{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T17:28:26Z","timestamp":1781890106881,"version":"3.54.5"},"reference-count":13,"publisher":"Walter de Gruyter GmbH","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,26]]},"abstract":"Abstract<\/jats:title>\n \n Objectives<\/jats:title>\n Here we present a case of 46,XY disorder of sex development (DSD) in which three variants were detected in the SRY<\/jats:italic>, DHX37<\/jats:italic>, and POR<\/jats:italic> genes.<\/jats:p>\n <\/jats:sec>\n \n Case presentation<\/jats:title>\n A patient with 46,XY karyotype and female phenotype presented at 15 years 3\u00a0months of age due to absence of puberty. She exhibited facial signs such as midfacial hypoplasia, long face, proptosis, bulbous nose, mild prognathism and skeletal signs such as scoliosis, pectus carinatum, arachnodactyly and her sex development remained prepubertal. The patient was found to have hypergonadotropic hypogonadism, elevation of 17-OH progesterone and progesterone levels, low anti-mullerian hormone and inhibin B levels, and absence of gonads and a hypoplastic uterus on pelvic ultrasound. Whole exome sequencing revealed a novel hemizygous missense variant in the SRY<\/jats:italic> gene (c.247C>T, p.Pro83Ser), a homozygous missense variant in the POR<\/jats:italic> gene (c.1355C>T, p.Pro452Leu), and a novel heterozygous missense variant in the DHX37<\/jats:italic> gene (c.1325A>G, p.His442Arg).<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Our patient is the first case in which the coexistence of variants in the SRY<\/jats:italic>, DHX37<\/jats:italic> and POR<\/jats:italic> genes was detected. This case suggests that a combined phenotype characterized by DSD and alterations in adrenal function may result from genetic variants in the SRY<\/jats:italic>, DHX37<\/jats:italic> and POR<\/jats:italic> genes involved in gonadal development and synthesis of adrenal hormones.<\/jats:p>\n <\/jats:sec>","DOI":"10.1515\/jpem-2024-0554","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T08:48:19Z","timestamp":1742460499000},"page":"658-662","source":"Crossref","is-referenced-by-count":3,"title":["Coexistence of SRY, DHX37<\/i> and POR<\/i> gene variants in a patient with 46,XY disorder of sex development"],"prefix":"10.1515","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3625-2387","authenticated-orcid":false,"given":"Ayse","family":"Ozden","sequence":"first","affiliation":[{"name":"Department of Pediatric Endocrinology, Faculty of Medicine , Ataturk University , Erzurum , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9774-3649","authenticated-orcid":false,"given":"Hakan","family":"Doneray","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Faculty of Medicine , Ataturk University , Erzurum , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9647-8970","authenticated-orcid":false,"given":"Ayberk","family":"Turkyilmaz","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics , Erzurum Regional Research and Training Hospital , Erzurum , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binali","family":"Firinci","sequence":"additional","affiliation":[{"name":"Department of Child Surgery, Faculty of Medicine , Ataturk University , Erzurum , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2025,3,21]]},"reference":[{"key":"2025053006390451440_j_jpem-2024-0554_ref_001","doi-asserted-by":"crossref","unstructured":"Elzaiat, M, McElreavey, K, Bashamboo, A. Genetics of 46,XY gonadal dysgenesis. Best Pract Res Clin Endocrinol Metabol 2022;36:101633. https:\/\/doi.org\/10.1016\/j.beem.2022.101633.","DOI":"10.1016\/j.beem.2022.101633"},{"key":"2025053006390451440_j_jpem-2024-0554_ref_002","doi-asserted-by":"crossref","unstructured":"De Oliveira, FR, Guaragna, MS, Maciel-Guerra, AT, Barros, BA, de Mello, MP, Guerra-Junior, G, et al.. DHX37 and the implications in disorders of sex development: an update review. Horm Res Paediatr 2023;23. https:\/\/doi.org\/10.1159\/000535969. Online ahead of print.","DOI":"10.1159\/000535969"},{"key":"2025053006390451440_j_jpem-2024-0554_ref_003","doi-asserted-by":"crossref","unstructured":"Rocha, VB, Guerra-J\u00fanior, G, Marques-de-Faria, AP, de Mello, MP, Maciel-Guerra, AT. Complete gonadal dysgenesis in clinical practice: the 46,XY karyotype accounts for more than one third of cases. Fertil Steril 2011;96:1431\u20134. https:\/\/doi.org\/10.1016\/j.fertnstert.2011.09.009.","DOI":"10.1016\/j.fertnstert.2011.09.009"},{"key":"2025053006390451440_j_jpem-2024-0554_ref_004","doi-asserted-by":"crossref","unstructured":"McElreavey, K, Pailhoux, E, Bashamboo, A. DHX37 and 46,XY DSD: a new ribosomopathy? Sex Dev 2022;16:194\u2013206. https:\/\/doi.org\/10.1159\/000522004.","DOI":"10.1159\/000522004"},{"key":"2025053006390451440_j_jpem-2024-0554_ref_005","doi-asserted-by":"crossref","unstructured":"Dean, B, Chrisp, GL, Quartararo, M, Maguire, AM, Hameed, S, King, BR, et al.. P450 oxidoreductase deficiency: a systematic review and meta-analysis of genotypes, phenotypes, and their relationships. J Clin Endocrinol Metab 2020;105:dgz255. https:\/\/doi.org\/10.1210\/clinem\/dgz255.","DOI":"10.1210\/clinem\/dgz255"},{"key":"2025053006390451440_j_jpem-2024-0554_ref_006","doi-asserted-by":"crossref","unstructured":"Wang, X, Xue, M, Zhao, M, He, F, Li, C, Li, X. Identification of a novel mutation (Ala66Thr) of SRY gene causes XY pure gonadal dysgenesis by affecting DNA binding activity and nuclear import. Gene 2018;651:143\u201351. https:\/\/doi.org\/10.1016\/j.gene.2018.01.076.","DOI":"10.1016\/j.gene.2018.01.076"},{"key":"2025053006390451440_j_jpem-2024-0554_ref_007","doi-asserted-by":"crossref","unstructured":"de Oliveira, FR, Mazzola, TN, de Mello, MP, Francese-Santos, AP, Lemos-Marini, SHV, Maciel-Guerra, AT, et al.. DHX37 and NR5A1 variants identified in patients with 46,XY partial gonadal dysgenesis. Life 2023;13:1093. https:\/\/doi.org\/10.3390\/life13051093.","DOI":"10.3390\/life13051093"},{"key":"2025053006390451440_j_jpem-2024-0554_ref_008","doi-asserted-by":"crossref","unstructured":"McElreavey, K, Jorgensen, A, Eozenou, C, Merel, T, Bignon-Topalovic, J, Tan, DS, et al.. Pathogenic variants in the DEAH-box RNA helicase DHX37 are a frequent cause of 46,XY gonadal dysgenesis and 46,XY testicular regression syndrome. Genet Med 2020;22:150\u20139. https:\/\/doi.org\/10.1038\/s41436-019-0606-y.","DOI":"10.1038\/s41436-019-0606-y"},{"key":"2025053006390451440_j_jpem-2024-0554_ref_009","doi-asserted-by":"crossref","unstructured":"da Silva, TE, Gomes, NL, Lerario, AM, Keegan, CE, Nishi, MY, Carvalho, FM, et al.. Genetic evidence of the association of DEAH-box helicase 37 defects with 46,XY gonadal dysgenesis spectrum. J Clin Endocrinol Metab 2019;104:5923\u201334. https:\/\/doi.org\/10.1210\/jc.2019-00984.","DOI":"10.1210\/jc.2019-00984"},{"key":"2025053006390451440_j_jpem-2024-0554_ref_010","doi-asserted-by":"crossref","unstructured":"Yang, H, Ma, X, Tian, H, Yuan, J, Wu, D, Dong, G. Two novel heterozygous variants in RecA2 domain of DHX37 cause 46,XY gonadal dysgenesis and testicular regression syndrome. Sex Dev 2023;17:198\u2013202. 202315.","DOI":"10.1159\/000534086"},{"key":"2025053006390451440_j_jpem-2024-0554_ref_011","doi-asserted-by":"crossref","unstructured":"Wan, Y, Yu, R, Luo, J, Huang, P, Zheng, X, Sun, L, et al.. A novel DEAH-box helicase 37 mutation associated with differences of sex development. Front Endocrinol 2023;14:1059159. https:\/\/doi.org\/10.3389\/fendo.2023.1059159.","DOI":"10.3389\/fendo.2023.1059159"},{"key":"2025053006390451440_j_jpem-2024-0554_ref_012","doi-asserted-by":"crossref","unstructured":"Huang, N, Agrawal, V, Giacomini, KM, Miller, WL. Genetics of P450 oxidoreductase: sequence variation in 842 individuals of four ethnicities and activities of 15 missense mutations. Proc Natl Acad Sci U. S. A 2008;105:1733\u20138. https:\/\/doi.org\/10.1073\/pnas.0711621105.","DOI":"10.1073\/pnas.0711621105"},{"key":"2025053006390451440_j_jpem-2024-0554_ref_013","doi-asserted-by":"crossref","unstructured":"Gusmano, C, Cannarella, R, Crafa, A, Barbagallo, F, La Vignera, S, Condorelli, RA, et al.. Congenital adrenal hyperplasia, disorders of sex development, and infertility in patients with POR gene pathogenic variants: a systematic review of the literat\u00fcre. 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