{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:46:07Z","timestamp":1790711167292,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T00:00:00Z","timestamp":1737936000000},"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"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>46,XY differences\/disorders of sex development (DSD) are genetically heterogeneous conditions characterized by atypical development of the reproductive system. <jats:italic>MYRF<\/jats:italic>, a gene encoding a transcription factor, has been identified as a potential causative gene for DSD and cardiac urogenital syndrome (CUGS). This study aims to delineate the clinical manifestations of patients with 46,XY DSD and <jats:italic>MYRF<\/jats:italic> mutations, encompassing both from our cohort and cases reported in the literature. Patients with 46,XY DSD were recruited from Peking Union Medical College Hospital and identified through a comprehensive review of published literature. Whole\u2010exome sequencing was conducted to elucidate the genetic etiology. Comprehensive clinical data, including physical examination findings, hormonal profiles, and imaging results, were retrospectively gathered from medical records and published sources. Three of our patients with 46,XY DSD were found to harbor heterozygous loss\u2010of\u2010function mutations in the <jats:italic>MYRF<\/jats:italic> gene, including the recurrent variant c.789dup and two novel variants c.1915C&gt;T and c.2154del. The patients exhibited underdeveloped testicular tissue, inadequate masculinization, and the persistence of M\u00fcllerian ducts. A review of the literature indentified 31 MYRF\u2010linked 46,XY DSD patients and two 46,XX DSD patients. Among these, 11 cases presented with isolated testicular dysgenesis, 20 cases exhibited severe cardiopulmonary issues, and the majority of patients had congenital diaphragmatic hernia. Genetic analysis revealed 26 distinct <jats:italic>MYRF<\/jats:italic> variants among these patients, including 10 missense, 8 frameshift, 5 nonsense, and 3 splice site alterations, affecting critical domains of the <jats:italic>MYRF<\/jats:italic> gene. Our study broadens the spectrum of <jats:italic>MYRF<\/jats:italic> mutations in 46,XY DSD patients and highlighting the gene's indispensable role in gonadal development. However, a clear genotype\u2013phenotype correlation in MYRF\u2010related DSD remain elusive.<\/jats:p>","DOI":"10.1002\/ajmg.a.64002","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T12:21:43Z","timestamp":1737980503000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>MYRF<\/scp> Variants in Patients With 46,<scp>XY<\/scp> Differences\/Disorders of Sex Development and Literature Review"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5939-1574","authenticated-orcid":false,"given":"Wei","family":"Zhang","sequence":"first","affiliation":[{"name":"NHC Key Laboratory of Endocrinology (Peking Union Medical College Hospital), Department of Endocrinology Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Wang","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Endocrinology (Peking Union Medical College Hospital), Department of Endocrinology Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangfeng","family":"Mao","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Endocrinology (Peking Union Medical College Hospital), Department of Endocrinology Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqing","family":"Cao","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Endocrinology (Peking Union Medical College Hospital), Department of Endocrinology Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxia","family":"Zhang","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Endocrinology (Peking Union Medical College Hospital), Department of Endocrinology Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7179-0044","authenticated-orcid":false,"given":"Min","family":"Nie","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Endocrinology (Peking Union Medical College Hospital), Department of Endocrinology Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9369-8430","authenticated-orcid":false,"given":"Xueyan","family":"Wu","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Endocrinology (Peking Union Medical College Hospital), Department of Endocrinology Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,27]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001625"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11164858"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.40360"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm13071158"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(200001)15:1<7::AID-HUMU4>3.0.CO;2-N"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.04.031"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008130"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.810782"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.18-26275"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62744"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddz066"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3970"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38620"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007822"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-021-01139-4"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61182"},{"key":"e_1_2_12_18_1","first-page":"527","article-title":"Autosomal Dominant Nanophthalmos and High Hyperopia Associated With a C\u2010Terminal Frameshift Variant in MYRF","volume":"25","author":"Siggs O. 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