{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:34:11Z","timestamp":1783488851796,"version":"3.55.0"},"reference-count":27,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[2016,8,24]],"date-time":"2016-08-24T00:00:00Z","timestamp":1471996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2016,8,24]],"date-time":"2016-08-24T00:00:00Z","timestamp":1471996800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Res Paediatr"],"published-print":{"date-parts":[[2017]]},"abstract":"<b><i>Background:<\/i><\/b> Undervirilized 46,XY males with bifid scrotum often pose a diagnostic challenge, and the majority of cases typically do not receive a genetic diagnosis. <i>NR5A1<\/i> mutations can be seen in 10-20% of the cases and are a relatively common cause of undervirilization. <b><i>Methods:<\/i><\/b> Whole-exome sequencing was utilized to study 10 undervirilized 46,XY subjects with bifid scrotum. <b><i>Results:<\/i><\/b> Exome sequencing identified novel <i>NR5A1<\/i> variants, both affecting exon 7, in 2 of the 10 subjects with bifid scrotum. Subject 1 had a heterozygous frameshift variant, c.1150delC, p.Leu384fsTer1, within the ligand-binding domain inherited from his unaffected father. Subject 2 had a novel splice-site variant c.1139-2T>C, affecting the canonical splice acceptor site for exon 7 and also disrupting the ligand-binding domain. Both subjects had serum testosterone levels within the normal range as infants. <b><i>Conclusions:<\/i><\/b> We describe two novel <i>NR5A1<\/i> variants, demonstrating mutations in this gene as a common cause of milder cases of 46,XY undervirilization. Whole-exome sequencing results yielded the diagnosis in 2 out of 10 cases without a previous diagnosis, supporting the value of this approach. Significant genotype-phenotype variability was also noted with Subject 1's paternal inheritance from his unaffected father.<\/jats:p>","DOI":"10.1159\/000448754","type":"journal-article","created":{"date-parts":[[2016,8,23]],"date-time":"2016-08-23T21:01:21Z","timestamp":1471986081000},"page":"264-270","source":"Crossref","is-referenced-by-count":6,"title":["Two Unrelated Undervirilized 46,XY Males with Inherited NR5A1 Variants Identified by Whole-Exome Sequencing"],"prefix":"10.1159","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1017-9318","authenticated-orcid":false,"given":"Jonathan M.","family":"Swartz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Ciarlo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aser","family":"Abrha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Diamond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yee-Ming","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel N.","family":"Hirschhorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2016,8,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpurol.2006.03.004"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-2605"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2012.01879.x"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1093\/bmb\/ldt008"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2015.07.004"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-3169"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1038\/9629"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M002892200"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.87.4.8376"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-1672"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20588"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-09-0067"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1038\/ng.806"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi1110s43"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3063"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1677\/jme.0.0170139"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1159\/000431324"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1159\/000152036"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2010.11.035"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1159\/000320029"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-014-0209-2"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1159\/000338346"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1159\/000440862"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1111\/cen.12012"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2015.69"}],"container-title":["Hormone Research in Paediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/448754","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/448754","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T17:06:26Z","timestamp":1745427986000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000448754"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,24]]},"references-count":27,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2017,7,4]]}},"URL":"https:\/\/doi.org\/10.1159\/000448754","archive":["Portico"],"relation":{},"ISSN":["1663-2818","1663-2826"],"issn-type":[{"value":"1663-2818","type":"print"},{"value":"1663-2826","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,24]]}}}