{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:11:05Z","timestamp":1790161865405,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2013,8,5]],"date-time":"2013-08-05T00:00:00Z","timestamp":1375660800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>The <jats:italic>NR5A1<\/jats:italic> gene encodes for steroidogenic factor 1, a nuclear receptor that regulates proper adrenal and gonadal development and function. Mutations identified by <jats:italic>NR5A1<\/jats:italic> sequencing have been associated with disorders of sex development (DSD), ranging from sex reversal to severe hypospadias in 46,XY patients and premature ovarian failure (POF) in 46,XX patients. Previous reports have identified four families with a history of both 46,XY DSD and 46,XX POF carrying segregating <jats:italic>NR5A1<\/jats:italic> sequence mutations. Recently, three 46,XY DSD sporadic cases with <jats:italic>NR5A1<\/jats:italic> microdeletions have been reported. Here, we identify the first <jats:italic>NR5A1<\/jats:italic> microdeletion transmitted in a pedigree with both 46,XY DSD and 46,XX POF. A 46,XY individual with DSD due to gonadal dysgenesis was born to a young mother who developed POF. Array CGH analysis revealed a maternally inherited 0.23\u2009Mb microdeletion of chromosome 9q33.3, including the <jats:italic>NR5A1<\/jats:italic> gene. Based on this finding, we screened patients with unexplained 46,XY DSD (n\u2009=\u200911), proximal hypospadias (n\u2009=\u200921) and 46,XX POF (n\u2009=\u200936) for possible <jats:italic>NR5A1<\/jats:italic> copy\u2010number variations (CNVs) via multiplex ligation\u2010dependent probe amplification (MLPA), but did not identify any additional CNVs involving <jats:italic>NR5A1<\/jats:italic>. These data suggest that <jats:italic>NR5A1<\/jats:italic> CNVs are an infrequent cause of these disorders but that array CGH and MLPA are useful genomic screening tools to uncover the genetic basis of such unexplained cases. This case is the first report of a familial <jats:italic>NR5A1<\/jats:italic> CNV transmitting in a pedigree, causing both the male and female phenotypes associated with <jats:italic>NR5A1<\/jats:italic> mutations, and the first report of a <jats:italic>NR5A1<\/jats:italic> CNV associated with POF. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36084","type":"journal-article","created":{"date-parts":[[2013,8,5]],"date-time":"2013-08-05T21:08:03Z","timestamp":1375736883000},"page":"2487-2494","source":"Crossref","is-referenced-by-count":27,"title":["Screening and familial characterization of copy\u2010number variations in <i>NR5A1<\/i> in 46,XY disorders of sex development and premature ovarian failure"],"prefix":"10.1002","volume":"161","author":[{"given":"Steven M.","family":"Harrison","sequence":"first","affiliation":[{"name":"Department of Urology University of Texas Southwestern Medical Center Dallas Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian M.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melise","family":"Keays","sequence":"additional","affiliation":[{"name":"Department of Urology University of Texas Southwestern Medical Center Dallas Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Candace F.","family":"Granberg","sequence":"additional","affiliation":[{"name":"Department of Urology University of Texas Southwestern Medical Center Dallas Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Villanueva","sequence":"additional","affiliation":[{"name":"Department of Urology University of Texas Southwestern Medical Center Dallas 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A.","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawel","family":"Stankiewicz","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda A.","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Urology University of Texas Southwestern Medical Center Dallas Texas"},{"name":"Children's Medical Center at Dallas Dallas Texas"},{"name":"McDermott Center for Human Growth and Development University of Texas Southwestern Medical Center Dallas 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