{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T05:37:14Z","timestamp":1791005834575,"version":"4.1.0"},"reference-count":16,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T00:00:00Z","timestamp":1684454400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971375"],"award-info":[{"award-number":["81971375"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7212080"],"award-info":[{"award-number":["7212080"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7202151"],"award-info":[{"award-number":["7202151"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>The etiology of 46, XY disorders of sex development (46, XY DSD) is complex, and studies have shown that different series of patients with 46, XY DSD has different genetic spectrum. In this study, we aimed to investigate the underlying genetic etiology in a Chinese series of patients with 46, XY DSD by whole exome sequencing (WES).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Seventy patients with 46, XY DSD were enrolled from the Peking Union Medical College Hospital (Beijing, China). The detailed clinical characteristics were evaluated, and peripheral blood was collected for WES to find the patients\u2019 rare variants (RVs) of genes related to 46, XY DSD. The clinical significance of the RVs was annotated according to American College of Medical Genetics and Genomics (ACMG) guidelines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 57 RVs from nine genes were identified in 56 patients with 46, XY DSD, which include 21 novel RVs and 36 recurrent RVs. Based on the American ACMG guidelines, 43 variants were classified as pathogenic(P) or likely pathogenic (LP) variants and 14 variants were defined as variants of uncertain significance (VUS). P or LP variants were identified in 64.3% (45\/70) patients of the series. Thirty\u2010nine, 14, and 4 RVs were involved in the process of androgen synthesis and action, testicular determination and developmental process, and syndromic 46, XY DSD, respectively. The top three genes most frequently affected to cause 46, XY DSD were AR, SRD5A2, and NR5A1. Seven patients were found harboring RVs of the 46, XY DSD pathogenic genes identified in recent years, namely <jats:italic>DHX37<\/jats:italic> in four patients, <jats:italic>MYRF<\/jats:italic> in two patients, and <jats:italic>PPP2R3C<\/jats:italic> in one patient.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We identified 21 novel RVs of nine genes, which extended the genetic spectrum of 46, XY DSD pathogenic variants. Our study showed that 60% of the patients were caused by <jats:italic>AR<\/jats:italic>, <jats:italic>SRD5A2<\/jats:italic> or <jats:italic>NR5A1<\/jats:italic> P\/LP variants. Therefore, polymerase chain reaction (PCR) amplification and Sanger sequencing of these three genes could be performed first to identify the pathogeny of the patients. For those patients whose pathogenic variants had not been found, whole\u2010exome sequencing could be helpful in determining the etiology.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.13446","type":"journal-article","created":{"date-parts":[[2023,5,6]],"date-time":"2023-05-06T07:09:36Z","timestamp":1683356976000},"page":"98-108","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The genetic spectrum of a Chinese series of patients with 46, XY disorders of the sex development"],"prefix":"10.1111","volume":"12","author":[{"given":"Wei","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Endocrinology NHC Key laboratory of Endocrinology (Peking Union Medical College Hospital) Peking Union Medical College Peking Union Medical College Hospital Chinese Academy of Medical Sciences  Beijing 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Union Medical College Hospital Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology NHC Key laboratory of Endocrinology (Peking Union Medical College Hospital) Peking Union Medical College Peking Union Medical College Hospital Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Endocrinology NHC Key laboratory of Endocrinology (Peking Union Medical College Hospital) Peking Union Medical College Peking Union Medical College Hospital Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqing","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology NHC Key laboratory of Endocrinology 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