{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T01:37:21Z","timestamp":1790473041407,"version":"4.1.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T00:00:00Z","timestamp":1647820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The clinical profile and genetics of individuals with Disorders\/Differences of Sex Development (DSD) has not been reported in Ukraine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      We established the Ukrainian DSD Register and identified 682 DSD patients. This cohort includes, 357 patients (52.3% [303 patients with Turner syndrome)] with sex chromosome DSD, 119 (17.5%) with 46,XY DSD and 206 (30.2%) with 46,XX DSD. Patients with sex chromosome DSD and congenital adrenal hyperplasia (CAH, n=185) were excluded from further studies. Fluorescence\n                      <jats:italic>in situ<\/jats:italic>\n                      hybridization (FISH) was performed for eight 46,XX boys. 79 patients underwent Whole Exome Sequencing (WES).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The majority of patients with 46,XY and 46,XX DSD (n=140), were raised as female (56.3% and 61.9% respectively). WES (n=79) identified pathogenic (P) or likely pathogenic (LP) variants in 43% of the cohort. P\/LP variants were identified in the androgen receptor (\n                      <jats:italic>AR<\/jats:italic>\n                      ) and\n                      <jats:italic>NR5A1<\/jats:italic>\n                      genes (20.2%). Variants in other DSD genes including\n                      <jats:italic>AMHR2, HSD17B3, MYRF, ANOS1, FGFR11, WT1, DHX37, SRD5A1, GATA4, TBCE, CACNA1A<\/jats:italic>\n                      and\n                      <jats:italic>GLI2<\/jats:italic>\n                      were identified in 22.8% of cases. 83.3% of all P\/LP variants are novel. 35.3% of patients with a genetic diagnosis had an atypical clinical presentation. A known pathogenic variant in\n                      <jats:italic>WDR11<\/jats:italic>\n                      , which was reported to cause congenital hypogonadotropic hypogonadism (CHH), was identified in individuals with primary hypogonadism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      WES is a powerful tool to identify novel causal variants in patients with DSD, including a significant minority that have an atypical clinical presentation. Our data suggest that heterozygous variants in the\n                      <jats:italic>WDR11<\/jats:italic>\n                      gene are unlikely to cause of CHH.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2022.810782","type":"journal-article","created":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T02:30:54Z","timestamp":1648175454000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":51,"title":["Disorders of Sex Development in a Large Ukrainian Cohort: Clinical Diversity and Genetic 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