{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:28:30Z","timestamp":1790616510649,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T00:00:00Z","timestamp":1574380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["88881.186971\/2018\u201001"],"award-info":[{"award-number":["88881.186971\/2018\u201001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"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"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The routine genetic analysis for diagnosing male infertility has not changed over the last twenty years, and currently available tests can only determine the etiology of 4% of unselected infertile patients. Thus, to create new diagnostic assays, we must better understand the molecular and genetic mechanisms of male infertility. Although next\u2010generation sequencing allows for simultaneous analysis of hundreds of genes and the discovery of novel candidates related to male infertility, so far only a few gene candidates have enough sound evidence to support the gene\u2013disease relationship.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>Since complementary studies are required to validate genes<jats:italic>,<\/jats:italic> we aimed to analyze the presence of potentially pathogenic rare variants in a set of candidate genes related to azoospermia in a hitherto understudied South American population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Subjects and Methods<\/jats:title><jats:p>We performed whole exome sequencing in a group of 16 patients with non\u2010obstructive azoospermia from Ribeir\u00e3o Preto, Brazil. Based on a recent systematic review of monogenic causes of male infertility, we selected a set of 37 genes related to azoospermia, Sertoli\u2010Cell\u2010Only histology, and spermatogenic arrest to analyze. The identified variants were confirmed by Sanger sequencing, and their functional consequence was predicted by <jats:italic>in silico<\/jats:italic> programs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified potential pathogenic variants in seven genes in six patients. Two variants, c.671A&gt;G (p.(Asn224Ser)) in <jats:italic><jats:styled-content style=\"fixed-case\">DMRT<\/jats:styled-content>1<\/jats:italic> and c.91C&gt;T (p.(Arg31Cys)) in <jats:italic><jats:styled-content style=\"fixed-case\">REC<\/jats:styled-content>8<\/jats:italic>, have already been described in association with azoospermia. We also found new variants in genes that already have moderate evidence of being linked to spermatogenic failure (<jats:italic><jats:styled-content style=\"fixed-case\">TEX<\/jats:styled-content>15, <jats:styled-content style=\"fixed-case\">KLHL<\/jats:styled-content>10<\/jats:italic>), in genes with limited evidence (<jats:italic><jats:styled-content style=\"fixed-case\">DNMT<\/jats:styled-content>3B, <jats:styled-content style=\"fixed-case\">TEX<\/jats:styled-content>14<\/jats:italic>) and in one novel promising candidate gene that has no evidence so far (<jats:italic><jats:styled-content style=\"fixed-case\">SYCE<\/jats:styled-content>1L<\/jats:italic>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Although this study included a small number of patients, the process of rationally selecting genes allowed us to detect rare potentially pathogenic variants, providing supporting evidence for validating candidate genes associated with azoospermia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.12704","type":"journal-article","created":{"date-parts":[[2019,9,3]],"date-time":"2019-09-03T19:49:56Z","timestamp":1567540196000},"page":"434-441","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Sequence analysis of 37 candidate genes for male infertility: challenges in variant assessment and validating genes"],"prefix":"10.1111","volume":"8","author":[{"given":"T. F.","family":"Araujo","sequence":"first","affiliation":[{"name":"Department of Genetics Ribeir\u00e3o Preto Medical School University of S\u00e3o Paulo (USP) Ribeir\u00e3o Preto SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Friedrich","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of M\u00fcnster M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. H. P.","family":"Grangeiro","sequence":"additional","affiliation":[{"name":"Department of Genetics Ribeir\u00e3o Preto Medical School University of S\u00e3o Paulo (USP) Ribeir\u00e3o Preto SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. R.","family":"Martelli","sequence":"additional","affiliation":[{"name":"Department of Genetics Ribeir\u00e3o Preto Medical School University of S\u00e3o Paulo (USP) Ribeir\u00e3o Preto SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. D.","family":"Grzesiuk","sequence":"additional","affiliation":[{"name":"Department of Genetics Ribeir\u00e3o Preto Medical School University of S\u00e3o Paulo (USP) Ribeir\u00e3o Preto SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Emich","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of M\u00fcnster M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. J.","family":"Wyrwoll","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of M\u00fcnster M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Kliesch","sequence":"additional","affiliation":[{"name":"Centre of Reproductive Medicine and Andrology Department of Clinical and Surgical Andrology University Hospital M\u00fcnster M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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