{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T10:26:33Z","timestamp":1781778393341,"version":"3.54.5"},"reference-count":12,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T00:00:00Z","timestamp":1702252800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5K23DK119949\u201002"],"award-info":[{"award-number":["5K23DK119949\u201002"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5UM1HG006542\u201008"],"award-info":[{"award-number":["5UM1HG006542\u201008"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Bladder exstrophy epispadias complex (BEEC) encompasses a spectrum of conditions ranging from mild epispadias to the most severe form: omphalocele\u2014bladder exstrophy\u2014imperforate anus\u2014spinal defects (OEIS). BEEC involves abnormalities related to anatomical structures that are proposed to have a similar underlying etiology and pathogenesis. In general, BEEC, is considered to arise from a sequence of events in embryonic development and is believed to be a multi\u2010etiological disease with contributions from genetic and environmental factors. Several genes have been implicated and mouse models have been generated, including a knockout model of p63, which is involved in the synthesis of stratified epithelium. Mice lacking p63 have undifferentiated ventral urothelium. <jats:italic>MNX1<\/jats:italic> has also been implicated. In addition, cigarette smoking, diazepam and clomid have been implied as environmental factors due to their relative association. By in large, the etiology and pathogenesis of human BEEC is unknown. We performed de novo analysis of whole exome sequencing (WES) of germline samples from 31 unrelated trios where the probands have a diagnosis of BEEC syndrome. We also evaluated the DECIPHER database to identify copy number variants (CNVs) in genes in individuals with the search terms \u201cbladder exstrophy\u201d in an attempt to identify additional candidate genes within these regions. Several de novo variants were identified; however, a candidate gene is still unclear. This data further supports the multi\u2010etiological nature of BEEC.<\/jats:p>","DOI":"10.1002\/ajmg.a.63501","type":"journal-article","created":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T16:38:49Z","timestamp":1702399129000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["De novo variants identified by trio whole exome sequencing of bladder exstrophy epispadias complex"],"prefix":"10.1002","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1792-4029","authenticated-orcid":false,"given":"Angie C.","family":"Jelin","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics Johns Hopkins School of Medicine  Baltimore Maryland USA"},{"name":"McKusick\u2010Nathans Department of Genetic Medicine Johns Hopkins School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Wohler","sequence":"additional","affiliation":[{"name":"McKusick\u2010Nathans Department of Genetic Medicine Johns Hopkins School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renan","family":"Martin","sequence":"additional","affiliation":[{"name":"McKusick\u2010Nathans Department of Genetic Medicine Johns Hopkins School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Di Carlo","sequence":"additional","affiliation":[{"name":"Department of Pediatric Urology Johns Hopkins School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Isaacs","sequence":"additional","affiliation":[{"name":"Department of Pediatric Urology Johns Hopkins School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Pediatric Urology Johns Hopkins School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Michaud","sequence":"additional","affiliation":[{"name":"Department of Pediatric Urology Johns Hopkins School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Blakemore","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics Johns Hopkins School of Medicine  Baltimore Maryland USA"},{"name":"McKusick\u2010Nathans Department of Genetic Medicine Johns Hopkins School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6560-4281","authenticated-orcid":false,"given":"David","family":"Valle","sequence":"additional","affiliation":[{"name":"McKusick\u2010Nathans Department of Genetic Medicine Johns Hopkins School of Medicine  Baltimore Maryland USA"},{"name":"Department of Pediatrics Johns Hopkins School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5228-5613","authenticated-orcid":false,"given":"Nara","family":"Sobreira","sequence":"additional","affiliation":[{"name":"McKusick\u2010Nathans Department of Genetic Medicine Johns Hopkins School of Medicine  Baltimore Maryland USA"},{"name":"Department of Pediatrics Johns Hopkins School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Gearhart","sequence":"additional","affiliation":[{"name":"Department of Pediatric Urology Johns Hopkins School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2004.05170.x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpurol.2015.03.023"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.806"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.03.010"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(2001)9999:9999<00::AID-AJMG1094>3.0.CO;2-#"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23641"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"issue":"1","key":"e_1_2_10_9_1","first-page":"95","article-title":"Omphalocele\u2010exstrophy\u2010imperforate\u2010anus\u2010spina bifida (OEIS) complex in a male prenatally exposed to diazepam","volume":"26","author":"Lizcano\u2010Gil L. A.","year":"1995","journal-title":"Archives of Medical Research"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1016"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22769"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62103"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63501","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T05:39:31Z","timestamp":1719553171000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63501"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,11]]},"references-count":12,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1002\/ajmg.a.63501"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63501","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,11]]},"assertion":[{"value":"2023-07-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e63501"}}