{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T04:04:05Z","timestamp":1783051445290,"version":"3.54.6"},"reference-count":136,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004704","name":"National Research Council of Thailand","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Chiang Mai University Center of Excellence"},{"DOI":"10.13039\/501100002842","name":"Chiang Mai University","doi-asserted-by":"crossref","award":["(CMU-2568)"],"award-info":[{"award-number":["(CMU-2568)"]}],"id":[{"id":"10.13039\/501100002842","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Congenital heart disease (CHD) is the most common congenital anomaly worldwide and poses significant diagnostic challenges due to its structural complexity and frequent association with extracardiac anomalies and genetic abnormalities. While conventional tests such as karyotyping, quantitative fluorescent polymerase chain reaction (QF-PCR), and chromosomal microarray analysis (CMA) are standard first-tier investigations, many cases remain genetically unexplained. Prenatal whole exome sequencing (WES) has emerged as a valuable tool to detect pathogenic single gene variants underlying CHD. This narrative review synthesizes findings from 28 studies involving over 2000 WES-tested fetuses and more than 10,000 CHD cases. The additional diagnostic yield of WES over CMA ranged from 8.0% to 66.7%, with higher yields in syndromic or non-isolated CHD (10\u201350%) compared to isolated cases (7.1\u201327.8%). Trio-based WES outperformed proband-only sequencing by improving accuracy, reducing turnaround time, and lowering the rate of variant of uncertain significance (VUS). Prenatal WES not only clarifies genetic etiology but also reveals syndromic diagnoses, allowing CHD to be interpreted within broader multisystem contexts. Integration of phenotypic and genomic data enhances prenatal counseling, prognostication, delivery planning, and postnatal care\u2014advancing precision medicine in fetal cardiology.<\/jats:p>","DOI":"10.3390\/ijms27041720","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T17:10:52Z","timestamp":1770743452000},"page":"1720","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Application of Prenatal Whole Exome Sequencing for Congenital Heart Anomalies"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7204-1387","authenticated-orcid":false,"given":"Threebhorn","family":"Kamlungkuea","sequence":"first","affiliation":[{"name":"Fetal Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Department of Obstetrics and Gynecology, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7152-1952","authenticated-orcid":false,"given":"Fuanglada","family":"Tongprasert","sequence":"additional","affiliation":[{"name":"Fetal Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Department of Obstetrics and Gynecology, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2329-2176","authenticated-orcid":false,"given":"Duangrurdee","family":"Wattanasirichaigoon","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6376-2967","authenticated-orcid":false,"given":"Sirinart","family":"Kumfu","sequence":"additional","affiliation":[{"name":"Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Center of Excellence in Cardiac Electrophysiology Research, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1677-7052","authenticated-orcid":false,"given":"Siriporn C.","family":"Chattipakorn","sequence":"additional","affiliation":[{"name":"Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Center of Excellence in Cardiac Electrophysiology Research, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3026-718X","authenticated-orcid":false,"given":"Nipon","family":"Chattipakorn","sequence":"additional","affiliation":[{"name":"Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Center of Excellence in Cardiac Electrophysiology Research, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3389-6478","authenticated-orcid":false,"given":"Theera","family":"Tongsong","sequence":"additional","affiliation":[{"name":"Fetal Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1093\/ije\/dyz009","article-title":"Global birth prevalence of congenital heart defects 1970\u20132017: Updated systematic review and meta-analysis of 260 studies","volume":"48","author":"Liu","year":"2019","journal-title":"Int. J. Epidemiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/S2352-4642(19)30402-X","article-title":"Global, regional, and national burden of congenital heart disease, 1990\u20132017: A systematic analysis for the Global Burden of Disease Study 2017","volume":"4","author":"Zimmerman","year":"2020","journal-title":"Lancet Child. Adolesc. Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1016\/S0735-1097(02)01886-7","article-title":"The incidence of congenital heart disease","volume":"39","author":"Hoffman","year":"2002","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s00246-023-03308-5","article-title":"Outcomes and Associated Extracardiac Malformations in Neonates from Colombia with Severe Congenital Heart Disease","volume":"45","author":"Alvarado","year":"2024","journal-title":"Pediatr. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.pcl.2020.06.009","article-title":"Outcomes in Adult Congenital Heart Disease: Neurocognitive Issues and Transition of Care","volume":"67","author":"Jacobsen","year":"2020","journal-title":"Pediatr. Clin. N. Am."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/s41390-023-02490-9","article-title":"Critical congenital heart disease beyond HLHS and TGA: Neonatal brain injury and early neurodevelopment","volume":"94","author":"Vassar","year":"2023","journal-title":"Pediatr. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e028139","DOI":"10.1136\/bmjopen-2018-028139","article-title":"Prenatal diagnosis and prevalence of critical congenital heart defects: An international retrospective cohort study","volume":"9","author":"Bakker","year":"2019","journal-title":"BMJ Open"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1002\/uog.2710","article-title":"Prenatal detection of heart defects in a non-selected population of 30,149 fetuses--detection rates and outcome","volume":"27","author":"Tegnander","year":"2006","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"American Institute of Ultrasound in Medicine (2020). AIUM Practice Parameter for the Performance of Fetal Echocardiography. J. Ultrasound Med., 39, e5\u2013e16.","DOI":"10.1002\/jum.15263"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1161\/01.cir.0000437597.44550.5d","article-title":"Diagnosis and treatment of fetal cardiac disease: A scientific statement from the American Heart Association","volume":"129","author":"Donofrio","year":"2014","journal-title":"Circulation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2995","DOI":"10.1161\/CIRCULATIONAHA.106.183216","article-title":"Noninherited risk factors and congenital cardiovascular defects: Current knowledge: A scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young: Endorsed by the American Academy of Pediatrics","volume":"115","author":"Jenkins","year":"2007","journal-title":"Circulation"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1002\/pd.6597","article-title":"Is there an increased risk of genetic abnormalities in fetuses with congenital heart disease in the setting of growth restriction?","volume":"44","author":"Gianforcaro","year":"2024","journal-title":"Prenat. Diagn."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.21037\/tp-21-297","article-title":"Genetics of congenital heart disease: A narrative review of recent advances and clinical implications","volume":"10","author":"Yasuhara","year":"2021","journal-title":"Transl. Pediatr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1590\/0103-0582201432213213","article-title":"Congenital heart disease and chromossomopathies detected by the karyotype","volume":"32","author":"Trevisan","year":"2014","journal-title":"Rev. Paul. Pediatr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1007\/s00404-023-06910-3","article-title":"Chromosomal abnormalities in fetuses with congenital heart disease: A meta-analysis","volume":"308","author":"Wang","year":"2023","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"101986","DOI":"10.1016\/j.gde.2022.101986","article-title":"Copy-number variation in congenital heart disease","volume":"77","author":"Ehrlich","year":"2022","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1002\/pd.5212","article-title":"ACOG and SMFM guidelines for prenatal diagnosis: Is karyotyping really sufficient?","volume":"38","author":"Hay","year":"2018","journal-title":"Prenat. Diagn."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/uog.22072","article-title":"COngenital heart disease and the Diagnostic yield with Exome sequencing (CODE) study: Prospective cohort study and systematic review","volume":"57","author":"Mone","year":"2021","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1002\/pd.6581","article-title":"The incremental yield of prenatal exome sequencing over chromosome microarray for congenital heart abnormalities: A systematic review and meta-analysis","volume":"44","author":"Reilly","year":"2024","journal-title":"Prenat. Diagn."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"(2016). Committee Opinion No.682: Microarrays and Next-Generation Sequencing Technology: The Use of Advanced Genetic Diagnostic Tools in Obstetrics and Gynecology. Obstet. Gynecol., 128, e262\u2013e268.","DOI":"10.1097\/AOG.0000000000001817"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.gim.2021.09.016","article-title":"Implementation of fetal clinical exome sequencing: Comparing prospective and retrospective cohorts","volume":"24","author":"Marangoni","year":"2022","journal-title":"Genet. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"16266","DOI":"10.1038\/s41598-024-67164-w","article-title":"Prenatal genetic diagnosis of fetuses with dextrocardia using whole exome sequencing in a tertiary center","volume":"14","author":"Xue","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"100866","DOI":"10.1016\/j.gim.2023.100866","article-title":"ACMG SF v3.2 list for reporting of secondary findings in clinical exome and genome sequencing: A policy statement of the American College of Medical Genetics and Genomics (ACMG)","volume":"25","author":"Miller","year":"2023","journal-title":"Genet. Med."},{"key":"ref_24","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_25","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1038\/s41436-019-0499-9","article-title":"From diagnostic yield to clinical impact: A pilot study on the implementation of prenatal exome sequencing in routine care","volume":"21","author":"Haak","year":"2019","journal-title":"Genet. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1056\/NEJMra1003941","article-title":"Franklin H. Epstein Lecture. Cardiac development and implications for heart disease","volume":"363","author":"Epstein","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/wdev.68","article-title":"Organogenesis of the vertebrate heart","volume":"2","author":"Miquerol","year":"2013","journal-title":"Wiley Interdiscip. Rev. Dev. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/j.cell.2006.09.003","article-title":"Making or breaking the heart: From lineage determination to morphogenesis","volume":"126","author":"Srivastava","year":"2006","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Maleki, S., Poujade, F.A., Bergman, O., G\u00e5din, J.R., Simon, N., L\u00e5ng, K., Franco-Cereceda, A., Body, S.C., Bj\u00f6rck, H.M., and Eriksson, P. (2019). Endothelial\/Epithelial Mesenchymal Transition in Ascending Aortas of Patients With Bicuspid Aortic Valve. Front. Cardiovasc. Med., 6.","DOI":"10.3389\/fcvm.2019.00182"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s11010-019-03618-4","article-title":"Differential expression of novel MicroRNAs from developing fetal heart of Gallus gallus domesticus implies a role in cardiac development","volume":"462","author":"Saxena","year":"2019","journal-title":"Mol. Cell Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1006\/dbio.2001.0283","article-title":"Tbx1, a DiGeorge syndrome candidate gene, is regulated by sonic hedgehog during pharyngeal arch development","volume":"235","author":"Garg","year":"2001","journal-title":"Dev. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/s41525-023-00363-y","article-title":"Chromatin regulators in the TBX1 network confer risk for conotruncal heart defects in 22q11.2DS","volume":"8","author":"Zhao","year":"2023","journal-title":"NPJ Genom. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/81695","article-title":"Loss-of-function mutations in the EGF-CFC gene CFC1 are associated with human left-right laterality defects","volume":"26","author":"Bamford","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1038\/ng1446","article-title":"Cited2 controls left-right patterning and heart development through a Nodal-Pitx2c pathway","volume":"36","author":"Bamforth","year":"2004","journal-title":"Nat. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1006\/dbio.2000.9739","article-title":"Regulation of gut and heart left-right asymmetry by context-dependent interactions between xenopus lefty and BMP4 signaling","volume":"223","author":"Branford","year":"2000","journal-title":"Dev. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.modgep.2006.01.010","article-title":"Localization of Brachyury (T) in embryonic and extraembryonic tissues during mouse gastrulation","volume":"6","author":"Inman","year":"2006","journal-title":"Gene Expr. Patterns"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1161\/CIRCRESAHA.110.227058","article-title":"Mesp1: A key regulator of cardiovascular lineage commitment","volume":"107","author":"Bondue","year":"2010","journal-title":"Circ. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.stem.2013.03.004","article-title":"Mesp1 patterns mesoderm into cardiac, hematopoietic, or skeletal myogenic progenitors in a context-dependent manner","volume":"12","author":"Chan","year":"2013","journal-title":"Cell Stem Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/ncb3024","article-title":"Early lineage restriction in temporally distinct populations of Mesp1 progenitors during mammalian heart development","volume":"16","author":"Lescroart","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1083\/jcb.201505082","article-title":"Mesp1 controls the speed, polarity, and directionality of cardiovascular progenitor migration","volume":"213","author":"Chiapparo","year":"2016","journal-title":"J. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.ydbio.2014.02.023","article-title":"Mesodermal Nkx2.5 is necessary and sufficient for early second heart field development","volume":"390","author":"Zhang","year":"2014","journal-title":"Dev. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5687","DOI":"10.1093\/emboj\/16.18.5687","article-title":"The cardiac transcription factors Nkx2-5 and GATA-4 are mutual cofactors","volume":"16","author":"Durocher","year":"1997","journal-title":"EMBO J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"42252","DOI":"10.1074\/jbc.M107814200","article-title":"Nkx2-5 activity is essential for cardiomyogenesis","volume":"276","author":"Jamali","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1242\/dev.126.6.1269","article-title":"The cardiac homeobox gene Csx\/Nkx2.5 lies genetically upstream of multiple genes essential for heart development","volume":"126","author":"Tanaka","year":"1999","journal-title":"Development"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/S1534-5807(03)00363-0","article-title":"Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart","volume":"5","author":"Cai","year":"2003","journal-title":"Dev. Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.ydbio.2009.11.006","article-title":"BMP signaling coordinates gene expression and cell migration during precardiac mesoderm development","volume":"340","author":"Christiaen","year":"2010","journal-title":"Dev. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/S0925-4773(99)00311-1","article-title":"BMP2 is required for early heart development during a distinct time period","volume":"91","author":"Schlange","year":"2000","journal-title":"Mech. Dev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.ydbio.2018.12.002","article-title":"Cardiovascular development and survival require Mef2c function in the myocardial but not the endothelial lineage","volume":"445","author":"Materna","year":"2019","journal-title":"Dev. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4315","DOI":"10.1242\/jcs.03186","article-title":"Disruption of MEF2 activity in cardiomyoblasts inhibits cardiomyogenesis","volume":"119","author":"Karamboulas","year":"2006","journal-title":"J. Cell Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.ydbio.2012.06.019","article-title":"Zebrafish Mef2ca and Mef2cb are essential for both first and second heart field cardiomyocyte differentiation","volume":"369","author":"Hinits","year":"2012","journal-title":"Dev. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3809","DOI":"10.1002\/dvdy.21803","article-title":"Cooperative interaction of Nkx2.5 and Mef2c transcription factors during heart development","volume":"237","author":"Vincentz","year":"2008","journal-title":"Dev. Dyn."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.1242\/dev.02408","article-title":"Fgf8 is required for anterior heart field development","volume":"133","author":"Ilagan","year":"2006","journal-title":"Development"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1242\/dev.129.8.1935","article-title":"Regulation of avian cardiogenesis by Fgf8 signaling","volume":"129","author":"Alsan","year":"2002","journal-title":"Development"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1242\/dev.127.2.225","article-title":"Induction and differentiation of the zebrafish heart requires fibroblast growth factor 8 (fgf8\/acerebellar)","volume":"127","author":"Reifers","year":"2000","journal-title":"Development"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.bbamcr.2008.08.013","article-title":"WNT signaling promotes Nkx2.5 expression and early cardiomyogenesis via downregulation of Hdac1","volume":"1793","author":"Liu","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"aaa6071","DOI":"10.1126\/science.aaa6071","article-title":"HEART DEVELOPMENT. Integration of Bmp and Wnt signaling by Hopx specifies commitment of cardiomyoblasts","volume":"348","author":"Jain","year":"2015","journal-title":"Science"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5834","DOI":"10.1073\/pnas.0935626100","article-title":"A Wnt- and beta -catenin-dependent pathway for mammalian cardiac myogenesis","volume":"100","author":"Nakamura","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"18531","DOI":"10.1073\/pnas.0703113104","article-title":"Distinct roles of Wnt\/beta-catenin and Bmp signaling during early cardiogenesis","volume":"104","author":"Klaus","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1101\/gad.855501","article-title":"Inhibition of Wnt activity induces heart formation from posterior mesoderm","volume":"15","author":"Marvin","year":"2001","journal-title":"Genes. Dev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.devcel.2004.07.023","article-title":"Foxh1 is essential for development of the anterior heart field","volume":"7","author":"Silvestri","year":"2004","journal-title":"Dev. Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3015","DOI":"10.1242\/dev.02470","article-title":"Conserved regulation and role of Pitx2 in situs-specific morphogenesis of visceral organs","volume":"133","author":"Shiratori","year":"2006","journal-title":"Development"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/S0092-8674(00)81472-5","article-title":"lefty-1 is required for left-right determination as a regulator of lefty-2 and nodal","volume":"94","author":"Meno","year":"1998","journal-title":"Cell"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"150187","DOI":"10.1098\/rsob.150187","article-title":"Nodal signalling in Xenopus: The role of Xnr5 in left\/right asymmetry and heart development","volume":"6","author":"Tadjuidje","year":"2016","journal-title":"Open Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1242\/dev.126.6.1225","article-title":"The homeobox gene Pitx2: Mediator of asymmetric left-right signaling in vertebrate heart and gut looping","volume":"126","author":"Campione","year":"1999","journal-title":"Development"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0092-8674(00)81474-9","article-title":"The transcription factor Pitx2 mediates situs-specific morphogenesis in response to left-right asymmetric signals","volume":"94","author":"Logan","year":"1998","journal-title":"Cell"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/S0012-1606(03)00389-0","article-title":"Pitx2c attenuation results in cardiac defects and abnormalities of intestinal orientation in developing Xenopus laevis","volume":"262","author":"Dagle","year":"2003","journal-title":"Dev. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1242\/dev.128.6.1005","article-title":"Differential expression and functional analysis of Pitx2 isoforms in regulation of heart looping in the chick","volume":"128","author":"Yu","year":"2001","journal-title":"Development"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.ydbio.2006.06.009","article-title":"Pitx2 regulates cardiac left-right asymmetry by patterning second cardiac lineage-derived myocardium","volume":"296","author":"Ai","year":"2006","journal-title":"Dev. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5025","DOI":"10.1093\/hmg\/ddu215","article-title":"Disruption of myocardial Gata4 and Tbx5 results in defects in cardiomyocyte proliferation and atrioventricular septation","volume":"23","author":"Misra","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.devcel.2012.06.006","article-title":"Tbx5-hedgehog molecular networks are essential in the second heart field for atrial septation","volume":"23","author":"Xie","year":"2012","journal-title":"Dev. Cell"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"19356","DOI":"10.1073\/pnas.0914888107","article-title":"An endocardial pathway involving Tbx5, Gata4, and Nos3 required for atrial septum formation","volume":"107","author":"Nadeau","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1093\/hmg\/ddv636","article-title":"Gene network and familial analyses uncover a gene network involving Tbx5\/Osr1\/Pcsk6 interaction in the second heart field for atrial septation","volume":"25","author":"Zhang","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"8231","DOI":"10.1074\/jbc.274.12.8231","article-title":"Context-dependent transcriptional cooperation mediated by cardiac transcription factors Csx\/Nkx-2.5 and GATA-4","volume":"274","author":"Shiojima","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1007\/s00018-011-0884-2","article-title":"Tbx2 and Tbx3 induce atrioventricular myocardial development and endocardial cushion formation","volume":"69","author":"Singh","year":"2012","journal-title":"Cell Mol. Life Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1161\/CIRCRESAHA.109.196063","article-title":"Tbx20 interacts with smads to confine tbx2 expression to the atrioventricular canal","volume":"105","author":"Singh","year":"2009","journal-title":"Circ. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/s41586-018-0110-6","article-title":"Control of cardiac jelly dynamics by NOTCH1 and NRG1 defines the building plan for trabeculation","volume":"557","author":"Ramialison","year":"2018","journal-title":"Nature"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"4627","DOI":"10.1128\/MCB.24.11.4627-4635.2004","article-title":"Role of Hand1\/eHAND in the dorso-ventral patterning and interventricular septum formation in the embryonic heart","volume":"24","author":"Togi","year":"2004","journal-title":"Mol. Cell Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/ng0697-154","article-title":"Regulation of cardiac mesodermal and neural crest development by the bHLH transcription factor, dHAND","volume":"16","author":"Srivastava","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"18604","DOI":"10.1073\/pnas.0900635106","article-title":"T-box 2, a mediator of Bmp-Smad signaling, induced hyaluronan synthase 2 and Tgfbeta2 expression and endocardial cushion formation","volume":"106","author":"Shirai","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3607","DOI":"10.1242\/dev.02519","article-title":"Development of heart valves requires Gata4 expression in endothelial-derived cells","volume":"133","author":"Lee","year":"2006","journal-title":"Development"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1100\/tsw.2007.71","article-title":"Evaluating the role of Wnt signal transduction in promoting the development of the heart","volume":"7","author":"Eisenberg","year":"2007","journal-title":"Sci. World J."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.devcel.2006.12.011","article-title":"Notch signaling is essential for ventricular chamber development","volume":"12","author":"Melgar","year":"2007","journal-title":"Dev. Cell"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4080","DOI":"10.1242\/dev.125724","article-title":"Cardiac contraction activates endocardial Notch signaling to modulate chamber maturation in zebrafish","volume":"142","author":"Samsa","year":"2015","journal-title":"Development"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.ydbio.2019.01.001","article-title":"The zinc finger protein Zfpm1 modulates ventricular trabeculation through Neuregulin-ErbB signalling","volume":"446","author":"Yang","year":"2019","journal-title":"Dev. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41390-020-0760-6","article-title":"Dysregulation of Notch signaling in cardiac mesenchymal cells of patients with tetralogy of Fallot","volume":"88","author":"Kozyrev","year":"2020","journal-title":"Pediatr. Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3611","DOI":"10.1242\/dev.025361","article-title":"Frs2alpha-deficiency in cardiac progenitors disrupts a subset of FGF signals required for outflow tract morphogenesis","volume":"135","author":"Zhang","year":"2008","journal-title":"Development"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1038\/s41598-019-39078-5","article-title":"Nkx2-5 Second Heart Field Target Gene Ccdc117 Regulates DNA Metabolism and Proliferation","volume":"9","author":"Horton","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/PL00008193","article-title":"Loss of function of the Prx1 and Prx2 homeobox genes alters architecture of the great elastic arteries and ductus arteriosus","volume":"436","author":"Bergwerff","year":"2000","journal-title":"Virchows Arch."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Zhao, C.M., Peng, L.Y., Li, L., Liu, X.Y., Wang, J., Zhang, X.L., Yuan, F., Li, R.G., Qiu, X.B., and Yang, Y.Q. (2015). PITX2 Loss-of-Function Mutation Contributes to Congenital Endocardial Cushion Defect and Axenfeld-Rieger Syndrome. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0124409"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2470","DOI":"10.1101\/gad.907301","article-title":"The murine winged helix transcription factors, Foxc1 and Foxc2, are both required for cardiovascular development and somitogenesis","volume":"15","author":"Kume","year":"2001","journal-title":"Genes. Dev."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/35065105","article-title":"Tbx1 haploinsufficieny in the DiGeorge syndrome region causes aortic arch defects in mice","volume":"410","author":"Lindsay","year":"2001","journal-title":"Nature"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.cardiores.2004.01.030","article-title":"The transcriptional repressor Tbx3 delineates the developing central conduction system of the heart","volume":"62","author":"Hoogaars","year":"2004","journal-title":"Cardiovasc. Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"dev167361","DOI":"10.1242\/dev.167361","article-title":"Embryonic Tbx3(+) cardiomyocytes form the mature cardiac conduction system by progressive fate restriction","volume":"145","author":"Mohan","year":"2018","journal-title":"Development"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"18617","DOI":"10.1073\/pnas.1919379117","article-title":"T-box transcription factor 3 governs a transcriptional program for the function of the mouse atrioventricular conduction system","volume":"117","author":"Mohan","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1002\/cbin.11738","article-title":"Tbx18 promoted the conversion of human-induced pluripotent stem cell-derived cardiomyocytes into sinoatrial node-like pacemaker cells","volume":"46","author":"Zhang","year":"2022","journal-title":"Cell Biol. Int."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"9181","DOI":"10.1073\/pnas.1405411111","article-title":"Pitx2-microRNA pathway that delimits sinoatrial node development and inhibits predisposition to atrial fibrillation","volume":"111","author":"Wang","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"4107","DOI":"10.1242\/dev.01265","article-title":"The T-Box transcription factor Tbx5 is required for the patterning and maturation of the murine cardiac conduction system","volume":"131","author":"Moskowitz","year":"2004","journal-title":"Development"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1002\/dvdy.20580","article-title":"Differentiation of cardiac Purkinje fibers requires precise spatiotemporal regulation of Nkx2-5 expression","volume":"235","author":"Harris","year":"2006","journal-title":"Dev. Dyn."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.ydbio.2006.12.044","article-title":"Nkx2.5 cell-autonomous gene function is required for the postnatal formation of the peripheral ventricular conduction system","volume":"303","author":"Meysen","year":"2007","journal-title":"Dev. Biol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1128\/MCB.00860-14","article-title":"MyoR modulates cardiac conduction by repressing Gata4","volume":"35","author":"Harris","year":"2015","journal-title":"Mol. Cell Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1172\/JCI44470","article-title":"Notch signaling regulates murine atrioventricular conduction and the formation of accessory pathways","volume":"121","author":"Rentschler","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1186\/s13287-020-01794-5","article-title":"Enrichment differentiation of human induced pluripotent stem cells into sinoatrial node-like cells by combined modulation of BMP, FGF, and RA signaling pathways","volume":"11","author":"Liu","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1002\/bdra.20796","article-title":"Hand factors as regulators of cardiac morphogenesis and implications for congenital heart defects","volume":"91","author":"Vincentz","year":"2011","journal-title":"Birth Defects Res. A Clin. Mol. Teratol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"3395","DOI":"10.1242\/dev.097360","article-title":"Bmp signaling represses Vegfa to promote outflow tract cushion development","volume":"140","author":"Bai","year":"2013","journal-title":"Development"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/S0140-6736(18)31940-8","article-title":"Prenatal exome sequencing analysis in fetal structural anomalies detected by ultrasonography (PAGE): A cohort study","volume":"393","author":"Lord","year":"2019","journal-title":"Lancet"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/S0092-8674(04)00405-2","article-title":"Nkx2-5 pathways and congenital heart disease; loss of ventricular myocyte lineage specification leads to progressive cardiomyopathy and complete heart block","volume":"117","author":"Pashmforoush","year":"2004","journal-title":"Cell"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/gm54","article-title":"Molecular genetics of atrial fibrillation","volume":"1","author":"Damani","year":"2009","journal-title":"Genome Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/nature06007","article-title":"Variants conferring risk of atrial fibrillation on chromosome 4q25","volume":"448","author":"Gudbjartsson","year":"2007","journal-title":"Nature"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1161\/CIRCRESAHA.107.161182","article-title":"Pitx2c and Nkx2-5 are required for the formation and identity of the pulmonary myocardium","volume":"101","author":"Mommersteeg","year":"2007","journal-title":"Circ. Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s13073-018-0582-x","article-title":"Clinical exome sequencing for fetuses with ultrasound abnormalities and a suspected Mendelian disorder","volume":"10","author":"Normand","year":"2018","journal-title":"Genome Med."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Yi, T., Sun, H., Fu, Y., Hao, X., Sun, L., Zhang, Y., Han, J., Gu, X., Liu, X., and Guo, Y. (2022). Genetic and Clinical Features of Heterotaxy in a Prenatal Cohort. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.818241"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Li, M., Ye, B., Chen, Y., Gao, L., Wu, Y., and Cheng, W. (2023). Analysis of genetic testing in fetuses with congenital heart disease of single atria and\/or single ventricle in a Chinese prenatal cohort. BMC Pediatr., 23.","DOI":"10.1186\/s12887-023-04382-7"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13023-021-02167-8","article-title":"Estimating the frequency of causal genetic variants in foetuses with congenital heart defects: A Chinese cohort study","volume":"17","author":"Lu","year":"2022","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1002\/uog.19042","article-title":"Clinical application of targeted next-generation sequencing in fetuses with congenital heart defect","volume":"52","author":"Hu","year":"2018","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Tan, M., Wang, X., Liu, H., Peng, X., Yang, Y., Yu, H., Xu, L., Li, J., and Cao, H. (2022). Genetic Diagnostic Yield and Novel Causal Genes of Congenital Heart Disease. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.941364"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1002\/uog.23532","article-title":"Comprehensive evaluation of genetic variants using chromosomal microarray analysis and exome sequencing in fetuses with congenital heart defect","volume":"58","author":"Qiao","year":"2021","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1002\/uog.21883","article-title":"Contribution of single-gene defects to congenital cardiac left-sided lesions in the prenatal setting","volume":"56","author":"Sun","year":"2020","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1002\/uog.18915","article-title":"Whole exome sequencing as a diagnostic adjunct to clinical testing in fetuses with structural abnormalities","volume":"51","author":"Fu","year":"2018","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1111\/1471-0528.16546","article-title":"A report on the impact of rapid prenatal exome sequencing on the clinical management of 52 ongoing pregnancies: A retrospective review","volume":"128","author":"Dempsey","year":"2021","journal-title":"Bjog"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Kuci\u0144ska-Chahwan, A., Geremek, M., Roszkowski, T., Bijok, J., Massalska, D., Ciebiera, M., Correia, H., Pereira-Caetano, I., Barreta, A., and Obersztyn, E. (2022). Implementation of Exome Sequencing in Prenatal Diagnosis and Impact on Genetic Counseling: The Polish Experience. Genes, 13.","DOI":"10.3390\/genes13050724"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1111\/cge.13536","article-title":"Lessons from exome sequencing in prenatally diagnosed heart defects: A basis for prenatal testing","volume":"95","author":"Westphal","year":"2019","journal-title":"Clin. Genet."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/cge.13774","article-title":"Prenatal exome sequencing in fetuses with congenital heart defects","volume":"98","author":"Li","year":"2020","journal-title":"Clin. Genet."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"e39","DOI":"10.1111\/1471-0528.16616","article-title":"Evidence to Support the Clinical Utility of Prenatal Exome Sequencing in Evaluation of the Fetus with Congenital Anomalies: Scientific Impact Paper No. 64 [February] 2021","volume":"128","author":"Mone","year":"2021","journal-title":"Bjog"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1002\/ehf2.14209","article-title":"Genetic aetiology distribution of 398 foetuses with congenital heart disease in the prenatal setting","volume":"10","author":"Yi","year":"2023","journal-title":"ESC Heart Fail."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13039-023-00664-y","article-title":"Contribution of genetic variants to congenital heart defects in both singleton and twin fetuses: A Chinese cohort study","volume":"17","author":"Lin","year":"2024","journal-title":"Mol. Cytogenet."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1038\/s41436-020-0791-8","article-title":"The prevalence of genetic diagnoses in fetuses with severe congenital heart defects","volume":"22","author":"Lugthart","year":"2020","journal-title":"Genet. Med."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1002\/pd.6168","article-title":"Prenatal diagnosis for fetuses with isolated and non-isolated congenital heart defects using chromosomal microarray and exome sequencing","volume":"42","author":"Xing","year":"2022","journal-title":"Prenat. Diagn."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1038\/gim.2017.31","article-title":"Whole-exome sequencing on deceased fetuses with ultrasound anomalies: Expanding our knowledge of genetic disease during fetal development","volume":"19","author":"Yates","year":"2017","journal-title":"Genet. Med."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1111\/aogs.14053","article-title":"The potential diagnostic yield of whole exome sequencing in pregnancies complicated by fetal ultrasound anomalies","volume":"100","author":"Diderich","year":"2021","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Lai, T.H.T., Au, L.K.S., Lau, Y.T.E., Lo, H.M., Chan, K.Y.K., Cheung, K.W., Ma, T.W.L., Leung, W.C., Kong, C.W., and Shu, W. (2022). Application of Prenatal Whole Exome Sequencing for Structural Congenital Anomalies-Experience from a Local Prenatal Diagnostic Laboratory. Healthcare, 10.","DOI":"10.3390\/healthcare10122521"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Leung, G.K.C., Mak, C.C.Y., Fung, J.L.F., Wong, W.H.S., Tsang, M.H.Y., Yu, M.H.C., Pei, S.L.C., Yeung, K.S., Mok, G.T.K., and Lee, C.P. (2018). Identifying the genetic causes for prenatally diagnosed structural congenital anomalies (SCAs) by whole-exome sequencing (WES). BMC Med. Genom., 11.","DOI":"10.1186\/s12920-018-0409-z"},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Sun, H., Hao, X., Wang, X., Zhou, X., Zhang, Y., Liu, X., Han, J., Gu, X., Sun, L., and Zhao, Y. (2020). Genetics and Clinical Features of Noncompaction Cardiomyopathy in the Fetal Population. Front. Cardiovasc. Med., 7.","DOI":"10.3389\/fcvm.2020.617561"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1002\/pd.6534","article-title":"The evolving genetic etiology of conotruncal anomalies","volume":"44","author":"Sacco","year":"2024","journal-title":"Prenat. Diagn."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/s41436-019-0731-7","article-title":"The use of fetal exome sequencing in prenatal diagnosis: A points to consider document of the American College of Medical Genetics and Genomics (ACMG)","volume":"22","author":"Monaghan","year":"2020","journal-title":"Genet. Med."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1002\/uog.24842","article-title":"Evolving fetal phenotypes and clinical impact of progressive prenatal exome sequencing pathways: Cohort study","volume":"59","author":"Mone","year":"2022","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.ajog.2022.08.040","article-title":"Prenatal exome and genome sequencing for fetal structural abnormalities","volume":"228","author":"Vora","year":"2023","journal-title":"Am. J. Obstet. Gynecol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/4\/1720\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T05:21:24Z","timestamp":1770873684000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/4\/1720"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,10]]},"references-count":136,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["ijms27041720"],"URL":"https:\/\/doi.org\/10.3390\/ijms27041720","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,10]]}}}