{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T15:16:42Z","timestamp":1784906202545,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,1,23]],"date-time":"2017-01-23T00:00:00Z","timestamp":1485129600000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development","award":["HHSN275201100001I"],"award-info":[{"award-number":["HHSN275201100001I"]}]},{"name":"Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development","award":["HHSN27500005"],"award-info":[{"award-number":["HHSN27500005"]}]},{"name":"Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development","award":["NICHD Contract N01-DK-73431"],"award-info":[{"award-number":["NICHD Contract N01-DK-73431"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2017,1,20]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Hypoplastic right heart syndrome (HRHS) is a rare congenital defect characterized by underdevelopment of the right heart structures commonly accompanied by an atrial septal defect. Familial HRHS reports suggest genetic factor involvement. We examined the role of copy number variants (CNVs) in HRHS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We genotyped 32 HRHS cases identified from all New York State live births (1998\u20132005) using Illumina HumanOmni2.5 microarrays. CNVs were called with PennCNV and prioritized if they were \u226520 Kb, contained \u226510 SNPs and had minimal overlap with CNVs from in\u2010house controls, the Database of Genomic Variants, HapMap3, and Childrens Hospital of Philadelphia database.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 28 CNVs in 17 cases; several encompassed genes important for right heart development. One case had a 2p16\u20102p23 duplication spanning <jats:italic>LBH<\/jats:italic>, a limb and heart development transcription factor. <jats:italic>Lbh<\/jats:italic> mis\u2010expression results in right ventricular hypoplasia and pulmonary valve defects. This duplication also encompassed <jats:italic>SOS1<\/jats:italic>, a factor associated with pulmonary valve stenosis in Noonan syndrome. <jats:italic>Sos1<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice display thin and poorly trabeculated ventricles. In another case, we identified a 1.5 Mb deletion associated with Williams\u2010Beuren syndrome, a disorder that includes valvular malformations. A third case had a 24 Kb deletion upstream of the TGF\u03b2 ligand <jats:italic>ITGB8<\/jats:italic>. Embryos genetically null for <jats:italic>Itgb8<\/jats:italic>, and its intracellular interactant <jats:italic>Band 4.1B<\/jats:italic>, display lethal cardiac phenotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>To our knowledge, this is the first study of CNVs in HRHS. We identified several rare CNVs that overlap genes related to right ventricular wall and valve development, suggesting that genetics plays a role in HRHS and providing clues for further investigation. Birth Defects Research 109:16\u201326, 2017. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.23586","type":"journal-article","created":{"date-parts":[[2016,12,25]],"date-time":"2016-12-25T02:42:46Z","timestamp":1482633766000},"page":"8-15","source":"Crossref","is-referenced-by-count":13,"title":["Rare copy number variants in a population\u2010based investigation of hypoplastic right heart syndrome"],"prefix":"10.1002","volume":"109","author":[{"given":"Aggeliki","family":"Dimopoulos","sequence":"first","affiliation":[{"name":"Division of Intramural Population Health Research <i>Eunice Kennedy Shriver<\/i> National Institute of Child Health and Human Development, National Institutes of Health Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Sicko","sequence":"additional","affiliation":[{"name":"Division of Genetics Wadsworth Center, New York State Department of Health Albany New 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