{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:03:09Z","timestamp":1791388989632,"version":"4.3.3"},"reference-count":25,"publisher":"The Endocrine Society","issue":"10","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Differences of sex development (DSDs) are rare conditions with atypical chromosomal, gonadal, or anatomical sex. We describe 2 cases of 46,XY DSD due to complete gonadal dysgenesis, a 16-year-old female and a 45-year-old female, who both presented with primary amenorrhea and hirsutism. The 16-year-old had tall stature and normal-appearing female external genitalia but absent female secondary sex characteristics. Hormonal assessment revealed hypergonadotropic hypogonadism. The uterus appeared normal on transabdominal ultrasound. Testing revealed 46,XY karyotype and SRY+ using fluorescence in situ hybridization (FISH). 46,XY DSD genetic testing found a novel, heterozygous, likely pathogenic NR5A1 variant (NM_004959.5:c.1166_1180del). Low-dose transdermal estradiol was commenced for pubertal induction, planned for gradual uptitration before progestogen introduction. The 45-year-old female had osteoporosis and had been taking the oral contraceptive pill (OCP) long-term for previously misdiagnosed Turner syndrome. She had normal-appearing female external genitalia, tall stature, and no Turner syndrome features. Hormonal assessment was confounded by previous gonadectomy and OCP use. Testing revealed 46,XY karyotype and SRY+ using FISH. 46,XY DSD genetic testing revealed a novel, heterozygous, likely pathogenic variant of NR5A1 (NM_004959.5:c.489del). Hormone therapy was changed to transdermal estradiol\/progestogen. These cases highlight 2 novel NR5A1 variants associated with 46,XY DSD.<\/jats:p>","DOI":"10.1210\/jcemcr\/luaf187","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T08:33:33Z","timestamp":1755851613000},"source":"Crossref","is-referenced-by-count":2,"title":["Two Cases of 46,XY Differences of Sex Development Due to Gonadal Dysgenesis Associated With Novel <i>NR5A1<\/i> Variants"],"prefix":"10.1210","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5596-9095","authenticated-orcid":false,"given":"Joshua V","family":"Gialouris","sequence":"first","affiliation":[{"name":"Department of Andrology, Concord Hospital , Sydney, NSW 2139 ,","place":["Australia"]},{"name":"ANZAC Research Institute, University of Sydney , Sydney, NSW 2138 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0095-4459","authenticated-orcid":false,"given":"Pak Leng","family":"Cheong","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health, University of Sydney , Sydney, NSW 2052 ,","place":["Australia"]},{"name":"Department of Medical Genomics, Royal Prince Alfred Hospital , Sydney, NSW 2050 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stipe","family":"Zekanovic","sequence":"additional","affiliation":[{"name":"Department of Medical Genomics, Royal Prince Alfred Hospital , Sydney, NSW 2050 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1637-5117","authenticated-orcid":false,"given":"Mawson","family":"Wang","sequence":"additional","affiliation":[{"name":"ANZAC Research Institute, University of Sydney , Sydney, NSW 2138 ,","place":["Australia"]},{"name":"Department of Endocrinology and Metabolism, Concord Hospital , Sydney, NSW 2139 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