{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:20:58Z","timestamp":1789172458711,"version":"build-2803163510"},"reference-count":37,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T00:00:00Z","timestamp":1682553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Brazilian National Council for Scientific and Technological Development (CNPq)","doi-asserted-by":"publisher","award":["406605\/2018-1"],"award-info":[{"award-number":["406605\/2018-1"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Brazilian National Council for Scientific and Technological Development (CNPq)","doi-asserted-by":"publisher","award":["FAPESP #2015\/04763-4"],"award-info":[{"award-number":["FAPESP #2015\/04763-4"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Brazilian National Council for Scientific and Technological Development (CNPq)","doi-asserted-by":"publisher","award":["FAPESP #2018\/19445-6"],"award-info":[{"award-number":["FAPESP #2018\/19445-6"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Brazilian National Council for Scientific and Technological Development (CNPq)","doi-asserted-by":"publisher","award":["FAPESP #2020\/01054-0"],"award-info":[{"award-number":["FAPESP #2020\/01054-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Brazilian National Council for Scientific and Technological Development (CNPq)","doi-asserted-by":"publisher","award":["#519.294"],"award-info":[{"award-number":["#519.294"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","award":["406605\/2018-1"],"award-info":[{"award-number":["406605\/2018-1"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","award":["FAPESP #2015\/04763-4"],"award-info":[{"award-number":["FAPESP #2015\/04763-4"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","award":["FAPESP #2018\/19445-6"],"award-info":[{"award-number":["FAPESP #2018\/19445-6"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","award":["FAPESP #2020\/01054-0"],"award-info":[{"award-number":["FAPESP #2020\/01054-0"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","award":["#519.294"],"award-info":[{"award-number":["#519.294"]}]},{"name":"Fundo de Apoio ao Ensino, \u00e0 Pesquisa e Extens\u00e3o","award":["406605\/2018-1"],"award-info":[{"award-number":["406605\/2018-1"]}]},{"name":"Fundo de Apoio ao Ensino, \u00e0 Pesquisa e Extens\u00e3o","award":["FAPESP #2015\/04763-4"],"award-info":[{"award-number":["FAPESP #2015\/04763-4"]}]},{"name":"Fundo de Apoio ao Ensino, \u00e0 Pesquisa e Extens\u00e3o","award":["FAPESP #2018\/19445-6"],"award-info":[{"award-number":["FAPESP #2018\/19445-6"]}]},{"name":"Fundo de Apoio ao Ensino, \u00e0 Pesquisa e Extens\u00e3o","award":["FAPESP #2020\/01054-0"],"award-info":[{"award-number":["FAPESP #2020\/01054-0"]}]},{"name":"Fundo de Apoio ao Ensino, \u00e0 Pesquisa e Extens\u00e3o","award":["#519.294"],"award-info":[{"award-number":["#519.294"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>The group of disorders known as 46,XY gonadal dysgenesis (GD) is characterized by anomalies in testis determination, including complete and partial GD (PGD) and testicular regression syndrome (TRS). Several genes are known to be involved in sex development pathways, however approximately 50% of all cases remain elusive. Recent studies have identified variants in DHX37, a gene encoding a putative RNA helicase essential in ribosome biogenesis and previously associated with neurodevelopmental disorders, as a cause of PGD and TRS. To investigate the potential role of DHX37 in disorders of sexual development (DSD), 25 individuals with 46,XY DSD were analyzed and putative pathogenic variants were found in four of them. WES analyses were performed on these patients. In DHX37, the variant p.(Arg308Gln), recurrent associated with DSD, was identified in one patient; the p.(Leu467Val), predicted to be deleterious, was found together with an NR5A1 loss-of-function variant in patient 2; and, the p.(Val999Met) was identified in two unrelated patients, one of whom (patient 3) also carried a pathogenic NR5A1 variant. For both patients carrying DHX37 and NR5A1 pathogenic variants, a digenic inheritance is suggested. Our findings support the importance of DHX37 variants as a cause of disorders of sex development, implying a role in testis development.<\/jats:p>","DOI":"10.3390\/life13051093","type":"journal-article","created":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T02:18:34Z","timestamp":1682561914000},"page":"1093","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["DHX37 and NR5A1 Variants Identified in Patients with 46,XY Partial Gonadal Dysgenesis"],"prefix":"10.3390","volume":"13","author":[{"given":"Felipe Rodrigues","family":"de Oliveira","sequence":"first","affiliation":[{"name":"Center for Molecular Biology and Genetic Engineering (CBMEG), State University of Campinas (UNICAMP), Campinas 13083-875, Brazil"},{"name":"Postgraduate Program in Child and Adolescent Health, School of Medical Sciences, State University of Campinas (UNICAMP), Campinas 13083-887, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ta\u00eds Nitsch","family":"Mazzola","sequence":"additional","affiliation":[{"name":"Center for Investigation in Paediatric, School of Medical Sciences, State University of Campinas (UNICAMP), Campinas 13083-887, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0521-9100","authenticated-orcid":false,"given":"Maricilda Palandi","family":"de Mello","sequence":"additional","affiliation":[{"name":"Center for Molecular Biology and Genetic Engineering (CBMEG), State University of Campinas (UNICAMP), Campinas 13083-875, Brazil"},{"name":"Interdisciplinary Group for the Study of Sex Determination and Differentiation (GIEDDS), State University of Campinas (UNICAMP), Campinas 13083-887, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Paula","family":"Francese-Santos","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, School of Medical Sciences, State University of Campinas (UNICAMP), Campinas 13083-887, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia Helena V. de","family":"Lemos-Marini","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medical Sciences, State University of Campinas (UNICAMP), Campinas 13083-887, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4850-8079","authenticated-orcid":false,"given":"Andrea Trevas","family":"Maciel-Guerra","sequence":"additional","affiliation":[{"name":"Interdisciplinary Group for the Study of Sex Determination and Differentiation (GIEDDS), State University of Campinas (UNICAMP), Campinas 13083-887, Brazil"},{"name":"Department of Translational Medicine, School of Medical Sciences, State University of Campinas (UNICAMP), Campinas 13083-887, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Hiort","sequence":"additional","affiliation":[{"name":"Division of Paediatric Endocrinology and Diabetes, Department of Paediatric and Adolescent Medicine, University of L\u00fcbeck, 23562 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3718-3595","authenticated-orcid":false,"given":"Ralf","family":"Werner","sequence":"additional","affiliation":[{"name":"Division of Paediatric Endocrinology and Diabetes, Department of Paediatric and Adolescent Medicine, University of L\u00fcbeck, 23562 L\u00fcbeck, Germany"},{"name":"Institute of Molecular Medicine, University of L\u00fcbeck, 23562 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gil","family":"Guerra-Junior","sequence":"additional","affiliation":[{"name":"Interdisciplinary Group for the Study of Sex Determination and Differentiation (GIEDDS), State University of Campinas (UNICAMP), Campinas 13083-887, Brazil"},{"name":"Department of Pediatrics, School of Medical Sciences, State University of Campinas (UNICAMP), Campinas 13083-887, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2738-1814","authenticated-orcid":false,"given":"Helena","family":"Fabbri-Scallet","sequence":"additional","affiliation":[{"name":"Center for Molecular Biology and Genetic Engineering (CBMEG), State University of Campinas (UNICAMP), Campinas 13083-875, Brazil"},{"name":"Interdisciplinary Group for the Study of Sex Determination and Differentiation (GIEDDS), State University of Campinas (UNICAMP), Campinas 13083-887, Brazil"},{"name":"Department of Translational Medicine, School of Medical Sciences, State University of Campinas (UNICAMP), Campinas 13083-887, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1542\/peds.2006-0738","article-title":"Consensus Statement on Management of Intersex Disorders","volume":"118","author":"Lee","year":"2006","journal-title":"Pediatrics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1159\/000442975","article-title":"Global Disorders of Sex Development Update since 2006: Perceptions, Approach and Care","volume":"85","author":"Lee","year":"2016","journal-title":"Horm. 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