{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T14:15:44Z","timestamp":1761920144249},"reference-count":13,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2016,5,25]],"date-time":"2016-05-25T00:00:00Z","timestamp":1464134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"BMBF","award":["01GM0886","01GM1114","01GM1513","RE 1723\/1-1"],"award-info":[{"award-number":["01GM0886","01GM1114","01GM1513","RE 1723\/1-1"]}]},{"name":"German Research Foundation (Deutsche Forschungsgemeinschaft, DFG)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The bladder exstrophy\u2010epispadias complex (BEEC) is characterized by a spectrum of genitourinary malformations. Both classical bladder exstrophy and the most severe phenotype, exstrophy of the cloaca, display omphaloceles, a cardinal anomaly of some disorders caused by altered imprinting. Therefore, we hypothesized that BEEC in some patients could occur on the basis of an undiagnosed imprinting disorder. Such altered imprinting is associated with changes in the parent\u2010of\u2010origin\u2010specific DNA methylation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed the DNA methylation of 54 imprinted loci in 23 selected patients with different BEEC subtypes (epispadias <jats:italic>n<\/jats:italic> = 1, classical bladder exstrophy <jats:italic>n<\/jats:italic> = 10, exstrophy of the cloaca <jats:italic>n<\/jats:italic> = 12) using the Infinium HumanMethylation450 BeadChip. A total of 471,722 not imprinted autosomal CpG loci and 891 imprinted CpG loci were investigated. Findings were corroborated by methylation\u2010specific\u2010multiplex ligation\u2010dependent probe amplification (MS\u2010MLPA) and microsatellite analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>No significant differences in the DNA methylation of the not imprinted and imprinted CpG were observed depending on subtype of BEEC. Nevertheless, in 1 of the 23 patients who displayed a classical bladder exstrophy, we detected hypomethylation of the imprinted <jats:italic>PLAGL1<\/jats:italic> locus in chromosome 6q24. We verified this hypomethylation by MS\u2010MLPA and showed further the methylation loss to be caused most likely by a mosaic epimutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Considering that it is highly unlikely to detect a <jats:italic>PLAGL1<\/jats:italic> epimutation among 23 individuals given the low incidence of this alteration in the population, our observations further support a link between BEEC and imprinting disorders. Birth Defects Research (Part A) 106:724\u2013728, 2016. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.23521","type":"journal-article","created":{"date-parts":[[2016,5,25]],"date-time":"2016-05-25T19:32:41Z","timestamp":1464204761000},"page":"724-728","source":"Crossref","is-referenced-by-count":2,"title":["<i>PLAGL1<\/i> epimutation and bladder exstrophy: Coincidence or concurrent etiology?"],"prefix":"10.1002","volume":"106","author":[{"given":"Julia","family":"Kolarova","sequence":"first","affiliation":[{"name":"Institute of Human Genetics Christian\u2010Albrechts\u2010University Kiel Kiel Germany"},{"name":"Institute of Human Genetics University of Ulm Ulm Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Bens","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics Christian\u2010Albrechts\u2010University Kiel Kiel Germany"},{"name":"Institute of Human Genetics University of Ulm Ulm Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ole","family":"Ammerpohl","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics Christian\u2010Albrechts\u2010University Kiel Kiel Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina C.","family":"Hilger","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heiko","family":"Reutter","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Bonn Bonn Germany"},{"name":"Department of Neonatology and Pediatric Intensive Care Children's Hospital, University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reiner","family":"Siebert","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics Christian\u2010Albrechts\u2010University Kiel Kiel Germany"},{"name":"Institute of Human Genetics University of Ulm Ulm Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,5,25]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20577"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki555"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201993"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201463"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.164913.113"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-4-23"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2015.05.001"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpurol.2015.05.030"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.27"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-005-0127-4"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/35047554"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.10058"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpurol.2006.10.007"}],"container-title":["Birth Defects Research Part A: Clinical and Molecular Teratology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbdra.23521","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdra.23521","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T07:58:52Z","timestamp":1695715132000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdra.23521"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,25]]},"references-count":13,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2016,8]]}},"alternative-id":["10.1002\/bdra.23521"],"URL":"https:\/\/doi.org\/10.1002\/bdra.23521","archive":["Portico"],"relation":{},"ISSN":["1542-0752","1542-0760"],"issn-type":[{"value":"1542-0752","type":"print"},{"value":"1542-0760","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,25]]}}}