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Among congenital heart defects, conotruncal defects represent about 20% and are severe malformations with significant morbidity. <jats:italic>Insulin gene enhancer protein 1<\/jats:italic> (<jats:italic><jats:styled-content style=\"fixed-case\">ISL<\/jats:styled-content>1<\/jats:italic>) has been considered a candidate gene for conotruncal heart defects based on its embryonic expression pattern and heart defects induced in <jats:italic>Isl1<\/jats:italic> knockout mice. Nevertheless no mutation of <jats:italic><jats:styled-content style=\"fixed-case\">ISL<\/jats:styled-content>1<\/jats:italic> has been reported from any human subject with a heart defect. From a population base of 974,579 births during 1999\u20132004, we used multiplex ligation\u2010dependent probe amplification to screen for microdeletions\/duplications of <jats:italic><jats:styled-content style=\"fixed-case\">ISL<\/jats:styled-content>1<\/jats:italic> among 389 infants with tetralogy of Fallot or d\u2010transposition of the great arteries (d\u2010<jats:styled-content style=\"fixed-case\">TGA<\/jats:styled-content>). We also sequenced all exons of <jats:italic><jats:styled-content style=\"fixed-case\">ISL<\/jats:styled-content>1<\/jats:italic>. We identified a novel 20\u2010kb microdeletion encompassing the entire coding region of <jats:italic><jats:styled-content style=\"fixed-case\">ISL<\/jats:styled-content>1<\/jats:italic>, but not including either flanking gene, from an infant with d\u2010<jats:styled-content style=\"fixed-case\">TGA<\/jats:styled-content>. We confirmed that the deletion was caused by nonhomologous end joining mechanism. Sequencing of exons of <jats:italic><jats:styled-content style=\"fixed-case\">ISL<\/jats:styled-content>1<\/jats:italic> did not reveal any subject with a novel nonsynonymous mutation. This is the first report of an <jats:italic><jats:styled-content style=\"fixed-case\">ISL<\/jats:styled-content>1<\/jats:italic> mutation of a child with a congenital heart defect.<\/jats:p>","DOI":"10.1002\/mgg3.75","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T01:17:44Z","timestamp":1397783864000},"page":"341-351","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Haploinsufficiency of <i>insulin gene enhancer protein 1<\/i> (<i>ISL1<\/i>) is associated with d\u2010transposition of the great arteries"],"prefix":"10.1002","volume":"2","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 94609 California"},{"name":"Department of Pathology Stanford University School of Medicine Palo Alto 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 94609 California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Yun","sequence":"additional","affiliation":[{"name":"Center for Genetics Children's Hospital Oakland Research Institute Children's Hospital Research Center Oakland Oakland 94609 California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nebil","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Center for Genetics Children's Hospital Oakland Research Institute Children's Hospital Research Center Oakland Oakland 94609 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 94609 California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,4,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0085375"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm238"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6602121"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(03)00363-0"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046688"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a113979"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.03.010"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfs178"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030677"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)01886-7"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.183216"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.229202"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-11-1389"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.023671"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.86"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20541"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt958"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.89.6.887"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.10.029"},{"key":"e_1_2_7_22_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_7_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.052191"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36291"},{"key":"e_1_2_7_25_1","doi-asserted-by":"crossref","first-page":"891","DOI":"10.18388\/abp.2003_3622","article-title":"Non\u2010homologous DNA end joining","volume":"50","author":"Pastwa E.","year":"2003","journal-title":"Acta Biochim. 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