{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T13:16:53Z","timestamp":1774617413814,"version":"3.50.1"},"reference-count":75,"publisher":"The Endocrine Society","issue":"3","license":[{"start":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["320030-197725"],"award-info":[{"award-number":["320030-197725"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003086","name":"Education Department of Basque Government","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003086","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Steroidogenic factor 1 (NR5A1\/SF-1) is a nuclear receptor that regulates sex development, steroidogenesis, and reproduction. Genetic variants in NR5A1\/SF-1 are common among differences of sex development (DSD) and associate with a wide range of phenotypes, but their pathogenic mechanisms remain unclear.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Novel, likely disease-causing NR5A1\/SF-1 variants from the SF1next cohort of individuals with DSD were characterized to elucidate their pathogenic effect.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Different in silico tools were used to predict the impact of novel NR5A1\/SF-1 variants on protein function. An extensive literature review was conducted to compare and select the best functional studies for testing the pathogenic effect of the variants in a classic cell culture model. The missense NR5A1\/SF-1 variants were tested on the promoter luciferase reporter vector -152CYP11A1_pGL3 in HEK293T cells and assessed for their cytoplasmic\/nuclear localization by Western blot.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Thirty-five novel NR5A1\/SF-1 variants were identified in the SF1next cohort. Seventeen missense NR5A1\/SF-1 variants were functionally tested. Transactivation assays showed reduced activity for 40% of the variants located in the DNA binding domain and variable activity for variants located elsewhere. Translocation assessment revealed 3 variants (3\/17) with affected nuclear translocation. No clear genotype-phenotype, structure-function correlation was found.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Genetic analyses and functional assays do not explain the observed wide phenotype of individuals with these novel NR5A1\/SF-1 variants. In 9 individuals, additional likely disease-causing variants in other genes were found, strengthening the hypothesis that the broad phenotype of DSD associated with NR5A1\/SF-1 variants may be caused by an oligogenic mechanism.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgae251","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T19:01:57Z","timestamp":1713294117000},"page":"e675-e693","source":"Crossref","is-referenced-by-count":10,"title":["Characterization of 35 Novel <i>NR5A1<\/i>\/SF-1 Variants Identified in Individuals With Atypical Sexual Development: The SF1next Study"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2669-4170","authenticated-orcid":false,"given":"Rawda","family":"Naamneh Elzenaty","sequence":"first","affiliation":[{"name":"Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern , 3010 Bern ,","place":["Switzerland"]},{"name":"Department of BioMedical Research, University of Bern , 3008 Bern ,","place":["Switzerland"]},{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern , 3012 Bern ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Idoia","family":"Martinez de Lapiscina","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern , 3010 Bern ,","place":["Switzerland"]},{"name":"Department of BioMedical Research, University of Bern , 3008 Bern ,","place":["Switzerland"]},{"name":"Research into the Genetics and Control of Diabetes and other Endocrine Disorders, Biobizkaia Health Research Institute, Cruces University Hospital , 48903 Barakaldo ,","place":["Spain"]},{"name":"CIBER de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Instituto de Salud Carlos III , 28029 Madrid ,","place":["Spain"]},{"name":"CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III , 28029 Madrid ,","place":["Spain"]},{"name":"Department of Rare Endocrine Conditions, Endo-ERN , 1105 Amsterdam ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chrysanthi","family":"Kouri","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern , 3010 Bern ,","place":["Switzerland"]},{"name":"Department of BioMedical Research, University of Bern , 3008 Bern ,","place":["Switzerland"]},{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern , 3012 Bern ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kay-Sara","family":"Sauter","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern , 3010 Bern ,","place":["Switzerland"]},{"name":"Department of BioMedical Research, University of Bern , 3008 Bern ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grit","family":"Sommer","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern , 3010 Bern ,","place":["Switzerland"]},{"name":"Department of BioMedical Research, University of Bern , 3008 Bern ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Casta\u00f1o","sequence":"additional","affiliation":[{"name":"Research into the Genetics and Control of Diabetes and other Endocrine Disorders, Biobizkaia Health Research Institute, Cruces University Hospital , 48903 Barakaldo ,","place":["Spain"]},{"name":"CIBER de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Instituto de Salud Carlos III , 28029 Madrid ,","place":["Spain"]},{"name":"CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III , 28029 Madrid ,","place":["Spain"]},{"name":"Department of Rare Endocrine Conditions, Endo-ERN , 1105 Amsterdam ,","place":["The Netherlands"]},{"name":"Department of Pediatric Endocrinology, Cruces University Hospital , 48903 Barakaldo ,","place":["Spain"]},{"name":"Department of Pediatrics, University of the Basque Country (UPV-EHU) , 48903 Leioa ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4568-5504","authenticated-orcid":false,"given":"Christa E","family":"Fl\u00fcck","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern , 3010 Bern ,","place":["Switzerland"]},{"name":"Department of BioMedical 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Zenodo. 2024. 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