{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T20:58:54Z","timestamp":1788382734539,"version":"build-2803163510"},"reference-count":57,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,10,11]],"date-time":"2013-10-11T00:00:00Z","timestamp":1381449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Congenital heart defects (CHDs) are common malformations, affecting four to eight per 1,000 total births. Conotruncal defects are an important pathogenetic subset of CHDs, comprising nearly 20% of the total. Although both environmental and genetic factors are known to contribute to the occurrence of conotruncal defects, the causes remain unknown for most. To identify novel candidate genes\/loci, we used array comparative genomic hybridization to detect chromosomal microdeletions\/duplications. From a population base of 974,579 total births born during 1999\u20132004, we screened 389 California infants born with tetralogy of Fallot or d\u2010transposition of the great arteries. We found that 1.7% (5\/288) of males with a conotruncal defect had sex chromosome aneuploidy, a sevenfold increased frequency (relative risk\u2009=\u20097.0; 95% confidence interval 2.9\u201316.9). We identified eight chromosomal microdeletions\/duplications for conotruncal defects. From these duplications and deletions, we found five high priority candidate genes (<jats:italic>GATA4<\/jats:italic>, <jats:italic>CRKL<\/jats:italic>, <jats:italic>BMPR1A<\/jats:italic>, <jats:italic>SNAI2<\/jats:italic>, and <jats:italic>ZFHX4<\/jats:italic>). This is the initial report that sex chromosome aneuploidy is associated with conotruncal defects among boys. These chromosomal microduplications\/deletions provide evidence that <jats:italic>GATA4<\/jats:italic>, <jats:italic>SNAI2<\/jats:italic>, and <jats:italic>CRKL<\/jats:italic> are highly dosage sensitive genes involved in outflow tract development. Genome wide screening for copy number variation can be productive for identifying novel genes\/loci contributing to non\u2010syndromic common malformations. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36291","type":"journal-article","created":{"date-parts":[[2013,10,14]],"date-time":"2013-10-14T11:52:27Z","timestamp":1381751547000},"page":"397-406","source":"Crossref","is-referenced-by-count":21,"title":["Identification of novel candidate gene loci and increased sex chromosome aneuploidy among infants with conotruncal heart defects"],"prefix":"10.1002","volume":"164","author":[{"given":"Kazutoyo","family":"Osoegawa","sequence":"first","affiliation":[{"name":"Center for Genetics Children's Hospital Oakland Research Institute Children's Hospital Research Center Oakland Oakland California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Iovannisci","sequence":"additional","affiliation":[{"name":"Center for Genetics Children's Hospital Oakland Research Institute Children's Hospital Research Center Oakland Oakland California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Lin","sequence":"additional","affiliation":[{"name":"Center for Genetics Children's Hospital Oakland Research Institute Children's Hospital Research Center Oakland Oakland California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Parodi","sequence":"additional","affiliation":[{"name":"Center for Genetics Children's Hospital Oakland Research Institute Children's Hospital Research Center Oakland Oakland California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Schultz","sequence":"additional","affiliation":[{"name":"Center for Genetics Children's Hospital Oakland Research Institute Children's Hospital Research Center Oakland Oakland California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary M.","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Stanford University School of Medicine Stanford California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward J.","family":"Lammer","sequence":"additional","affiliation":[{"name":"Center for Genetics Children's Hospital Oakland Research Institute Children's Hospital Research Center Oakland Oakland California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,10,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1203"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2010.01373.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1086\/513607"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201932"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1755-8166-3-3"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/gm137"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35217"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2011.10.003"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp427"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0146-0005(96)80062-0"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a113979"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01827"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.415"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.29.1830"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1086\/378157"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.183216"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0012-1606(98)80005-5"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20438"},{"key":"e_1_2_6_20_1","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1542\/peds.56.3.462","article-title":"Congenital heart disease in 49, XXXXY syndrome","volume":"56","author":"Karsh RB","year":"1975","journal-title":"Pediatrics"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10024-002-0004-2"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh700"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19971017)72:2<180::AID-AJMG10>3.0.CO;2-J"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20541"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1070"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/35065105"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.8.10.8132"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00247-1"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1995.tb04064.x"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2005.12.003"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201956"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9410"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9926(199606)53:6<374::AID-TERA8>3.0.CO;2-#"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.a.10027"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.052191"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19990319)83:3<201::AID-AJMG11>3.0.CO;2-V"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1159\/000091924"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.030619"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.070391"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2008.05.059"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.25.3231"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20345"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.4.489"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.5986507"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20648"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.08.003"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.21.4274"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2011.02235.x"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.22846"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.052183"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI38194"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2010.211"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2009.182642"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1407"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32896"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01174"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14632-6"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20565"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.36291","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.36291","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T09:20:19Z","timestamp":1696584019000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.36291"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,10,11]]},"references-count":57,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2014,2]]}},"alternative-id":["10.1002\/ajmg.a.36291"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.36291","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,10,11]]}}}