{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T17:44:38Z","timestamp":1770831878590,"version":"3.50.1"},"reference-count":24,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,4,25]],"date-time":"2014-04-25T00:00:00Z","timestamp":1398384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["RE 1723\/1-1"],"award-info":[{"award-number":["RE 1723\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Classic bladder exstrophy (CBE) is the most common form of the bladder exstrophy and epispadias complex. Previously, we and others have identified four patients with a duplication of 22q11.21 among a total of 96 unrelated CBE patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we investigated whether this chromosomal aberration was commonly associated with CBE\/bladder exstrophy and epispadias complex in an extended case\u2010control sample. Multiplex ligation\u2010dependent probe amplification and microarray\u2010based analysis were used to identify 22q11.21 duplications in 244 unrelated bladder exstrophy and epispadias complex patients (including 217 CBE patients) and 665 healthy controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>New duplications of variable size were identified in four CBE patients and one control. Pooling of our previous and present data (eight duplications in 313 CBE patients) yielded a combined odds ratio of 31.86 (95% confidence interval, 4.24\u20131407.97). Array\u2010based sequence capture and high\u2010throughput targeted re\u2010sequencing established that all breakpoints resided within the low\u2010copy repeats 22A to 22D. Comparison of the eight duplications revealed a 414 kb phenocritical region harboring 12 validated RefSeq genes. Characterization of these 12 candidate genes through whole\u2010mount in situ hybridization of mouse embryos at embryonic day 9.5 suggested that <jats:italic>CRKL<\/jats:italic>, <jats:italic>THAP7<\/jats:italic>, and <jats:italic>LZTR1<\/jats:italic> are CBE candidate genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data suggest that duplication of 22q11.21 increases CBE risk and implicate a phenocritical region in disease formation. <jats:italic>Birth Defects Research (Part A) 100:512\u2013517, 2014<\/jats:italic>. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.23249","type":"journal-article","created":{"date-parts":[[2014,4,25]],"date-time":"2014-04-25T05:24:41Z","timestamp":1398403481000},"page":"512-517","source":"Crossref","is-referenced-by-count":23,"title":["Classic bladder exstrophy: Frequent 22q11.21 duplications and definition of a 414 kb phenocritical region"],"prefix":"10.1002","volume":"100","author":[{"given":"Markus","family":"Draaken","sequence":"first","affiliation":[{"name":"Institute of Human Genetics University of Bonn Bonn Germany"},{"name":"Department of Genomics Life &amp; Brain Center University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Friederike","family":"Baudisch","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Bonn Bonn Germany"},{"name":"Department of Clinical Chemistry and Clinical Pharmacology University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernd","family":"Timmermann","sequence":"additional","affiliation":[{"name":"Next Generation Sequencing Group Max Planck Institute for Molecular Genetics Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heiner","family":"Kuhl","sequence":"additional","affiliation":[{"name":"Next Generation Sequencing Group Max Planck Institute for Molecular Genetics Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Kerick","sequence":"additional","affiliation":[{"name":"Next Generation Sequencing Group Max Planck Institute for Molecular Genetics Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith","family":"Proske","sequence":"additional","affiliation":[{"name":"Department of Developmental Genetics Max Planck Institute for Molecular Genetics Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Wittler","sequence":"additional","affiliation":[{"name":"Department of Developmental Genetics Max Planck Institute for Molecular Genetics Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracie","family":"Pennimpede","sequence":"additional","affiliation":[{"name":"Department of Developmental Genetics Max Planck Institute for Molecular Genetics Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne\u2010Karoline","family":"Ebert","sequence":"additional","affiliation":[{"name":"Department of Urology and Pediatric Urology University of Ulm Ulm Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"R\u00f6sch","sequence":"additional","affiliation":[{"name":"Department of Pediatric Urology St. Hedwig Hospital Barmherzige Br\u03bcder Regensburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raimund","family":"Stein","sequence":"additional","affiliation":[{"name":"Department of Urology University of Mainz Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrika","family":"Bartels","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catharina","family":"von Lowtzow","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Bonn Bonn Germany"},{"name":"Department of Genomics Life &amp; Brain Center University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas M.","family":"Boemers","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery and Pediatric Urology Children's Hospital Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Herms","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Bonn Bonn Germany"},{"name":"Department of Genomics Life &amp; Brain Center University of Bonn Bonn Germany"},{"name":"Division of Medical Genetics and Department of Biomedicine University of Basel Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John P.","family":"Gearhart","sequence":"additional","affiliation":[{"name":"Division of Urology The James Buchanan Brady Urological Institute Johns Hopkins University School of Medicine Baltimore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yegappan","family":"Lakshmanan","sequence":"additional","affiliation":[{"name":"Children's Hospital of Michigan Department of Pediatric Urology Detroit Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina Clementsson","family":"Kockum","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery University Hospital Lund Lund Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gundela","family":"Holmdahl","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Queen Silvia Children's Hospital Gothenburg Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00f6ran","family":"L\u00e4ckgren","sequence":"additional","affiliation":[{"name":"Section of Urology Uppsala Academic Children Hospital Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnetha","family":"Nordenskj\u00f6ld","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health Center for Molecular Medicine Karolinska Institute Stockholm Sweden"},{"name":"Department of Pediatric Surgery Astrid Lindgren Children's Hospital Karolinska University Hospital Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simeon A.","family":"Boyadjiev","sequence":"additional","affiliation":[{"name":"Section of Genetics Department of Pediatrics University of California Davis Sacramento California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernhard G.","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Department of Developmental Genetics Max Planck Institute for Molecular Genetics Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus M.","family":"N\u00f6then","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Bonn Bonn Germany"},{"name":"Department of Genomics Life &amp; Brain Center University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Clinical Pharmacology 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 Children's Hospital University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,4,25]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2007.09.014"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1211"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2009.12.005"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-4-23"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.7.1157"},{"key":"e_1_2_6_7_1","first-page":"1993","volume-title":"GeneReviews\u2122[Internet]","author":"Firth HV","year":"2013"},{"key":"e_1_2_6_8_1","first-page":"2136","volume-title":"Campbell's urology","author":"Gearhart JP","year":"2002"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1104935"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(82)80116-9"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2009.11.004"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0040086"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2007101078"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-6-9"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2012.09.003"},{"issue":"1","key":"e_1_2_6_16_1","first-page":"89","article-title":"22q11.2 microduplication in a patient with bladder exstrophy and delayed psychomotor development","volume":"20","author":"Pierquin G","year":"2012","journal-title":"Eur J Hum Genet"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2009.02.008"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23161"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.34.1.297"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.5986507"},{"key":"e_1_2_6_21_1","first-page":"56","article-title":"A new syndrome involving cleft palate, cardiac anomalies, typical facies, and learning disabilities: velo\u2010cardio\u2010facial syndrome","volume":"15","author":"Shprintzen RJ","year":"1978","journal-title":"Cleft Palate J"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33802"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh029"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003070"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)64215-2"}],"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.23249","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdra.23249","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T10:28:59Z","timestamp":1696588139000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdra.23249"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,4,25]]},"references-count":24,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2014,6]]}},"alternative-id":["10.1002\/bdra.23249"],"URL":"https:\/\/doi.org\/10.1002\/bdra.23249","archive":["Portico"],"relation":{},"ISSN":["1542-0752","1542-0760"],"issn-type":[{"value":"1542-0752","type":"print"},{"value":"1542-0760","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,4,25]]}}}