{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T08:17:54Z","timestamp":1790669874879,"version":"4.1.0"},"reference-count":46,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"vor","delay-in-days":365,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["CRU326"],"award-info":[{"award-number":["CRU326"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GRK1871\/2"],"award-info":[{"award-number":["GRK1871\/2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","fertstert.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Fertility and Sterility"],"published-print":{"date-parts":[[2023,2]]},"DOI":"10.1016\/j.fertnstert.2022.10.032","type":"journal-article","created":{"date-parts":[[2022,12,24]],"date-time":"2022-12-24T21:36:01Z","timestamp":1671917761000},"page":"219-228","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":13,"title":["Functional assessment of DMRT1 variants and their pathogenicity for isolated male infertility"],"prefix":"10.1016","volume":"119","author":[{"given":"Jana","family":"Emich","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avinash S.","family":"Gaikwad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Stallmeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Fietz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Christian","family":"Schuppe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon S.","family":"Oud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Kliesch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Gromoll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8848-3366","authenticated-orcid":false,"given":"Corinna","family":"Friedrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"T\u00fcttelmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.fertnstert.2022.10.032_bib1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12958-015-0032-1","article-title":"A unique view on male infertility around the globe","volume":"13","author":"Agarwal","year":"2015","journal-title":"Reprod Biol Endocrinol"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pmed.1001356","article-title":"National, regional, and global trends in infertility prevalence since 1990: a systematic analysis of 277 health surveys","volume":"9","author":"Mascarenhas","year":"2012","journal-title":"PLOS Med"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib3","unstructured":"World Health Organization. Laboratory manual for the examination and processing of human semen, 6th ed. Geneva:\u00a02021."},{"key":"10.1016\/j.fertnstert.2022.10.032_bib4","first-page":"12","article-title":"Disorders of spermatogenesis","volume":"30","author":"T\u00fcttelmann","year":"2018","journal-title":"Med Genet"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib5","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.urology.2010.10.001","article-title":"Role of genetics in azoospermia","volume":"77","author":"Lee","year":"2011","journal-title":"Urology"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib6","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1056\/NEJMoa1406192","article-title":"X-linked TEX11 mutations, meiotic arrest, and azoospermia in infertile men","volume":"372","author":"Yatsenko","year":"2015","journal-title":"N Engl J Med"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib7","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.ajhg.2018.07.005","article-title":"Bi-allelic recessive loss-of-function variants in FANCM cause non-obstructive azoospermia","volume":"103","author":"Kasak","year":"2018","journal-title":"Am J Hum Genet"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib8","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.ajhg.2020.06.010","article-title":"Bi-allelic mutations in M1AP are a frequent cause of meiotic arrest and severely impaired spermatogenesis leading to male infertility","volume":"107","author":"Wyrwoll","year":"2020","journal-title":"Am J Hum Genet"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib9","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/humupd\/dmab030","article-title":"A systematic review of the validated monogenic causes of human male infertility: 2020 update and a discussion of emerging gene\u2013disease relationships","volume":"28","author":"Houston","year":"2021","journal-title":"Hum Reprod Update"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib10","unstructured":"Wyrwoll MJ, K\u00f6ckerling N, Vockel M, Dicke A-K, Rotte N, Pohl E, et\u00a0al. Genetic architecture of azoospermia - time to advance the standard of care. Eur Urol. In press."},{"key":"10.1016\/j.fertnstert.2022.10.032_bib11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pgen.1003349","article-title":"Human spermatogenic failure purges deleterious mutation load from the autosomes and both sex chromosomes, including the gene DMRT1","volume":"9","author":"Lopes","year":"2013","journal-title":"PLoS Genet"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib12","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/j.fertnstert.2014.05.022","article-title":"DMRT1 mutations are rarely associated with male infertility","volume":"102","author":"Tewes","year":"2014","journal-title":"Fertil Steril"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib13","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1111\/andr.12063","article-title":"Rare double sex and mab-3-related transcription factor 1 regulatory variants in severe spermatogenic failure","volume":"3","author":"Lima","year":"2015","journal-title":"Andrology"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib14","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1038\/s41422-018-0099-2","article-title":"The adult human testis transcriptional cell atlas","volume":"28","author":"Guo","year":"2018","journal-title":"Cell Res"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib15","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1093\/molehr\/gas030","article-title":"Analysis of meiosis regulators in human gonads: a sexually dimorphic spatio-temporal expression pattern suggests involvement of DMRT1 in meiotic entry","volume":"18","author":"J\u00f8rgensen","year":"2012","journal-title":"Mol Hum Reprod"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib16","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":"Matson","year":"2010","journal-title":"Dev Cell"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib17","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/35618","article-title":"Evidence for evolutionary conservation of sex-determining genes","volume":"391","author":"Raymond","year":"1998","journal-title":"Nature"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib18","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.stem.2018.08.007","article-title":"Single-cell RNA sequencing analysis reveals sequential cell fate transition during human spermatogenesis","volume":"23","author":"Wang","year":"2018","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2199-8-58","article-title":"Vertebrate DM domain proteins bind similar DNA sequences and can heterodimerize on DNA","volume":"8","author":"Murphy","year":"2007","journal-title":"BMC Mol Biol"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib20","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/nsmb.3032","article-title":"An ancient protein-DNA interaction underlying metazoan sex determination","volume":"22","author":"Murphy","year":"2015","journal-title":"Nat Struct Mol Biol"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib21","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1093\/genetics\/94.2.383","article-title":"Sex and the single cell. I. on the action of major loci affecting sex determination in Drosophila melanogaster","volume":"94","author":"Baker","year":"1980","journal-title":"Genetics"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib22","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/0092-8674(88)90117-1","article-title":"Mab-3, a gene required for sex-specific yolk protein expression and a male-specific lineage in C. elegans","volume":"54","author":"Shen","year":"1988","journal-title":"Cell"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib23","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.1101\/gad.834100","article-title":"Dmrt1, a gene related to worm and fly sexual regulators, is required for mammalian testis differentiation","volume":"14","author":"Raymond","year":"2000","journal-title":"Genes Dev"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib24","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.ydbio.2007.04.046","article-title":"Cell type-autonomous and non-autonomous requirements for Dmrt1 in postnatal testis differentiation","volume":"307","author":"Kim","year":"2007","journal-title":"Dev Biol"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib25","first-page":"1083","article-title":"Female-to-male sex reversal in mice caused by transgenic overexpression of Dmrt1","volume":"142","author":"Zhao","year":"2015","journal-title":"Development"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib26","doi-asserted-by":"crossref","first-page":"2637","DOI":"10.1093\/humrep\/deq167","article-title":"Array-CGH analysis in patients with syndromic and non-syndromic XY gonadal dysgenesis: evaluation of array CGH as diagnostic tool and search for new candidate loci","volume":"25","author":"Ledig","year":"2010","journal-title":"Hum Reprod"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib27","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1530\/EJE-12-0136","article-title":"Partial deletion of DMRT1 causes 46, XY ovotesticular disorder of sexual development","volume":"167","author":"Ledig","year":"2012","journal-title":"Eur J Endocrinol"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib28","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1590\/S0004-27302010000800015","article-title":"Novel DMRT1 3\u2019UTR+11insT mutation associated to XY partial gonadal dysgenesis","volume":"54","author":"Mello","year":"2010","journal-title":"Arq Bras Endocrinol Metabol"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib29","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":"10.1016\/j.fertnstert.2022.10.032_bib30","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1038\/s41436-020-0907-1","article-title":"Genetic dissection of spermatogenic arrest through exome analysis: clinical implications for the management of azoospermic men","volume":"22","author":"Krausz","year":"2020","journal-title":"Genet Med"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib31","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1093\/humrep\/deab230","article-title":"Bi-allelic variants in DNA mismatch repair proteins MutS Homolog MSH4 and MSH5 cause infertility in both sexes","volume":"37","author":"Wyrwoll","year":"2021","journal-title":"Hum Reprod"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fcell.2021.658966","article-title":"TRIM71 deficiency causes germ cell loss during mouse embryogenesis and is associated with human male infertility","volume":"9","author":"Torres-Fernandez","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib33","first-page":"163","article-title":"Human INHBB gene variant (c.1079T>C:p.Met360Thr) alters testis germ cell\u00a0content, but does not impact fertility in mice","author":"Houston","year":"2022","journal-title":"Endocrinology"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib34","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1210\/en.2009-0999","article-title":"Doublesex- and Mab-3-related transcription factor-1 repression of aromatase transcription, a possible mechanism favoring the male pathway in Tilapia","volume":"151","author":"Wang","year":"2010","journal-title":"Endocrinology"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib35","first-page":"148","article-title":"Identification of regulatory elements required for Stra8 expression in fetal ovarian germ cells of the mouse","author":"Feng","year":"2021","journal-title":"Development"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib36","first-page":"321","article-title":"Genetic and clinical spectrum of aromatase deficiency in infancy, childhood and adolescence","volume":"72","author":"Belgorosky","year":"2009","journal-title":"Horm Res"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib37","doi-asserted-by":"crossref","first-page":"14976","DOI":"10.1073\/pnas.0807297105","article-title":"Stra8 and its inducer, retinoic acid, regulate meiotic initiation in both spermatogenesis and oogenesis in mice","volume":"105","author":"Anderson","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib38","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1002\/2211-5463.12035","article-title":"Sexually dimorphic expression of Dmrt1 and \u03b3H2AX in germ stem cells during gonadal development in Xenopus laevis","volume":"6","author":"Fujitani","year":"2016","journal-title":"FEBS Open Bio"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib39","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.1210\/js.2019-00306","article-title":"Next-generation sequencing reveals novel genetic variants (SRY, DMRT1, NR5A1, DHH, DHX37) in adults with 46,XY DSD","volume":"3","author":"Buonocore","year":"2019","journal-title":"J Endocr Soc"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib40","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":"10.1016\/j.fertnstert.2022.10.032_bib41","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1111\/andr.12704","article-title":"Sequence analysis of 37 candidate genes for male infertility: challenges\u00a0in variant assessment and validating genes","volume":"8","author":"Araujo","year":"2020","journal-title":"Andrology"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib42","doi-asserted-by":"crossref","first-page":"13360","DOI":"10.1073\/pnas.1006243107","article-title":"Genome-wide analysis of DNA binding and transcriptional regulation by the mammalian Doublesex homolog DMRT1 in the juvenile testis","volume":"107","author":"Murphy","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib43","doi-asserted-by":"crossref","DOI":"10.1016\/j.beem.2022.101633","article-title":"Genetics of 46,XY gonadal dysgenesis","volume":"36","author":"Elzaiat","year":"2022","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib44","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1038\/ejhg.2012.290","article-title":"Comprehensive sequence analysis of the NR5A1 gene encoding steroidogenic factor 1 in a large group of infertile males","volume":"21","author":"Ropke","year":"2013","journal-title":"Eur J Hum Genet"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib45","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1093\/hmg\/ddy037","article-title":"Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies","volume":"27","author":"Portnoi","year":"2018","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.fertnstert.2022.10.032_bib46","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.ajhg.2019.11.013","article-title":"SYCP2 translocation-mediated dysregulation and frameshift variants cause human male infertility","volume":"106","author":"Schilit","year":"2020","journal-title":"Am J Hum Genet"}],"container-title":["Fertility and Sterility"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0015028222019823?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0015028222019823?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T19:27:31Z","timestamp":1777404451000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0015028222019823"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2]]},"references-count":46,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["S0015028222019823"],"URL":"https:\/\/doi.org\/10.1016\/j.fertnstert.2022.10.032","relation":{},"ISSN":["0015-0282"],"issn-type":[{"value":"0015-0282","type":"print"}],"subject":[],"published":{"date-parts":[[2023,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Functional assessment of DMRT1 variants and their pathogenicity for isolated male infertility","name":"articletitle","label":"Article Title"},{"value":"Fertility and Sterility","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.fertnstert.2022.10.032","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a92022 American Society for Reproductive Medicine, Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}