{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T18:54:29Z","timestamp":1758394469774,"version":"3.40.5"},"reference-count":37,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,5,29]],"date-time":"2021-05-29T00:00:00Z","timestamp":1622246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ovotesticular differences of sexual development (OT\u2010DSD) are rare genetic variances defined by the coexistence of both testicular and ovarian tissues. Various molecular etiologies including <jats:italic>SRY<\/jats:italic> translocation or <jats:italic>SOX9<\/jats:italic> pathogenic variants with different modes of inheritance have been associated with 46,XX OT\u2010DSD. Here we describe a child diagnosed with <jats:italic>SRY<\/jats:italic>\u2010negative 46,XX OT\u2010DSD after completing a series of complex clinical genetic analyses, including chromosomal microarray, DSD gene panel (sequencing and deletion\/duplication analysis), whole exome sequencing, and whole genome sequencing. Of these, only whole genome sequencing reported a pathogenic duplication in a non\u2010coding region that contains the RevSex regulatory element, which modifies <jats:italic>SOX9<\/jats:italic> expression and is associated with 46,XX OT\u2010DSD and complete sex reversal. This is the first clinical RevSex duplication detected by clinical whole genome sequencing. We highlight the utility of whole genome sequencing in shortening the diagnostic odyssey and the importance of optimal counseling through a team\u2010based multi\u2010specialty approach for patients with DSDs.<\/jats:p>","DOI":"10.1002\/ajmg.a.62373","type":"journal-article","created":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T09:21:59Z","timestamp":1622798519000},"page":"2782-2788","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Whole genome sequencing identifies a cryptic <scp><i>SOX9<\/i><\/scp> regulatory element duplication underlying a case of 46,<scp>XX<\/scp> ovotesticular difference of sexual development"],"prefix":"10.1002","volume":"185","author":[{"given":"Zhiyu","family":"Qian","sequence":"first","affiliation":[{"name":"Department of Pediatrics David Geffen School of Medicine at UCLA  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9411-2913","authenticated-orcid":false,"given":"Katheryn","family":"Grand","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Freedman","sequence":"additional","affiliation":[{"name":"Department of Surgery Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria C.","family":"Nieto","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences California State University  Hayward California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Behlmann","sequence":"additional","affiliation":[{"name":"PerkinElmer Genomics  Duluth Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bahareh M.","family":"Schweiger","sequence":"additional","affiliation":[{"name":"Department of Pediatrics David Geffen School of Medicine at UCLA  Los Angeles California USA"},{"name":"Department of Pediatrics Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1181-7828","authenticated-orcid":false,"given":"Pedro A.","family":"Sanchez\u2010Lara","sequence":"additional","affiliation":[{"name":"Department of Pediatrics David Geffen School of Medicine at UCLA  Los Angeles California USA"},{"name":"Department of Pediatrics Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,5,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2011-100255"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2013.09.005"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2006-0005"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1010311"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2008.10.101"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07784-9"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000481896"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07784-9"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpurol.2016.04.001"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdrc.21145"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aas9408"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006520"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-19-0067"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37101"},{"key":"e_1_2_8_16_1","first-page":"4","article-title":"Disorders of sex development: Diagnostic approaches and management options\u2014An islamic perspective","volume":"18","author":"Jurayyan A.","year":"2011","journal-title":"The Malaysian Journal of Medical Sciences"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2017.07.004"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2014-102864"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02000779"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2006-0738"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1159\/000442975"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20205017"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.21037\/tau-19-726"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.2350\/14-04-1466-PB.1"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12976"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2012.235"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-662-56282-6_64"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0686-8"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62202"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2016.04.002"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.5603\/FHC.a2015.0021"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2021.105875"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1177\/0891243213503203"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-8002-1_21"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-0500-5-476"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2013.10.001"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2013.10.001"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.620162"}],"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.62373","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62373","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62373","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T02:55:57Z","timestamp":1693277757000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62373"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,29]]},"references-count":37,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2021,9]]}},"alternative-id":["10.1002\/ajmg.a.62373"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62373","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"type":"print","value":"1552-4825"},{"type":"electronic","value":"1552-4833"}],"subject":[],"published":{"date-parts":[[2021,5,29]]},"assertion":[{"value":"2020-12-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}