{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T04:02:26Z","timestamp":1789358546147,"version":"build-2803163510"},"reference-count":8,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T00:00:00Z","timestamp":1789257600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T00:00:00Z","timestamp":1789257600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82501944"],"award-info":[{"award-number":["82501944"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Non\u2010obstructive azoospermia (NOA) represents the most severe form of male infertility, and the pathogenesis in partial patients can be attributed to endocrine dysfunction or heritable genetic variants. Although the application of whole\u2010exome sequencing (WES) has facilitated the identification of numerous pathogenic genes associated with NOA, the genetic etiology of a significant proportion of cases remains elusive. In this study, we identified an NOA patient carrying a novel variant in\n                    <jats:italic>DMRTB1<\/jats:italic>\n                    (c.792\u2013797del, p.265\u2013266del). The variant was rare in public databases and predicted to be likely pathogenic according to the American College of Medical Genetics (ACMG) guidelines. Structural modeling performed by SWISS\u2010MODEL revealed the localized structural perturbations within residues 254\u2013266, which may induce functional alterations. Histological analysis (H&amp;E staining) of the testicular tissue revealed a complete absence of mature sperm within the seminiferous tubules, which is consistent with the essential role of this gene demonstrated in Dmrt6 knockout mice. Our findings demonstrate that the identified\n                    <jats:italic>DMRTB1<\/jats:italic>\n                    variant is closely associated with the pathogenesis of NOA, thereby providing valuable genetic evidence for the diagnosis of NOA.\n                  <\/jats:p>","DOI":"10.1111\/cge.70243","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T03:07:00Z","timestamp":1789355220000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Homozygous Variant in\n                    <i>DMRTB1<\/i>\n                    Is Associated With Non\u2010Obstructive Azoospermia in Humans"],"prefix":"10.1111","author":[{"given":"YuHang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Andrology, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6518-9814","authenticated-orcid":false,"given":"Shuai","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Andrology, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Andrology, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1820-5270","authenticated-orcid":false,"given":"YiSong","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Andrology, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2901-3724","authenticated-orcid":false,"given":"HaoQiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Andrology, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Andrology, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Andrology, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0062-8434","authenticated-orcid":false,"given":"Qihan","family":"Chen","sequence":"additional","affiliation":[{"name":"Cancer Center, Faculty of Health Sciences University of Macau  Macau SAR China"},{"name":"Center of Precision Medicine Research and Training, Faculty of Health Sciences University of Macau  Macau SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6644-0461","authenticated-orcid":false,"given":"Ao","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Andrology, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6339-6355","authenticated-orcid":false,"given":"Xiaozhi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Andrology, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College Nanjing Medical University  Nanjing Jiangsu China"},{"name":"Department of Andrology, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,13]]},"reference":[{"issue":"7","key":"e_1_2_13_2_1","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/S2213-8587(16)30040-7","article-title":"Novel Concepts in the Aetiology of Male Reproductive Impairment","volume":"5","author":"Tournaye H.","year":"2017","journal-title":"Lancet Diabetes & Endocrinology"},{"issue":"1","key":"e_1_2_13_3_1","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1093\/humupd\/dmaa034","article-title":"Molecular Genetics of Infertility: Loss\u2010Of\u2010Function Mutations in Humans and Corresponding Knockout\/Mutated Mice","volume":"27","author":"Jiao S. Y.","year":"2021","journal-title":"Human Reproduction Update"},{"issue":"3","key":"e_1_2_13_4_1","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.ajhg.2022.01.011","article-title":"Whole\u2010Exome Sequencing Improves the Diagnosis and Care of Men With Non\u2010Obstructive Azoospermia","volume":"109","author":"Kherraf Z. E.","year":"2022","journal-title":"American Journal of Human Genetics"},{"issue":"14","key":"e_1_2_13_5_1","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1101\/gad.14.14.1750","article-title":"Sexual Dimorphism in Diverse Metazoans Is Regulated by a Novel Class of Intertwined Zinc Fingers","volume":"14","author":"Zhu L.","year":"2000","journal-title":"Genes & Development"},{"issue":"3","key":"e_1_2_13_6_1","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/nrg3161","article-title":"Sex and the Singular DM Domain: Insights Into Sexual Regulation, Evolution and Plasticity","volume":"13","author":"Matson C. K.","year":"2012","journal-title":"Nature Reviews. Genetics"},{"issue":"4","key":"e_1_2_13_7_1","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.devcel.2010.09.010","article-title":"The Mammalian Doublesex Homolog DMRT1 Is a Transcriptional Gatekeeper That Controls the Mitosis Versus Meiosis Decision in Male Germ Cells","volume":"19","author":"Ck M.","year":"2010","journal-title":"Developmental Cell"},{"issue":"19","key":"e_1_2_13_8_1","doi-asserted-by":"crossref","first-page":"3662","DOI":"10.1242\/dev.113936","article-title":"The Mammalian Doublesex Homolog DMRT6 Coordinates the Transition Between Mitotic and Meiotic Developmental Programs During Spermatogenesis","volume":"141","author":"Zhang T.","year":"2014","journal-title":"Development"},{"issue":"1","key":"e_1_2_13_9_1","doi-asserted-by":"crossref","DOI":"10.1007\/s11033-024-10006-9","article-title":"Diversity of Transactivation Regions of DMRT1 in Vertebrates","volume":"51","author":"Ishikawa N.","year":"2024","journal-title":"Molecular Biology Reports"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70243","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.70243","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70243","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T03:07:03Z","timestamp":1789355223000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.70243"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,13]]},"references-count":8,"alternative-id":["10.1111\/cge.70243"],"URL":"https:\/\/doi.org\/10.1111\/cge.70243","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,13]]},"assertion":[{"value":"2026-06-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"cge.70243"}}