.037","article-title":"GATA5 interacts with GATA4 and GATA6 in outflow tract development","volume":"358","author":"Laforest","year":"2011","journal-title":"Dev. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.cardiores.2004.03.025","article-title":"GATA transcription factors in the developing and adult heart","volume":"63","author":"Pikkarainen","year":"2004","journal-title":"Cardiovasc. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"G474","DOI":"10.1152\/ajpgi.00119.2013","article-title":"Role of GATA factors in development, differentiation, and homeostasis of the small intestinal epithelium","volume":"306","author":"Aronson","year":"2014","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s002399910012","article-title":"Molecular Evolution of the GATA Family of Transcription Factors: Conservation Within the DNA-Binding Domain","volume":"50","author":"Lowry","year":"2000","journal-title":"J. Mol. Evol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1002\/iub.2163","article-title":"From embryogenesis to adulthood: Critical role for GATA factors in heart development and function","volume":"72","author":"Whitcomb","year":"2020","journal-title":"IUBMB Life"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.mce.2015.05.027","article-title":"GATA factors in endocrine neoplasia","volume":"421","author":"Pihlajoki","year":"2016","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1097\/MOP.0b013e328013e7b2","article-title":"Molecular insights into Down syndrome-associated leukemia","volume":"19","author":"Vyas","year":"2007","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"266","DOI":"10.4103\/apc.apc_63_23","article-title":"In silico prediction, molecular modeling, and dynamics studies on the targeted next-generation sequencing identified genes underlying congenital heart disease in Down syndrome patients","volume":"16","author":"Carlus","year":"2023","journal-title":"Ann. Pediatr. Cardiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"287","DOI":"10.5830\/CVJA-2016-019","article-title":"Congenital heart disease and Down syndrome: Various aspects of a confirmed association","volume":"27","author":"Benhaourech","year":"2016","journal-title":"Cardiovasc. J. Afr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1101\/gr.147991.112","article-title":"The complex SNP and CNV genetic architecture of the increased risk of congenital heart defects in Down syndrome","volume":"23","author":"Sailani","year":"2013","journal-title":"Genome Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.semcdb.2004.10.003","article-title":"The roles of GATA-4, -5 and -6 in vertebrate heart development","volume":"16","author":"Peterkin","year":"2005","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"34","DOI":"10.7150\/ijms.5270","article-title":"GATA5 loss-of-Function Mutations Underlie Tetralogy of Fallot","volume":"10","author":"Wei","year":"2013","journal-title":"Int. J. Med Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1007\/s00246-012-0482-6","article-title":"GATA5 Loss-of-Function Mutation Responsible for the Congenital Ventriculoseptal Defect","volume":"34","author":"Wei","year":"2013","journal-title":"Pediatr. Cardiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/mgg3.190","article-title":"GATA5 mutation homozygosity linked to a double outlet right ventricle phenotype in a Lebanese patient","volume":"4","author":"Kassab","year":"2016","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1172\/JCI27363","article-title":"GATA-6 regulates semaphorin 3C and is required in cardiac neural crest for cardiovascular morphogenesis","volume":"116","author":"Lepore","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1006\/geno.1996.0630","article-title":"The HumanGATA-6Gene: Structure, Chromosomal Location, and Regulation of Expression by Tissue-Specific and Mitogen-Responsive Signals","volume":"38","author":"Suzukia","year":"1996","journal-title":"Genomics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1203\/PDR.0b013e3181ed17e4","article-title":"Identification of GATA6 Sequence Variants in Patients With Congenital Heart Defects","volume":"68","author":"Maitra","year":"2010","journal-title":"Pediatr. Res."},{"key":"ref_39","first-page":"11.10.1","article-title":"From FastQ Data to High-Confidence Variant Calls: The Genome Analysis Toolkit Best Practices Pipeline","volume":"43","author":"Carneiro","year":"2013","journal-title":"Curr. Protoc. Bioinform."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"961","DOI":"10.21037\/atm-21-1635","article-title":"Rare variants: Data types and analysis strategies","volume":"9","author":"Goswami","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Robinson, J.T., Thorvaldsdottir, H., Turner, D., and Mesirov, J.P. (2023). igv.js: An embeddable JavaScript implementation of the Integrative Genomics Viewer (IGV). Bioinformatics, 39.","DOI":"10.1093\/bioinformatics\/btac830"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"253","DOI":"10.31083\/j.rcm.2020.02.5104","article-title":"Potential roles of GATA binding protein 5 in cardiovascular diseases","volume":"21","author":"Song","year":"2020","journal-title":"Rev. Cardiovasc. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.6061\/clinics\/2012(12)08","article-title":"Novel GATA5 loss-of-function mutations underlie familial atrial fibrillation","volume":"67","author":"Gu","year":"2012","journal-title":"Clinics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"763","DOI":"10.3892\/ijmm.2014.2050","article-title":"GATA5 loss-of-function mutation in familial dilated cardiomyopathy","volume":"35","author":"Zhang","year":"2015","journal-title":"Int. J. Mol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"654","DOI":"10.3892\/ijmm.2013.1600","article-title":"A novel GATA4 loss-of-function mutation responsible for familial dilated cardiomyopathy","volume":"33","author":"Zhao","year":"2014","journal-title":"Int. J. Mol. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.yjmcc.2012.05.009","article-title":"Rare non-synonymous variations in the transcriptional activation domains of GATA5 in bicuspid aortic valve disease","volume":"53","author":"Padang","year":"2012","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.ijcard.2012.03.132","article-title":"Mutational spectrum of the GATA5 gene associated with familial atrial fibrillation","volume":"157","author":"Yang","year":"2012","journal-title":"Int. J. Cardiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1007\/s12519-014-0511-z","article-title":"Novel and functional DNA sequence variants within the GATA5 gene promoter in ventricular septal defects","volume":"10","author":"Shan","year":"2014","journal-title":"World J. Pediatr."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kalisch-Smith, J.I., Ved, N., and Sparrow, D.B. (2020). Environmental Risk Factors for Congenital Heart Disease. Cold Spring Harb. Perspect. Biol., 12.","DOI":"10.1101\/cshperspect.a037234"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/pr.2014.67","article-title":"Rare GATA5 sequence variants identified in individuals with bicuspid aortic valve","volume":"76","author":"Bonachea","year":"2014","journal-title":"Pediatr. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.3892\/ijmm.2014.1700","article-title":"GATA5 loss-of-function mutations associated with congenital bicuspid aortic valve","volume":"33","author":"Shi","year":"2014","journal-title":"Int. J. Mol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s11886-014-0487-2","article-title":"Genetics of Valvular Heart Disease","volume":"16","author":"LaHaye","year":"2014","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_54","first-page":"414","article-title":"Pulmonary valve stenosis in the adult patient: Pathophysiology, diagnosis and management","volume":"105","author":"Ruckdeschel","year":"2018","journal-title":"Heart"},{"key":"ref_55","first-page":"785","article-title":"Identification of two novel GATA6 mutations in an adult with acute myocardial infarction, diabetes, and atrial fibrillation: A case report","volume":"16","author":"Sun","year":"2019","journal-title":"J. Geriatr. Cardiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"11189","DOI":"10.1073\/pnas.0604604103","article-title":"A threshold of GATA4 and GATA6 expression is required for cardiovascular development","volume":"103","author":"Xin","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1161\/CIRCULATIONAHA.117.029506","article-title":"GATA6 Regulates Aortic Valve Remodeling, and Its Haploinsufficiency Leads to Right-Left Type Bicuspid Aortic Valve","volume":"138","author":"Gharibeh","year":"2018","journal-title":"Circulation"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/s10038-021-00976-0","article-title":"Rare GATA6 variants associated with risk of congenital heart disease phenotypes in 200,000 UK Biobank exomes","volume":"67","author":"Williams","year":"2022","journal-title":"J. Hum. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.hrthm.2016.10.014","article-title":"Gain-of-function mutations in GATA6 lead to atrial fibrillation","volume":"14","author":"Tucker","year":"2017","journal-title":"Hear. Rhythm."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1038\/s41390-023-02811-y","article-title":"Novel pathogenic GATA6 variant associated with congenital heart disease, diabetes mellitus and necrotizing enterocolitis","volume":"95","author":"Yasuhara","year":"2024","journal-title":"Pediatr. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4745","DOI":"10.1074\/jbc.M411585200","article-title":"GATA-6 Can Act as a Positive or Negative Regulator of Smooth Muscle-specific Gene Expression","volume":"280","author":"Yin","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"13933","DOI":"10.1073\/pnas.0904744106","article-title":"GATA6 mutations cause human cardiac outflow tract defects by disrupting semaphorin-plexin signaling","volume":"106","author":"Kodo","year":"2009","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.gene.2017.10.083","article-title":"Targeted sequencing identifies novel GATA6 variants in a large cohort of patients with conotruncal heart defects","volume":"641","author":"Zhang","year":"2018","journal-title":"Gene"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"The International Pancreatic Agenesis Consortium, Allen, H.L., Flanagan, S.E., Shaw-Smith, C., De Franco, E., Akerman, I., Caswell, R., Ferrer, J., Hattersley, A.T., and Ellard, S. (2012). GATA6 haploinsufficiency causes pancreatic agenesis in humans. Nat. Genet., 44, 20\u201322.","DOI":"10.1038\/ng.1035"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1136\/jmedgenet-2013-101989","article-title":"Whole exome sequencing identifies de novo mutations in GATA6 associated with congenital diaphragmatic hernia","volume":"51","author":"Yu","year":"2014","journal-title":"J. Med. Genet."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.bbrc.2022.12.004","article-title":"Functional characterization of GATA6 genetic variants associated with mild congenital heart defects","volume":"641","author":"Wu","year":"2023","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.recesp.2018.06.020","article-title":"MicroRNAs and Congenital Heart Disease: Where Are We Now?","volume":"72","author":"Pulignani","year":"2019","journal-title":"Rev. Esp. Cardiol. Engl. Ed."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.5114\/aoms\/169775","article-title":"Cardiac microRNAs: Diagnostic and therapeutic potential","volume":"19","author":"Badacz","year":"2023","journal-title":"Arch. Med. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Yan, S., and Jiao, K. (2016). Functions of miRNAs during Mammalian Heart Development. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17050789"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.scr.2013.11.009","article-title":"miR-200c and GATA binding protein 4 regulate human embryonic stem cell renewal and differentiation","volume":"12","author":"Huang","year":"2014","journal-title":"Stem Cell Res."},{"key":"ref_71","first-page":"1","article-title":"Role of Epigenetics in Cardiac Development and Cardiovascular Diseases","volume":"3","author":"Dong","year":"2017","journal-title":"J. Hear. Health"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Liu, J.-J., Zhao, C.-M., Li, Z.-G., Wang, Y.-M., Miao, W., Wu, X.-J., Wang, W.-J., Liu, C., Wang, D., and Wang, K. (2016). miR-218 Involvement in Cardiomyocyte Hypertrophy Is Likely through Targeting REST. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17060848"},{"key":"ref_73","first-page":"CD011912","article-title":"Pulse oximetry screening for critical congenital heart defects","volume":"2018","author":"Plana","year":"2018","journal-title":"Cochrane Database Syst. Rev."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/5\/2115\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:43:33Z","timestamp":1760028213000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/5\/2115"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,27]]},"references-count":73,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["ijms26052115"],"URL":"https:\/\/doi.org\/10.3390\/ijms26052115","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,27]]}}}