{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T16:48:02Z","timestamp":1765039682569,"version":"build-2065373602"},"reference-count":47,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T00:00:00Z","timestamp":1681948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["NO. 2016YFC1000104","81971619"],"award-info":[{"award-number":["NO. 2016YFC1000104","81971619"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NO. 2016YFC1000104","81971619"],"award-info":[{"award-number":["NO. 2016YFC1000104","81971619"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>(1) Background: The objective of this study was to investigate the diagnostic value of chromosomal microarray analysis (CMA) for congenital heart defects (CHDs) with different cardiac phenotypes and extracardiac abnormalities (ECAs) and to explore the pathogenic genetic factors of CHDs. (2) Methods: We collected fetuses diagnosed with CHDs by echocardiography at our hospital from January 2012 to December 2021. We analyzed the CMA results of 427 fetuses with CHDs. We then categorized the CHD into different groups according to two dimensions: different cardiac phenotypes and whether it was combined with ECAs. The correlation between the numerical chromosomal abnormalities (NCAs) and copy number variations (CNVs) with CHDs was analyzed. Statistical analyses, including Chi-square tests and t-tests, were performed on the data using IBM SPSS and GraphPad Prism. (3) Results: In general, CHDs with ECAs increased the detection rate for CA, especially the conotruncal defects. CHD combined with the thoracic and abdominal walls and skeletal, thymic and multiple ECAs, were more likely to exhibit CA. Among the CHD phenotypes, VSD and AVSD were associated with NCA, while DORV may be associated with NCA. The cardiac phenotypes associated with pCNVs were IAA (type A and B), RAA, TAPVC, CoA and TOF. In addition, IAA, B, RAA, PS, CoA and TOF were also associated with 22q11.2DS. The length distribution of the CNV was not significantly different between each CHD phenotype. We detected twelve CNV syndromes, of which six syndromes may be related to CHDs. The pregnancy outcome in this study suggests that termination of pregnancy with fetal VSD and vascular abnormality is more dependent on genetic diagnosis, whereas the outcome in other phenotypes of CHDs may be associated with other additional factors. (4) Conclusions: CMA examination for CHDs is still necessary. We should identify the existence of fetal ECAs and specific cardiac phenotypes, which are helpful for genetic counseling and prenatal diagnosis.<\/jats:p>","DOI":"10.3390\/diagnostics13081493","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T01:33:43Z","timestamp":1682040823000},"page":"1493","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Diagnostic Value of Chromosomal Microarray Analysis for Fetal Congenital Heart Defects with Different Cardiac Phenotypes and Extracardiac Abnormalities"],"prefix":"10.3390","volume":"13","author":[{"given":"Simin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Ultrasound, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China"},{"name":"Beijing Maternal and Child Health Care Hospital, Beijing 100026, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China"},{"name":"Beijing Maternal and Child Health Care Hospital, Beijing 100026, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Pei","sequence":"additional","affiliation":[{"name":"Beijing Maternal and Child Health Care Hospital, Beijing 100026, China"},{"name":"Department of Obstetric, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jijing","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China"},{"name":"Beijing Maternal and Child Health Care Hospital, Beijing 100026, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaowei","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China"},{"name":"Beijing Maternal and Child Health Care Hospital, Beijing 100026, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yani","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Obstetric, Peking University People\u2019s Hospital, Beijing 100032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China"},{"name":"Beijing Maternal and Child Health Care Hospital, Beijing 100026, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Beijing Maternal and Child Health Care Hospital, Beijing 100026, China"},{"name":"Prenatal Diagnosis Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangfei","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, Beijing Friendship Hospital, Capital Medical University, Beijing 100032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinyu","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100026, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6836-9192","authenticated-orcid":false,"given":"Qingqing","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China"},{"name":"Beijing Maternal and Child Health Care Hospital, Beijing 100026, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.ajhg.2008.12.014","article-title":"Population Analysis of Large Copy Number Variants and Hotspots of Human Genetic Disease","volume":"84","author":"Itsara","year":"2009","journal-title":"Am. J. Hum. Genet."},{"unstructured":"Christianson, A., Howson, C.P., and Modell, B. (2005). March of Dimes: Global Report on Birth Defects, the Hidden Toll of Dying and Disabled Children, White Plains.","key":"ref_2"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/nrcardio.2010.166","article-title":"The changing epidemiology of congenital heart disease","volume":"8","author":"Zomer","year":"2011","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1002\/bdra.20403","article-title":"Seeking causes: Classifying and evaluating congenital heart defects in etiologic studies","volume":"79","author":"Botto","year":"2007","journal-title":"Birth Defects Res. Part A Clin. Mol. Teratol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e25999","DOI":"10.1097\/MD.0000000000025999","article-title":"Diagnostic accuracy and value of chromosomal microarray analysis for chromosomal abnormalities in prenatal detection: A prospective clinical study","volume":"100","author":"Huang","year":"2021","journal-title":"Medicine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ejogrb.2017.03.007","article-title":"The clinical use of chromosomal microarray analysis in detection of fetal chromosomal rearrangements: A study from China Mainland","volume":"212","author":"Wu","year":"2017","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1056\/NEJMoa1203382","article-title":"Chromosomal Microarray versus Karyotyping for Prenatal Diagnosis","volume":"367","author":"Wapner","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.1080\/14767058.2019.1670793","article-title":"Prenatal diagnosis of submicroscopic chromosomal aberrations in fetuses with congenital cystic adenomatoid malformation by chromosomal microarray analysis","volume":"34","author":"Deng","year":"2021","journal-title":"J. Matern.-Fetal Neonatal Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2312","DOI":"10.1016\/j.jacc.2021.09.1358","article-title":"Abnormal Extracardiac Development in Fetuses with Congenital Heart Disease","volume":"78","author":"Dovjak","year":"2021","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1002\/uog.6309","article-title":"Extracardiac lesions and chromosomal abnormalities associated with major fetal heart defects: Comparison of intrauterine, postnatal and postmortem diagnoses","volume":"33","author":"Song","year":"2009","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.acvd.2016.01.006","article-title":"Associated genetic syndromes and extracardiac malformations strongly influence outcomes of fetuses with congenital heart diseases","volume":"109","author":"Bensemlali","year":"2016","journal-title":"Arch. Cardiovasc. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"244.e1","DOI":"10.1016\/j.ajog.2017.10.225","article-title":"Prenatal chromosomal microarray analysis in fetuses with congenital heart disease: A prospective cohort study","volume":"218","author":"Wang","year":"2018","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_13","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_14","doi-asserted-by":"crossref","first-page":"120","DOI":"10.3389\/fped.2016.00120","article-title":"What Is New in Genetics of Congenital Heart Defects?","volume":"4","author":"Digilio","year":"2016","journal-title":"Front. Pediatr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"F520","DOI":"10.1136\/adc.2004.070342","article-title":"Fetal echocardiography in trisomy 18","volume":"90","author":"Moyano","year":"2005","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.ijcard.2006.12.020","article-title":"Left superior vena cava in pediatric cardiology associated with extra-cardiac anomalies","volume":"123","author":"Postema","year":"2008","journal-title":"Int. J. Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"818241","DOI":"10.3389\/fgene.2022.818241","article-title":"Genetic and Clinical Features of Heterotaxy in a Prenatal Cohort","volume":"13","author":"Yi","year":"2022","journal-title":"Front. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1002\/pd.3943","article-title":"Detection rates of clinically significant genomic alterations by microarray analysis for specific anomalies detected by ultrasound","volume":"32","author":"Shaffer","year":"2012","journal-title":"Prenat. Diagn."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1002\/pd.4383","article-title":"Prenatal diagnosis of congenital heart defect by genome-wide high-resolution SNP array","volume":"34","author":"Liao","year":"2014","journal-title":"Prenat. Diagn."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1002\/uog.13236","article-title":"Detection of submicroscopic chromosomal aberrations by array-based comparative genomic hybridization in fetuses with congenital heart disease","volume":"43","author":"Yan","year":"2014","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.neubiorev.2019.10.020","article-title":"Impact of copy number variation on human neurocognitive deficits and congenital heart defects: A systematic review","volume":"108","author":"Savory","year":"2020","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00439-004-1204-9","article-title":"Non-recurrent 17p11.2 deletions are generated by homologous and non-homologous mechanisms","volume":"116","author":"Shaw","year":"2005","journal-title":"Hum. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/S0168-9525(02)02592-1","article-title":"Genome architecture, rearrangements and genomic disorders","volume":"18","author":"Stankiewicz","year":"2002","journal-title":"Trends Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/nrg.2015.25","article-title":"Mechanisms underlying structural variant formation in genomic disorders","volume":"17","author":"Carvalho","year":"2016","journal-title":"Nat. Rev. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e7","DOI":"10.1136\/archdischild-2018-316634","article-title":"Correction: Genetic characterisation of 22q11.2 variations and prevalence in patients with congenital heart disease","volume":"105","author":"Hou","year":"2020","journal-title":"Arch. Dis. Child."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.3892\/mmr.2014.2564","article-title":"Detection of chromosomal abnormalities and the 22q11 microdeletion in fetuses with congenital heart defects","volume":"10","author":"Lv","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e22660","DOI":"10.1002\/jcla.22660","article-title":"Copy number variations in the GATA4, NKX2-5, TBX5, BMP4 CRELD1, and 22q11.2 gene regions in Chinese children with sporadic congenital heart disease","volume":"33","author":"Li","year":"2019","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.ajhg.2007.09.014","article-title":"22q11.2 Distal Deletion: A Recurrent Genomic Disorder Distinct from DiGeorge Syndrome and Velocardiofacial Syndrome","volume":"82","author":"Ou","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.ajhg.2015.03.007","article-title":"Copy-Number Variation of the Glucose Transporter Gene SLC2A3 and Congenital Heart Defects in the 22q11.2 Deletion Syndrome","volume":"96","author":"Mlynarski","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1002\/uog.15998","article-title":"Fetal cardiac axis in tetralogy of Fallot: Associations with prenatal findings, genetic anomalies and postnatal outcome","volume":"50","author":"Zhao","year":"2017","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1002\/ajmg.c.31762","article-title":"Other genomic disorders and congenital heart disease","volume":"184","author":"Lalani","year":"2020","journal-title":"Am. J. Med. Genet. Part C Semin. Med. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1086\/444549","article-title":"Duplication of the MECP2 Region Is a Frequent Cause of Severe Mental Retardation and Progressive Neurological Symptoms in Males","volume":"77","author":"Bauters","year":"2005","journal-title":"Am. J. Hum. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/ng1933","article-title":"Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders","volume":"39","author":"Durand","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1002\/ajmg.1320460110","article-title":"Human smooth muscle myosin heavy chain gene mapped to chromosomal region 16q12","volume":"46","author":"Matsuoka","year":"1993","journal-title":"Am. J. Med. Genet."},{"key":"ref_35","first-page":"371","article-title":"Smooth-muscle contraction without smooth-muscle myosin","volume":"2","author":"Morano","year":"2000","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S1074-7613(00)00017-0","article-title":"Fli-1 Is Required for Murine Vascular and Megakaryocytic Development and Is Hemizygously Deleted in Patients with Thrombocytopenia","volume":"13","author":"Hart","year":"2000","journal-title":"Immunity"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1038\/ng1363","article-title":"NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome","volume":"36","author":"Tonkin","year":"2004","journal-title":"Nat. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/gim.2015.60","article-title":"Exome sequencing identifies rare variants in multiple genes in atrioventricular septal defect","volume":"18","author":"Manickaraj","year":"2016","journal-title":"Genet. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.ajhg.2019.07.002","article-title":"Haploinsufficiency of the Notch Ligand DLL1 Causes Variable Neurodevelopmental Disorders","volume":"105","author":"Segebrecht","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1002\/ajmg.a.32992","article-title":"Genomic duplication of PTPN11 is an uncommon cause of Noonan syndrome","volume":"149a","author":"Graham","year":"2009","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1016\/j.cell.2007.04.036","article-title":"A Molecular Pathway Including Id2, Tbx5, and Nkx2-5 Required for Cardiac Conduction System Development","volume":"129","author":"Moskowitz","year":"2007","journal-title":"Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/90123","article-title":"Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation","volume":"28","author":"Hiroi","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/nature01827","article-title":"GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5","volume":"424","author":"Garg","year":"2003","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/S0735-1097(19)31174-X","article-title":"Neurocognitive deficits in adult congenital heart disease: Does coronary artery disease add insult to injury?","volume":"73","author":"Morello","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1161\/CIRCRESAHA.116.309048","article-title":"Neurodevelopmental Abnormalities and Congenital Heart Disease: Insights Into Altered Brain Maturation","volume":"120","author":"Morton","year":"2017","journal-title":"Circ. Res."},{"key":"ref_46","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_47","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.ppedcard.2010.06.011","article-title":"Effects of congenital heart disease on brain development","volume":"29","author":"McQuillen","year":"2010","journal-title":"Prog. Pediatr. Cardiol."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/8\/1493\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:20:08Z","timestamp":1760124008000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/8\/1493"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,20]]},"references-count":47,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["diagnostics13081493"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics13081493","relation":{},"ISSN":["2075-4418"],"issn-type":[{"type":"electronic","value":"2075-4418"}],"subject":[],"published":{"date-parts":[[2023,4,20]]}}}