{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:46:59Z","timestamp":1787021219949,"version":"build-2736575974"},"reference-count":35,"publisher":"The Endocrine Society","issue":"10","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Duplications occurring upstream of the SOX9 gene have been identified in a limited subset of patients with 46,XX testicular\/ovotesticular differences\/disorders of sex development (DSD). However, comprehensive understanding regarding their clinical presentation and diagnosis is limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To gain further insight into the diagnosis of a large cohort of 46,XX individuals with duplications upstream of SOX9.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed data of 46,XX\/SRY-negative individuals with SOX9 upstream duplications. Clinical data were recorded, and genetic etiologies were investigated using karyotyping, fluorescence in situ hybridization (FISH) for SRY analysis, microarray analysis, multiplex ligation-dependent probe amplification (MLPA) and next-generation sequencing panels including whole genome sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We analyzed 12 individuals with 46,XX karyotype who had heterozygous duplications upstream of SOX9, ranging from 107 to 941\u2005kb. Ages at diagnosis ranged from 0.1 to 55 years. Seven (58%) had testicular\/ovotesticular DSD, while 5 (41%) were asymptomatic carriers detected through family screening. There was no significant correlation between duplication size and genital\/gonadal phenotype. The duplication was inherited from the father (n = 3) or an asymptomatic mother (n = 2). In one family, a duplication missed by the 300K microarray was detected by MLPA and confirmed with 750K microarray.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>46,XX individuals with SOX9 upstream duplications may exhibit no symptoms, but thorough family screening is crucial due to the potential inheritance and testicular\/ovotesticular DSD risk in subsequent generations. We emphasize the effectiveness of high-resolution microarray analysis (&amp;gt;500K) as the primary diagnostic tool for 46,XX\/SRY-negative testicular\/ovotesticular DSD individuals, enabling thorough genome-wide assessment of copy number variations and detecting small alterations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgaf020","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T23:18:25Z","timestamp":1736551105000},"page":"e3482-e3488","source":"Crossref","is-referenced-by-count":4,"title":["Phenotypes Linked to Duplication Upstream of\n                    <i>SOX9<\/i>\n                    : New Insights Into Presentation and Diagnosis"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9809-0977","authenticated-orcid":false,"given":"Edip","family":"Unal","sequence":"first","affiliation":[{"name":"Department of Pediatric Endocrinology, Dicle University, School of Medicine , 21280, Diyarbakir ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8730-3968","authenticated-orcid":false,"given":"Aysel","family":"Tekmenuray-Unal","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Antalya Education and Research Hospital , 07100, Antalya ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9776-555X","authenticated-orcid":false,"given":"Atilla","family":"Cayir","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Erzurum Region Education and Research Hospital , 25070, Erzurum ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4664-7435","authenticated-orcid":false,"given":"Esra Deniz","family":"Papatya Cakir","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Bak\u0131rk\u00f6y Dr. Sadi Konuk Education and Research Hospital , 34147, Istanbul ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurcan","family":"Beyazit","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Dicle University, School of Medicine , 21280, Diyarbakir ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baris","family":"Kolbasi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Dicle University, School of Medicine , 21280, Diyarbakir ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7588-9807","authenticated-orcid":false,"given":"Busra","family":"Gurpinar Tosun","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Marmara University School of Medicine , 34854, Istanbul ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gokhan","family":"Yigit","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Medical Center G\u00f6ttingen , 37073, G\u00f6ttingen ,","place":["Germany"]},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Lower Saxony , 37075, G\u00f6ttingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne","family":"Zibat","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Medical Center G\u00f6ttingen , 37073, G\u00f6ttingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Wollnik","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Medical Center G\u00f6ttingen , 37073, G\u00f6ttingen ,","place":["Germany"]},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Lower Saxony , 37075, G\u00f6ttingen ,","place":["Germany"]},{"name":"Cluster of Excellence \u201cMultiscale Bioimaging: From Molecular Machines to Networks of Excitable Cells\u201d (MBExC), University of G\u00f6ttingen , 37075, G\u00f6ttingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6374-5884","authenticated-orcid":false,"given":"Huseyin","family":"Demirbilek","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Hacettepe University School of Medicine , 06100, Ankara ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2658-6866","authenticated-orcid":false,"given":"Tulay","family":"Guran","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Marmara University School of Medicine , 34854, Istanbul 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