{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T18:08:26Z","timestamp":1787681306935,"version":"build-2784847793"},"reference-count":21,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,3,16]],"date-time":"2014-03-16T00:00:00Z","timestamp":1394928000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"crossref","award":["166408"],"award-info":[{"award-number":["166408"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Inactivating mutations of the 5<jats:italic>\u03b1<\/jats:italic>\u2010steroid reductase type\u20102 (<jats:italic><jats:styled-content style=\"fixed-case\">SRD<\/jats:styled-content>5A2<\/jats:italic>) gene result in a broad spectrum of masculinization defects, ranging from a male phenotype with hypospadias to a female phenotype with Wolffian structures. Molecular studies of the <jats:italic><jats:styled-content style=\"fixed-case\">SRD<\/jats:styled-content>5A2<\/jats:italic> revealed a new heterozygous gene variant within the coding region that results in phenotypic expression. A c.92C&gt;T transition changing serine to phenylalanine at codon 31 of exon 1 (p.Ser31Phe) was identified in a patient with 46,XY disorder of sexual development who displayed glandular hypospadias with micropenis and bilateral cryptorchidism. The restoration of the p.Ser31Phe mutation by site\u2010directed mutagenesis and transient expression assays using cultured <jats:styled-content style=\"fixed-case\">HEK<\/jats:styled-content>\u2010293 cells showed that this novel substitution does not abolish but does deregulate the catalytic efficiency of the enzyme. Thus, the maximum velocity (<jats:italic>V<\/jats:italic><jats:sub>max<\/jats:sub>) value was higher for the mutant enzyme (22.5\u00a0\u00b1\u00a06.9\u00a0nmol DHT mg protein<jats:sup>\u22121<\/jats:sup> h<jats:sup>\u22121<\/jats:sup>) than for the wild\u2010type enzyme (9.8\u00a0\u00b1\u00a02.0\u00a0nmol DHT mg protein<jats:sup>\u22121<\/jats:sup> h<jats:sup>\u22121<\/jats:sup>). Increased in vitro activity of the p.Ser31Phe mutant suggested an activating effect. This case provides evidence that heterozygous missense mutations in <jats:italic><jats:styled-content style=\"fixed-case\">SRD<\/jats:styled-content>5A2<\/jats:italic> may induce the abnormal development of male external genitalia.<\/jats:p>","DOI":"10.1002\/mgg3.76","type":"journal-article","created":{"date-parts":[[2014,3,17]],"date-time":"2014-03-17T04:14:51Z","timestamp":1395029691000},"page":"292-296","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["46,XY disorder of sexual development resulting from a novel monoallelic mutation (p.Ser31Phe) in the steroid 5<i>\u03b1<\/i>\u2010reductase type\u20102 (<i>SRD5A2<\/i>) gene"],"prefix":"10.1002","volume":"2","author":[{"given":"Bertha","family":"Ch\u00e1vez","sequence":"first","affiliation":[{"name":"Department of Reproductive Biology Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n S. Z. M\u00e9xico City M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Ramos","sequence":"additional","affiliation":[{"name":"Department of Reproductive Biology Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n S. Z. M\u00e9xico City M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"G\u00f3mez","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology Medical Research Unit Hospital de Especialidades, CMN Siglo XXI, Instituto Mexicano del Seguro Social M\u00e9xico City M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Vilchis","sequence":"additional","affiliation":[{"name":"Department of Reproductive Biology Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n S. Z. M\u00e9xico City M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,3,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011\u20103169"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.1997.800904.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2013.04.002"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.85.9.3147"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3389fendo.2013.0019"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.2010.01136.x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-09-0067"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-1024"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207922"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2009.11.003"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2005.02348.x"},{"key":"e_1_2_8_13_1","first-page":"275","article-title":"The molecular genetics of steroid 5\u03b1\u2010reductases","volume":"49","author":"Russell D. 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