{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T05:28:25Z","timestamp":1781760505604,"version":"3.54.5"},"reference-count":11,"publisher":"The Endocrine Society","issue":"11","license":[{"start":{"date-parts":[[2019,8,28]],"date-time":"2019-08-28T00:00:00Z","timestamp":1566950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"publisher","award":["2011\/20747-8"],"award-info":[{"award-number":["2011\/20747-8"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"publisher","award":["2014\/06570-6"],"award-info":[{"award-number":["2014\/06570-6"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Gonadal sex determination is a complex genetic process by which an embryonic primordium is driven to form an ovary or a testis, which requires a delicate dosage balance involving many genes. Disruption in this molecular pathway can lead to differences of sex development (DSD). Although some genetic mechanisms leading to 46,XY DSD have been elucidated, little is known about copy-number variation (CNV) causing testicular or ovotesticular 46,XX DSD. We describe a 20-year natural history of a man with SRY-negative 46,XX who was born with atypical male external genitalia, aortic coarctation, and bilateral blepharophimosis-ptosis. The molecular study identified a de novo heterozygous 3-Mb 15q26.2 deletion, a gene-poor locus containing NR2F2, which encodes the nuclear receptor COUP-TFII that is highly expressed in ovary and cardiac arteries. Immunohistochemistry confirmed the low COUP-TFII expression on his ovotestis tissue. Monosomy of 15q26.2, encompassing the NR2F2 gene, may act as a Z-factor regulating the male sex determination negatively. This finding supports a novel type of CNV resulting in DSD in an individual who developed male puberty spontaneously.<\/jats:p>","DOI":"10.1210\/js.2019-00241","type":"journal-article","created":{"date-parts":[[2019,8,28]],"date-time":"2019-08-28T10:05:53Z","timestamp":1566986753000},"page":"2107-2113","source":"Crossref","is-referenced-by-count":31,"title":["The Natural History of a Man With Ovotesticular 46,XX DSD Caused by a Novel 3-Mb 15q26.2 Deletion Containing NR2F2 Gene"],"prefix":"10.1210","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6602-8319","authenticated-orcid":false,"given":"Gianna","family":"Carvalheira","sequence":"first","affiliation":[{"name":"Department of Morphology and Genetics, Division of Genetics, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea M","family":"Malinverni","sequence":"additional","affiliation":[{"name":"Department of Morphology and Genetics, Division of Genetics, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo, Brazil"},{"name":"Department of Pathology, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Moys\u00e9s-Oliveira","sequence":"additional","affiliation":[{"name":"Department of Morphology and Genetics, Division of Genetics, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Ueta","sequence":"additional","affiliation":[{"name":"Department of Morphology and Genetics, Division of Genetics, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Cardili","sequence":"additional","affiliation":[{"name":"Department of Pathology, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia","family":"Monteagudo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreia L G","family":"Mathez","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ieda T","family":"Verreschi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A","family":"Maluf","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiovascular, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rcia E F","family":"Shida","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Pediatric Surgery, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mila T C","family":"Leite","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Pediatric Surgery, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Mazzotti","sequence":"additional","affiliation":[{"name":"Center for Sleep and Circadian Neurobiology, University of Pensylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Isabel","family":"Melaragno","sequence":"additional","affiliation":[{"name":"Department of Morphology and Genetics, Division of Genetics, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8516-966X","authenticated-orcid":false,"given":"Magnus R","family":"Dias-da-Silva","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo, Brazil"},{"name":"Department of Medicine, Division of Endocrinology, Laboratory of Molecular and Translational Endocrinology, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2019,8,28]]},"reference":[{"issue":"8","key":"2019103013343076300_bib1","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1093\/humrep\/dex210","article-title":"Incidence, prevalence, diagnostic delay, morbidity, mortality and socioeconomic status in males with 46,XX disorders of sex development: a nationwide study","volume":"32","author":"Berglund","year":"2017","journal-title":"Hum Reprod"},{"issue":"1","key":"2019103013343076300_bib2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000445088","article-title":"Disorders of sex development with testicular differentiation in SRY-negative 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