{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:30:27Z","timestamp":1791203427311,"version":"4.2.0"},"reference-count":27,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2015,4,1]],"date-time":"2015-04-01T00:00:00Z","timestamp":1427846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH\/NICHD","award":["R01 HD064667"],"award-info":[{"award-number":["R01 HD064667"]}]},{"name":"NIH\/NIGMS Initiative for Maximizing Student Development (IMSD)","award":["R25 GM056929-16"],"award-info":[{"award-number":["R25 GM056929-16"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:sec><jats:label\/><jats:p>HEY2 is a basic helix\u2010loop\u2010helix (bHLH) transcription factor that plays an important role in the developing mammalian heart and brain. In humans, nonsynonymous mutations in <jats:italic>HEY2<\/jats:italic> have been described in patients with atrial ventricular septal defects, and a subset of individuals with chromosomal deletions involving <jats:italic>HEY2<\/jats:italic> have cardiac defects and cognitive impairment. Less is known about the potential effects of HEY2 overexpression. Here, we describe a female child with tetralogy of Fallot who developed severe right ventricular outflow tract obstruction due to a combination of infundibular and valvular pulmonary stenosis. She was also noted to have hypotonia, lower extremity weakness, fine motor delay and speech delay. A copy number variation (CNV) detection analysis followed by real\u2010time quantitative PCR analysis revealed a single gene duplication of <jats:italic>HEY2<\/jats:italic>. This is the only duplication involving <jats:italic>HEY2<\/jats:italic> identified in our database of over 70,000 individuals referred for CNV analysis. In the developing heart, overexpression of HEY2 is predicted to cause decreased expression of the cardiac transcription factor GATA4 which, in turn, has been shown to cause tetralogy of Fallot. In mice, misexpression of <jats:italic>Hey2<\/jats:italic> in the developing brain leads to inhibition of neurogenesis and promotion of gliogenesis. Hence, duplication of <jats:italic>HEY2<\/jats:italic> may be a contributing factor to both the congenital heart defects and the neurodevelopmental problems evident in our patient. These results suggest that individuals with <jats:italic>HEY2<\/jats:italic> duplications should be screened for congenital heart defects and monitored closely for evidence of developmental delay and\/or cognitive impairment. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37086","type":"journal-article","created":{"date-parts":[[2015,4,2]],"date-time":"2015-04-02T21:54:35Z","timestamp":1428011675000},"page":"2145-2149","source":"Crossref","is-referenced-by-count":15,"title":["Duplication of <i>HEY2<\/i> in cardiac and neurologic development"],"prefix":"10.1002","volume":"167","author":[{"given":"Valerie K.","family":"Jordan","sequence":"first","affiliation":[{"name":"Department of Molecular Physiology and Biophysics Baylor College of Medicine Houston TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill A.","family":"Rosenfeld","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seema R.","family":"Lalani","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daryl A.","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics Baylor College of Medicine Houston TX"},{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston TX"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,4]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.9.6381"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35780"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(02)01149-1"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-004-2389-x"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.20.8960-8970.2005"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(02)01150-8"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34255"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.12.014"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.0880"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(99)00080-5"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2000.9884"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2009-10-11-r125"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.238"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1999.9454"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9410"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9390"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300448200"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.252648999"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2005.09.006"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2012.95"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl475"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.083501.108"},{"key":"e_1_2_6_24_1","doi-asserted-by":"crossref","unstructured":"ThorssonT RussellWW El\u2010KashlanN SoemediR LevineJ GeislerSB AckleyT Tomita\u2010MitchellA RosenfeldJA TopfA TayehM GoodshipJ InnisJW KeavneyB RussellMW.2014. 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