{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T02:25:33Z","timestamp":1794018333229,"version":"4.8.0"},"reference-count":15,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":175,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24ek0109760"],"award-info":[{"award-number":["JP24ek0109760"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24ck0106990"],"award-info":[{"award-number":["JP24ck0106990"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["25K19217"],"award-info":[{"award-number":["25K19217"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Congenital Anomalies"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Rubinstein\u2013Taybi syndrome (RTS) is caused by germline loss\u2010of\u2010function variants of\n                    <jats:italic>CREBBP<\/jats:italic>\n                    or\n                    <jats:italic>EP300<\/jats:italic>\n                    , which function as histone acetyltransferases and act as tumor suppressors. Various benign or malignant tumors have been reported in RTS, suggesting tumor predisposition. To date, five patients with RTS complicated by neuroblastoma have been reported, and pathogenic germline variants were confirmed in two of the patients. We report a 2\u2010year\u2010old male with neuroblastoma and RTS harboring a germline\n                    <jats:italic>CREBBP<\/jats:italic>\n                    missense variant at the histone acetyltransferase (HAT) domain. Neuroblastoma was diagnosed at 4\u2009months of age, and histological evaluation classified the tumor as low risk. The neuroblastoma was stable at 2\u2009years of age. His dysmorphic features and developmental delay were consistent with phenotypes of RTS. Whole genome sequencing of both tumor and germline identified a de novo missense variant of\n                    <jats:italic>CREBBP<\/jats:italic>\n                    (NM_004380.3:c.4862T&gt;A p.(Leu1621Gln)). No other contributing germline or somatic variants were identified, except for polyploidy involving chromosomes 7, 12, and 17. Our results suggest that germline loss\u2010of\u2010function of\n                    <jats:italic>CREBBP<\/jats:italic>\n                    may contribute to tumor predisposition factor since somatic variants of\n                    <jats:italic>CREBBP<\/jats:italic>\n                    and\n                    <jats:italic>EP300<\/jats:italic>\n                    have been identified in neuroblastoma. Paired tumor\u2010normal genome sequencing enabled comprehensive analysis of germline tumor predisposition, as well as genomic profiles of tumor tissue.\n                  <\/jats:p>","DOI":"10.1002\/cga.70068","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T16:00:56Z","timestamp":1782403256000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multifocal Neuroblastoma in Rubinstein\u2013Taybi Syndrome Harboring a Novel\n                    <scp>\n                      <i>CREBBP<\/i>\n                    <\/scp>\n                    Variant Identified by Paired Whole Genome Sequencing"],"prefix":"10.1002","volume":"66","author":[{"given":"Yuki","family":"Fushimi","sequence":"first","affiliation":[{"name":"Division of Medical Genetics Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Kawai","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dai","family":"Keino","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mio","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Pathology Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naruto","family":"Takuya","sequence":"additional","affiliation":[{"name":"Clinical Research Institute, Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Sekiguchi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Graduate School of Medicine, the University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5145-1774","authenticated-orcid":false,"given":"Motohiro","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Graduate School of Medicine, the University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Kuroda","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399407000415"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0168\u20109525(98)01438\u20103"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12887\u2010025\u201005608\u20106"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36399"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19990423)83:5<365::AID-AJMG4>3.0.CO;2-P"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/mpo.2950170526"},{"key":"e_1_2_11_8_1","first-page":"102","article-title":"Malignant Neoplasms in Two Patients With Rubinstein\u2010Taybi Syndrome","volume":"13","author":"D'Cruz C.","year":"1993","journal-title":"Pediatric Pathology"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1014"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37800"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19990715)86:2<364::AID-CNCR21>3.0.CO;2-7"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.CD\u201021\u20100385"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2023.147233"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4630"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242115514"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2016.12.019"}],"container-title":["Congenital 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