{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T21:50:41Z","timestamp":1781214641177,"version":"3.54.1"},"reference-count":51,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2011,2,2]],"date-time":"2011-02-02T00:00:00Z","timestamp":1296604800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2011,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>The left ventricular outflow tract (LVOT) defects aortic valve stenosis (AVS), coarctation of the aorta (COA), and hypoplastic left heart syndrome (HLHS) represent an embryologically related group of congenital cardiovascular malformations. They are common and cause substantial morbidity and mortality. Prior evidence suggests a strong genetic component in their causation.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We selected <jats:italic>NRG1<\/jats:italic>, <jats:italic>ERBB3<\/jats:italic>, and <jats:italic>ERBB4<\/jats:italic> of the epidermal growth factor receptor (EGFR) signaling pathway as candidate genes for investigation of association with LVOT defects based on the importance of this pathway in cardiac development and the phenotypes in knockout mouse models. Single nucleotide polymorphism (SNP) genotyping was performed on 343 affected case\u2010parent trios of European ancestry.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>We identified a specific haplotype in intron 3 of <jats:italic>ERBB4<\/jats:italic> that was positively associated with the combined LVOT defects phenotype (<jats:italic>p<\/jats:italic> = 0.0005) and in each anatomic defect AVS, COA, and HLHS separately. Mutation screening of individuals with an LVOT defect failed to identify a coding sequence or splice site change in <jats:italic>ERBB4<\/jats:italic>. RT\u2010PCR on lymphoblastoid cells from LVOT subjects did not show altered splice variant ratios among those homozygous for the associated haplotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>These results suggest <jats:italic>ERBB4<\/jats:italic> is associated with LVOT defects. Further replication will be required in separate cohorts to confirm the consistency of the observed association. Birth Defects Research (Part A), 2011. \u00a9 2011 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.20764","type":"journal-article","created":{"date-parts":[[2011,2,2]],"date-time":"2011-02-02T18:28:32Z","timestamp":1296671312000},"page":"162-168","source":"Crossref","is-referenced-by-count":46,"title":["Association of common variants in <i>ERBB4<\/i> with congenital left ventricular outflow tract obstruction defects"],"prefix":"10.1002","volume":"91","author":[{"given":"Kim L.","family":"McBride","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria A.","family":"Zender","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara M.","family":"Fitzgerald\u2013Butt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikki 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