{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T13:16:37Z","timestamp":1789996597861,"version":"4.0.1"},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,3,12]],"date-time":"2013-03-12T00:00:00Z","timestamp":1363046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic><jats:styled-content style=\"fixed-case\">NR<\/jats:styled-content>5<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>1<\/jats:italic> loss\u2010of\u2010function mutations are increasingly found to be the cause of 46,<jats:styled-content style=\"fixed-case\">XY<\/jats:styled-content> disorders of sex development (<jats:styled-content style=\"fixed-case\">DSD<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine the presence of <jats:italic><jats:styled-content style=\"fixed-case\">NR<\/jats:styled-content>5A1<\/jats:italic> mutations in an <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>ustralasian cohort of 17 46,<jats:styled-content style=\"fixed-case\">XY DSD<\/jats:styled-content> patients with presumed androgen insensitivity syndrome (<jats:styled-content style=\"fixed-case\">AIS<\/jats:styled-content>) who were negative for androgen receptor gene (<jats:italic><jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content><\/jats:italic>) mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Exons 2\u20107 of <jats:italic><jats:styled-content style=\"fixed-case\">NR<\/jats:styled-content>5A1<\/jats:italic> were <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> amplified and sequenced. Gene expression and cellular localization studies were performed on a novel <jats:italic><jats:styled-content style=\"fixed-case\">NR<\/jats:styled-content>5A1<\/jats:italic> variant c.74<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>&gt;<jats:styled-content style=\"fixed-case\">G<\/jats:styled-content> (p.<jats:styled-content style=\"fixed-case\">Y<\/jats:styled-content>25<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>) identified in this study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified one novel mutation, c.74<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>&gt;<jats:styled-content style=\"fixed-case\">G<\/jats:styled-content> (p.<jats:styled-content style=\"fixed-case\">Y<\/jats:styled-content>25<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>) in a patient characterized by penoscrotal hypospadias with bifid scrotum. He had elevated testosterone and gonadotropins in early infancy. Functional analysis of p.<jats:styled-content style=\"fixed-case\">Y<\/jats:styled-content>25<jats:styled-content style=\"fixed-case\">C <\/jats:styled-content><jats:italic>in vitro<\/jats:italic> demonstrated reduced transcriptional activation by <jats:styled-content style=\"fixed-case\">SF<\/jats:styled-content>\u20101 and partially impaired nuclear localization in a proportion of transfected human adrenal <jats:styled-content style=\"fixed-case\">NCI<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>295<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content> cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This is the first reported case of a <jats:styled-content style=\"fixed-case\">DSD<\/jats:styled-content> patient with a <jats:italic><jats:styled-content style=\"fixed-case\">NR<\/jats:styled-content>5<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>1<\/jats:italic> mutation and elevated testosterone levels. Our finding supports evaluation of <jats:italic><jats:styled-content style=\"fixed-case\">NR<\/jats:styled-content>5<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>1<\/jats:italic> mutations in 46,<jats:styled-content style=\"fixed-case\">XY DSD<\/jats:styled-content> patients with a range of testosterone levels.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.12012","type":"journal-article","created":{"date-parts":[[2012,8,22]],"date-time":"2012-08-22T03:05:59Z","timestamp":1345604759000},"page":"545-550","source":"Crossref","is-referenced-by-count":30,"title":["A novel <i><scp>NR<\/scp>5<scp>A<\/scp>1<\/i> variant in an infant with elevated testosterone from an <scp>A<\/scp>ustralasian cohort of 46,<scp>XY<\/scp> patients with disorders of sex development"],"prefix":"10.1111","volume":"78","author":[{"given":"Joyce Y.","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Clinical Chemistry Mater Hospital South Brisbane QLD Australia"},{"name":"University of Queensland Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan N.","family":"McGown","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry Mater Hospital South Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Lin","sequence":"additional","affiliation":[{"name":"Developmental Endocrinology Research Group Clinical and Molecular Genetics Unit University College London Institute of Child Health, University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Achermann","sequence":"additional","affiliation":[{"name":"Developmental Endocrinology Research Group Clinical and Molecular Genetics Unit University College London Institute of Child Health, University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Paediatric Endocrinology Mater Children's Hospital South Brisbane QLD Australia"},{"name":"Mater Medical Research Institute South Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Cowley","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry Mater Hospital South Brisbane QLD Australia"},{"name":"University of Queensland Brisbane QLD Australia"},{"name":"Mater Medical Research Institute South Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salim","family":"Aftimos","sequence":"additional","affiliation":[{"name":"Northern Regional Genetics Service Auckland Hospital Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen A.","family":"Neville","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Sydney Children's Hospital Randwick NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine S.","family":"Choong","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes Princess Margaret Hospital for Children, School of Paediatrics and Child Health University of Western Australia Subiaco WA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Cotterill","sequence":"additional","affiliation":[{"name":"Department of Paediatric Endocrinology Mater Children's Hospital South Brisbane QLD Australia"},{"name":"University of Queensland Brisbane QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,3,12]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2007.06.003"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-0024"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1515\/JPEM.2007.20.8.893"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.85.2.658"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2006.11.003"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000152036"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2003.10.096"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/9629"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.87.4.8376"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0935"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-1672"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-09-0067"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.09.009"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-07-0113"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-3169"},{"key":"e_1_2_6_17_1","volume-title":"Endocrinology Expected Values and SI Unit Conversion Tables","author":"Esoterix","year":"2011"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2010.11.006"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-11-0944"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2004.04705.x"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2009.02.009"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2007.06.001"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.15.9.1505"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-11-0392"},{"key":"e_1_2_6_25_1","first-page":"73","article-title":"Update \u2013 Steroidogenic factor 1 (SF\u20101, NR5A1)","volume":"35","author":"K\u00f6hler B.","year":"2010","journal-title":"Minerva Endocrinologica"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0806228"},{"key":"e_1_2_6_27_1","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1515\/jpem-2008-210609","article-title":"Molecular analysis of the AR and SRD5A2 genes in patients with 46,XY disorders of sex development","volume":"21","author":"Choi J.","year":"2008","journal-title":"Journal of Pediatric Endocrinology and Metabolism"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.84.12.4713"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0188-4409(99)00074-0"}],"container-title":["Clinical Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcen.12012","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cen.12012","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cen.12012","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cen.12012","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T11:08:21Z","timestamp":1700651301000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cen.12012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,3,12]]},"references-count":28,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013,4]]}},"alternative-id":["10.1111\/cen.12012"],"URL":"https:\/\/doi.org\/10.1111\/cen.12012","archive":["Portico"],"relation":{},"ISSN":["0300-0664","1365-2265"],"issn-type":[{"value":"0300-0664","type":"print"},{"value":"1365-2265","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,3,12]]}}}