{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T05:36:33Z","timestamp":1793424993689,"version":"4.5.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      46,XY disorders of sex development (DSD) is characterized by incomplete masculinization genitalia, with gonadal dysplasia and with\/without the presence of M\u00fcllerian structures. At least 30 genes related to 46,XY DSD have been found. However, the clinical phenotypes of patients with different gene mutations overlap, and accurate diagnosis relies on gene sequencing technology. Therefore, this study aims to determine the prevalence of pathogenic mutations in a Chinese cohort with 46,XY DSD by the targeted next-generation sequencing (NGS) technology. Eighty-seven 46,XY DSD patients were enrolled from the Peking Union Medical College Hospital (Beijing, China). A total of fifty-four rare variants were identified in 60 patients with 46,XY DSD. The incidence of these rare variants was approximately 69.0% (60\/87). Twenty-five novel variants and 29 reported variants were identified. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, thirty-three variants were classified as pathogenic or likely pathogenic variants and 21 variants were assessed as variants of uncertain significance. The overall diagnostic rate was about 42.5% based on the pathogenic and likely pathogenic variants. Androgen receptor (\n                      <jats:italic toggle=\"yes\">AR<\/jats:italic>\n                      ), steroid 5-alpha-reductase 2 (\n                      <jats:italic toggle=\"yes\">SRD5A2<\/jats:italic>\n                      ) and nuclear receptor subfamily 5 Group A member 1 (\n                      <jats:italic toggle=\"yes\">NR5A1<\/jats:italic>\n                      ) gene variants were identified in 21, 13 and 13 patients, respectively. The incidence of these three gene variants was about 78.3% (47\/60) in patients with rare variants. It is concluded that targeted NGS is an effective method to detect pathogenic mutations in 46,XY DSD patients and\n                      <jats:italic toggle=\"yes\">AR<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">SRD5A2<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">NR5A1<\/jats:italic>\n                      genes were the most common pathogenic genes in our cohort.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/aja.aja_36_20","type":"journal-article","created":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T04:13:19Z","timestamp":1601007199000},"page":"69-73","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":29,"title":["Prevalence of gene mutations in a Chinese 46,XY disorders of sex development cohort detected by targeted next-generation sequencing"],"prefix":"10.4103","volume":"23","author":[{"given":"Bing-Qing","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao-Xiang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin-Jie","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang-Feng","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Nie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Yan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-13-20240829","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1056\/NEJMra022784","article-title":"Sex determination and differentiation","volume":"350","author":"MacLaughlin","year":"2004","journal-title":"N Engl J Med"},{"key":"R2-13-20240829","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/nrendo.2014.163","article-title":"Genetic regulation of mammalian gonad development","volume":"10","author":"Eggers","year":"2014","journal-title":"Nat Rev Endocrinol"},{"key":"R3-13-20240829","doi-asserted-by":"crossref","first-page":"88","DOI":"10.2350\/12-04-1184-PB.1","article-title":"Perspectives in pediatric pathology, chapter 1.Normal development of testicular structures: from the bipotential gonad to the fetal testis","volume":"18","author":"Nistal","year":"2015","journal-title":"Pediatr Dev Pathol"},{"key":"R4-13-20240829","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.tig.2019.02.004","article-title":"Genetic control of gonadal sex determination and development","volume":"35","author":"Stevant","year":"2019","journal-title":"Trends Genet"},{"key":"R5-13-20240829","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.jpurol.2006.03.004","article-title":"Consensus statement on management of intersex disorders","volume":"2","author":"Hughes","year":"2006","journal-title":"J Pediatr Urol"},{"key":"R6-13-20240829","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/j.1365-2265.2008.03392.x","article-title":"46,XY disorders of sex development (DSD)","volume":"70","author":"Mendonca","year":"2009","journal-title":"Clin Endocrinol (Oxf"},{"key":"R7-13-20240829","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1530\/EC-18-0376","article-title":"Next generation sequencing (NGS) to improve the diagnosis and management of patients with disorders of sex development (DSD)","volume":"8","author":"Hughes","year":"2019","journal-title":"Endocr Connect"},{"key":"R8-13-20240829","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.mce.2017.01.037","article-title":"Diagnostic yield of targeted gene panel sequencing to identify the genetic etiology of disorders of sex development","volume":"444","author":"Kim","year":"2017","journal-title":"Mol Cell Endocrinol"},{"key":"R9-13-20240829","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1159\/000313372","article-title":"Difficulties in diagnosis and treatment of 5alpha-reductase type 2 deficiency in a newborn with 46,XY DSD","volume":"74","author":"Walter","year":"2010","journal-title":"Horm Res Paediatr"},{"key":"R10-13-20240829","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1586\/14737159.2015.976555","article-title":"Targeted next-generation sequencing panels for monogenetic disorders in clinical diagnostics: the opportunities and challenges","volume":"15","author":"de Koning","year":"2015","journal-title":"Expert Rev Mol Diagn"},{"key":"R11-13-20240829","doi-asserted-by":"crossref","first-page":"10846","DOI":"10.1038\/s41598-018-29263-3","article-title":"Coverage and diagnostic yield of whole exome sequencing for the evaluation of cases with dilated and hypertrophic cardiomyopathy","volume":"8","author":"Mak","year":"2018","journal-title":"Sci Rep"},{"key":"R12-13-20240829","doi-asserted-by":"crossref","first-page":"e0170843","DOI":"10.1371\/journal.pone.0170843","article-title":"Exome sequencing covers >98% of mutations identified on targeted next generation sequencing panels","volume":"12","author":"LaDuca","year":"2017","journal-title":"PLoS One"},{"key":"R13-13-20240829","doi-asserted-by":"crossref","first-page":"102033","DOI":"10.18632\/oncotarget.22116","article-title":"Development and validation of a targeted next generation DNA sequencing panel outperforming whole exome sequencing for the identification of clinically relevant genetic variants","volume":"8","author":"Miller","year":"2017","journal-title":"Oncotarget"},{"key":"R14-13-20240829","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1002\/humu.23114","article-title":"From wet-lab to variations: concordance and speed of bioinformatics pipelines for whole genome and whole exome sequencing","volume":"37","author":"Laurie","year":"2016","journal-title":"Hum Mutat"},{"key":"R15-13-20240829","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1111\/cen.13831","article-title":"Novel NR5A1 mutations found in Chinese patients with 46,XY disorders of sex development","volume":"89","author":"Yu","year":"2018","journal-title":"Clin Endocrinol (Oxf"},{"key":"R16-13-20240829","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.steroids.2017.07.009","article-title":"Novel mutations of HSD17B3 in three Chinese patients with 46,XY disorders of sex development","volume":"126","author":"Yu","year":"2017","journal-title":"Steroids"},{"key":"R17-13-20240829","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.gene.2012.03.029","article-title":"Detection of truncated dystrophin lacking the C-terminal domain in a Chinese pedigree by next-generation sequencing","volume":"499","author":"Xie","year":"2012","journal-title":"Gene"},{"key":"R18-13-20240829","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"R19-13-20240829","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/nrendo.2012.235","article-title":"Disorders of sex development: new genes, new concepts","volume":"9","author":"Ono","year":"2013","journal-title":"Nat Rev Endocrinol"},{"key":"R20-13-20240829","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/j.1399-0004.2012.01879.x","article-title":"Targeted massively parallel sequencing provides comprehensive genetic diagnosis for patients with disorders of sex development","volume":"83","author":"Arboleda","year":"2013","journal-title":"Clin Genet"},{"key":"R21-13-20240829","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/s00439-018-1879-y","article-title":"Next-generation sequencing reveals genetic landscape in 46,XY disorders of sexual development patients with variable phenotypes","volume":"137","author":"Wang","year":"2018","journal-title":"Hum Genet"},{"key":"R22-13-20240829","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1159\/000452995","article-title":"Rapid molecular genetic diagnosis with next-generation sequencing in 46,XY disorders of sex development cases: efficiency and cost assessment","volume":"87","author":"Ozen","year":"2017","journal-title":"Horm Res Paediatr"},{"key":"R23-13-20240829","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1186\/s13059-016-1105-y","article-title":"Disorders of sex development: insights from targeted gene sequencing of a large international patient cohort","volume":"17","author":"Eggers","year":"2016","journal-title":"Genome Biol"},{"key":"R24-13-20240829","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s12881-016-0286-2","article-title":"Targeted next-generation sequencing identification of mutations in patients with disorders of sex development","volume":"17","author":"Dong","year":"2016","journal-title":"BMC Med Genet"},{"key":"R25-13-20240829","doi-asserted-by":"crossref","first-page":"E333","DOI":"10.1210\/jc.2014-2605","article-title":"Exome sequencing for the diagnosis of 46,XY disorders of sex development","volume":"100","author":"Baxter","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"key":"R26-13-20240829","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1016\/j.ajhg.2010.11.003","article-title":"Mutations in MAP3K1 cause 46,XY disorders of sex development and implicate a common signal transduction pathway in human testis determination","volume":"87","author":"Pearlman","year":"2010","journal-title":"Am J Hum Genet"},{"key":"R27-13-20240829","doi-asserted-by":"crossref","first-page":"437","DOI":"10.4103\/0971-6866.124372","article-title":"Mutation analysis of mitogen activated protein kinase 1 gene in Indian cases of 46,XY disorder of sex development","volume":"19","author":"Das","year":"2013","journal-title":"Indian J Hum Genet"},{"key":"R28-13-20240829","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1111\/j.1399-0004.2011.01834.x","article-title":"Rapidly screening variants of uncertain significance in the MAP3K1 gene for phenotypic effects","volume":"81","author":"Loke","year":"2012","journal-title":"Clin Genet"},{"key":"R29-13-20240829","first-page":"2086861","article-title":"46,XY disorder of sex development caused by 17alpha-Hydroxylase\/17,20-Lyase deficiency due to homozygous mutation of CYP17A1 gene: consequences of late diagnosis","volume":"2018","author":"Papi","year":"2018","journal-title":"Case Rep Endocrinol"},{"key":"R30-13-20240829","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/S0889-8529(18)30101-4","article-title":"Disorders of steroid 17 alpha-hydroxylase deficiency","volume":"23","author":"Kater","year":"1994","journal-title":"Endocrinol Metab Clin North Am"},{"key":"R31-13-20240829","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1016\/j.juro.2014.06.040","article-title":"DNA copy number variations in patients with 46,XY disorders of sex development","volume":"192","author":"Harrison","year":"2014","journal-title":"J Urol"},{"key":"R32-13-20240829","doi-asserted-by":"crossref","first-page":"e17793","DOI":"10.1371\/journal.pone.0017793","article-title":"Copy number variation in patients with disorders of sex development due to 46,XY gonadal dysgenesis","volume":"6","author":"White","year":"2011","journal-title":"PLoS One"}],"container-title":["Asian Journal of Andrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/aja.aja_36_20","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T19:27:11Z","timestamp":1786735631000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/aja.aja_36_20"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021]]}},"URL":"https:\/\/doi.org\/10.4103\/aja.aja_36_20","relation":{},"ISSN":["1008-682X"],"issn-type":[{"value":"1008-682X","type":"print"}],"subject":[],"published":{"date-parts":[[2021,1]]}}}