{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T18:15:07Z","timestamp":1789755307056,"version":"4.0.1"},"reference-count":19,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,6,10]],"date-time":"2011-06-10T00:00:00Z","timestamp":1307664000000},"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":[[2011,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Context\u2002<\/jats:bold> Aromatase deficiency in women is a rare 46, XX disorder of sex differentiation characterized by a defect in catalysing oestrogens from androgens.<\/jats:p><jats:p><jats:bold>Objective\u2002<\/jats:bold> To better understand this rare disorder, we searched for mutations in the <jats:italic>CYP19A1<\/jats:italic> gene of an affected girl and analysed their functional consequences.<\/jats:p><jats:p><jats:bold>Design and patient\u2002<\/jats:bold> We examined a girl presenting with clitoral hypertrophy at birth and mild maternal virilization (acne) during pregnancy.<\/jats:p><jats:p><jats:bold>Main outcome measurement\u2002<\/jats:bold> A genotype\u2013phenotype correlation was found.<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold> By direct sequencing of the <jats:italic>CYP19A1<\/jats:italic> gene, we identified a heterozygous A&gt;G mutation (c. A1374G) mutation in exon IX, leading to the missense p.N411S in the P450Aro protein and a heterozygous placenta promoter variant \u221241 base pairs upstream of exon I.1. Aromatase enzyme activity was completely lost when the mutant p.N411S protein was expressed in COS\u20101 cells. The placenta promoter variant had a significantly reduced (\u221250%) transactivation ability compared to wild\u2010type.<\/jats:p><jats:p><jats:bold>Conclusion\u2002<\/jats:bold> Our data describe a novel loss\u2010of\u2010function missense mutation in <jats:italic>CYP19A1<\/jats:italic> combined with the first\u2010described variant of the placenta promoter with a significant reduction in function, likely to be the molecular basis of this rare 46, XX disorder of sex development. This seems to represent a unique case of aromatase deficiency occurring <jats:italic>in utero<\/jats:italic> only.<\/jats:p>","DOI":"10.1111\/j.1365-2265.2011.04012.x","type":"journal-article","created":{"date-parts":[[2011,2,9]],"date-time":"2011-02-09T15:33:22Z","timestamp":1297265602000},"page":"39-43","source":"Crossref","is-referenced-by-count":26,"title":["Aromatase deficiency owing to a functional variant in the placenta promoter and a novel missense mutation in the <i>CYP19A1<\/i> gene"],"prefix":"10.1111","volume":"75","author":[{"given":"Annik","family":"Hauri\u2010Hohl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Meyer\u2010B\u00f6ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariarosaria","family":"Lang\u2010Muritano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Hauri\u2010Hohl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugen J.","family":"Schoenle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Biason\u2010Lauber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,6,10]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1210\/jcem.81.3.8772541","article-title":"Clinical review 78: aromatase deficiency in women and men: would you have predicted the phenotypes?","volume":"81","author":"Bulun S.E.","year":"1996","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2004-823023"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-0760(03)00359-5"},{"key":"e_1_2_8_5_2","first-page":"126","article-title":"Aromatase research and its clinical significance","volume":"61","author":"Czajka\u2010Oraniec I.","year":"2010","journal-title":"Endokrynologia Polska"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1159\/000249159"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-1743"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-1181"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.82.6.1739"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.23.10619"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.485"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.12.11.1764"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.80.12.3689"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1515\/JPEM.1998.11.5.657"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-030433"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199707103370204"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.5560040605"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-3224"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-1218"},{"key":"e_1_2_8_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.24.11673"}],"container-title":["Clinical Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2265.2011.04012.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2265.2011.04012.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,15]],"date-time":"2023-10-15T23:10:46Z","timestamp":1697411446000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2265.2011.04012.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,6,10]]},"references-count":19,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2011,7]]}},"alternative-id":["10.1111\/j.1365-2265.2011.04012.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2265.2011.04012.x","archive":["Portico"],"relation":{},"ISSN":["0300-0664","1365-2265"],"issn-type":[{"value":"0300-0664","type":"print"},{"value":"1365-2265","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,6,10]]}}}