{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T03:28:46Z","timestamp":1747193326326,"version":"3.40.5"},"reference-count":19,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sex Dev"],"published-print":{"date-parts":[[2015]]},"abstract":"<i>MAMLD1<\/i> is a causative gene for disorders of sex development. Several <i>MAMLD1<\/i> mutations have been shown to cause hypospadias by generating dysfunctional proteins and\/or unstable mRNAs. Here, we identified an intronic mutation of <i>MAMLD1<\/i> (g.IVS4\u22122A>G) in 1 of 180 hypospadias patients. RT-PCR of the patient's skin sample showed normal expression of full-length<i> MAMLD1<\/i> and markedly reduced expression of a known splice variant lacking exon 4. A hitherto unreported splice variant that lacks exon 5 was similarly identified in samples of the patient and control individuals. The full-length transcript of the patient contained mutant mRNA lacking the first 10 nucleotides of exon 5 (c.1822_1831delACTCATGTAG, p.K609fsX1070). In vitro assays using cells expressing the full-length wild-type and mutant proteins revealed reduced expression of the mutant. The expression of the wild-type and mutant MAMLD1 showed parallel changes upon treatment with a proteasome inhibitor and a translation inhibitor. The mutant-expressing cells exerted low transactivation activity for the <i>Hes3<\/i> promoter, which reflected limited expression of the mutant protein. These results imply that the pathogenic events resulting from <i>MAMLD1<\/i> mutations include splice errors. Furthermore, this study raises the possibility of translation failure of MAMLD1 mutants, which deserves further investigation.<\/jats:p>","DOI":"10.1159\/000380842","type":"journal-article","created":{"date-parts":[[2015,4,1]],"date-time":"2015-04-01T12:49:16Z","timestamp":1427892556000},"page":"130-135","source":"Crossref","is-referenced-by-count":13,"title":["Novel Splice Site Mutation in MAMLD1 in a Patient with Hypospadias"],"prefix":"10.1159","volume":"9","author":[{"given":"Maki","family":"Igarashi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuka","family":"Wada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiyuki","family":"Kojima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mami","family":"Miyado","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michiko","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Muroya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kentaro","family":"Mizuno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutaro","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsuya","family":"Nonomura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenjiro","family":"Kohri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsutomu","family":"Ogata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9971-4035","authenticated-orcid":false,"given":"Maki","family":"Fukami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2015,3,31]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.154575"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2010.03.005"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(20000228)90:5<398::AID-AJMG10>3.3.CO;2-Z"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1038\/ng1900"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M703289200"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006361"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-08-0085"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpurol.2011.09.005"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032505"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2009.200"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2006.05.005"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1997.4662"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.087114"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1186\/1752-1947-6-428"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1210\/en.2012-1324"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1101\/gr.118638.110"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2004.12.005"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1002\/path.2649"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12072"}],"container-title":["Sexual Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/380842","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/380842","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T17:47:10Z","timestamp":1745430430000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000380842"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015]]},"references-count":19,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2015,8,1]]},"published-print":{"date-parts":[[2015,8,6]]}},"URL":"https:\/\/doi.org\/10.1159\/000380842","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.5127763","asserted-by":"subject"}]},"ISSN":["1661-5425","1661-5433"],"issn-type":[{"type":"print","value":"1661-5425"},{"type":"electronic","value":"1661-5433"}],"subject":[],"published":{"date-parts":[[2015]]}}}