{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T14:16:32Z","timestamp":1761920192533,"version":"3.41.2"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,9,21]],"date-time":"2016-09-21T00:00:00Z","timestamp":1474416000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Beckwith\u2013Wiedemann syndrome (BWS) is an early\u2010onset overgrowth disorder with a high risk for embryonal tumors. It is mainly caused by dysregulation of imprinted genes on chromosome 11p15.5; however, the driving forces in the development of tumors are not fully understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>We report on a female patient presenting with macrosomia, macroglossia, organomegaly and extensive bilateral nephroblastomatosis. Adjuvant chemotherapy was initiated; however, the patient developed hepatoblastoma and Wilms tumor at 5 and 12 months of age, respectively. Subsequent radiofrequency ablation of the liver tumor and partial nephrectomy followed by consolidation therapy achieved complete remission.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Molecular genetic analysis revealed a maternally derived large deletion of the complete <jats:italic>H19<\/jats:italic>\u2010differentially methylated region (<jats:italic>H19<\/jats:italic>\u2010DMR; imprinting control region\u20101 [ICR1]), the whole <jats:italic>H19<\/jats:italic> gene itself as well as large parts of the distal enhancer region within the imprinting cluster\u20101 (IC1). Extended analysis showed highly elevated <jats:italic>insulin\u2010like growth factor 2 (IGF2)<\/jats:italic> expression, possibly explaining at least in part the distinct BWS features and tumor manifestations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study of a large maternal deletion encompassing the <jats:italic>H19<\/jats:italic> gene and complete ICR1 is the first to demonstrate transcriptional consequences on <jats:italic>IGF2<\/jats:italic> in addition to methylation effects resulting in severe overgrowth and occurrence of multiple tumors in a BWS patient. Studying this deletion helps to clarify the complex molecular processes involved in BWS and provides further insight into tumorigenesis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.26241","type":"journal-article","created":{"date-parts":[[2016,9,21]],"date-time":"2016-09-21T07:23:11Z","timestamp":1474442591000},"source":"Crossref","is-referenced-by-count":12,"title":["Novel deletion in 11p15.5 imprinting center region 1 in a patient with Beckwith\u2013Wiedemann syndrome provides insight into distal enhancer regulation and tumorigenesis"],"prefix":"10.1002","volume":"64","author":[{"given":"Nadine","family":"Bachmann","sequence":"first","affiliation":[{"name":"Center for Human Genetics Bioscientia  Ingelheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roman","family":"Crazzolara","sequence":"additional","affiliation":[{"name":"Department for Pediatrics Medical University Innsbruck  Innsbruck Austria"},{"name":"Tyrolean Cancer Research Institute  Innsbruck Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Bohne","sequence":"additional","affiliation":[{"name":"Center for Pediatrics and Adolescent Medicine Johannes Gutenberg University Medical Center  Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dieter","family":"Kotzot","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Medical University of Innsbruck  Innsbruck Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathrin","family":"Maurer","sequence":"additional","affiliation":[{"name":"Department for Pediatrics Medical University Innsbruck  Innsbruck Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thorsten","family":"Enklaar","sequence":"additional","affiliation":[{"name":"Center for Pediatrics and Adolescent Medicine Johannes Gutenberg University Medical Center  Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk","family":"Prawitt","sequence":"additional","affiliation":[{"name":"Center for Pediatrics and Adolescent Medicine Johannes Gutenberg University Medical Center  Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten","family":"Bergmann","sequence":"additional","affiliation":[{"name":"Center for Human Genetics Bioscientia  Ingelheim Germany"},{"name":"Department of Medicine University Hospital Freiburg  Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,9,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2009.106"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(98)70009-5"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.37.12.921"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200649"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.5.467"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.26.2989"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1086\/338934"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2004.08.007"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201463"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000355544"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2008.01.003"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1139\/o11-033"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu290"},{"volume-title":"GeneReviews(\u00ae) [Internet]","year":"1993","author":"Shuman C","key":"e_1_2_8_15_1"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1410"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl448"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2011.04.009"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds465"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1379-z"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp549"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21558"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0500037102"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2010.086504"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-015-0173-2"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001849"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.14.2200"},{"issue":"5","key":"e_1_2_8_28_1","first-page":"1205","article-title":"Novel conserved elements upstream of the H19 gene are transcribed and act as mesodermal enhancers","volume":"129","author":"Drewell RA","year":"2002","journal-title":"Dev Camb Engl"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.6.10.1843"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.02170-06"},{"issue":"6","key":"e_1_2_8_31_1","first-page":"1231","article-title":"Myod and H19\u2010Igf2 locus interactions are required for diaphragm formation in the mouse","volume":"140","author":"Borensztein M","year":"2013","journal-title":"Dev Camb Engl"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.2000.01438.x"},{"issue":"20","key":"e_1_2_8_33_1","first-page":"3413","article-title":"H19 acts as a trans regulator of the imprinted gene network controlling growth in mice","volume":"136","author":"Gabory A","year":"2009","journal-title":"Dev Camb Engl"}],"container-title":["Pediatric Blood &amp; Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpbc.26241","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpbc.26241","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.26241","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T17:15:06Z","timestamp":1696353306000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pbc.26241"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,9,21]]},"references-count":32,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2017,3]]}},"alternative-id":["10.1002\/pbc.26241"],"URL":"https:\/\/doi.org\/10.1002\/pbc.26241","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"type":"print","value":"1545-5009"},{"type":"electronic","value":"1545-5017"}],"subject":[],"published":{"date-parts":[[2016,9,21]]},"article-number":"e26241"}}