{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T17:50:44Z","timestamp":1759773044354,"version":"3.41.2"},"reference-count":37,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Rubinstein\u2013Taybi syndrome (RSTS) is a rare congenital malformation syndrome with clinical characteristics such as hypertrichosis, high arched eyebrows, large beaked nose, and broad thumbs and halluces. RSTS patients showed intellectual disability and health problems such as short stature, ophthalmologic abnormalities, congenital heart defects, genitourinary defects, and variable types of tumors. Although mutations in <jats:italic>CREBBP<\/jats:italic> and <jats:italic>EP300<\/jats:italic> genes are associated with RSTS features, genetic causation is still unknown in 30% of patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We present clinical and molecular genetic characteristics of 25 unrelated Korean patients clinically diagnosed with RSTS. Sanger sequencing analysis and multiplex ligation\u2010dependent probe amplification for <jats:italic>CREBBP<\/jats:italic> in 25 patients and exome sequencing of <jats:italic>CREBBP<\/jats:italic>\u2010negative cases were performed in nine patients successively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Causative variants were identified in 20 (80%) patients: 16 (64%) in <jats:italic>CREBBP<\/jats:italic> and 4 (16%) in <jats:italic>EP300<\/jats:italic>. All the identified variants predict protein truncation (11 frameshift, 2 nonsense, 1 splicing\u2010site, and 6 large intragenic deletions); there are no repeatedly identified sequence variants. Four of the <jats:italic>CREBBP<\/jats:italic> and all four <jats:italic>EP300<\/jats:italic> variants are novel. Intellectual disability was noted in 24\/25 patients (96%); no difference was found between <jats:italic>CREBBP<\/jats:italic> and <jats:italic>EP300<\/jats:italic> groups. One patient with a <jats:italic>CREBBP<\/jats:italic> variant (4%) had malignant tumor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>To date, this is the largest cohort of patients with RSTS including <jats:italic>EP300<\/jats:italic>\u2010related patients in Korea. Future large\u2010scale studies to find genetic mutation of molecularly unsolved patients and long\u2010term prospective studies are required to validate our results.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1791","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T12:50:08Z","timestamp":1629809408000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Genetic and clinical heterogeneity in Korean patients with Rubinstein\u2013Taybi syndrome"],"prefix":"10.1002","volume":"9","author":[{"given":"Naye","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Pediatrics Seoul National University Hospital Seoul National University College of Medicine Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hwa Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Seoul National University Hospital Seoul National University College of Medicine Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byung Chan","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Seoul National University Hospital Seoul National University College of Medicine Seoul Korea"},{"name":"Rare Disease Center Seoul National University Hospital Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong\u2010Hee","family":"Chae","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Seoul National University Hospital Seoul National University College of Medicine Seoul Korea"},{"name":"Rare Disease Center Seoul National University Hospital Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soo Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Seoul National University Hospital Seoul National University College of Medicine Seoul Korea"},{"name":"Rare Disease Center Seoul National University Hospital Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0407-7828","authenticated-orcid":false,"given":"Jung Min","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Seoul National University Hospital Seoul National University College of Medicine Seoul Korea"},{"name":"Rare Disease Center Seoul National University Hospital Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,8,24]]},"reference":[{"issue":"4","key":"e_1_2_11_2_1","first-page":"406","article-title":"Rubinstein\u2010Taybi syndrome: New neuroradiological and neuropsychiatric insights from a multidisciplinary approach","volume":"177","author":"Ajmone P. F.","year":"2018","journal-title":"American Journal of Medical Genetics"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2018.05.019"},{"issue":"12","key":"e_1_2_11_4_1","first-page":"1244","article-title":"A case of rubinstein\u2010taybi syndrome","volume":"27","author":"Baik W. H.","year":"1984","journal-title":"Journal of Korean Pediatric Society"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33153"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-006-0215-0"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-005-1331-y"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36654"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.190629.115"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38603"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-020-01983-6"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61883"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/eye.2012.123"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddz174"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37940"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.5808\/GI.2012.10.4.214"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCD.0000000000000143"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201594"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/obr.12531"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-53889-1_3"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2014.07.007"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3341\/jkos.2011.52.6.766"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-018-0548-2"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-019-01985-y"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1037\/0735-7044.120.3.724"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.972"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399407000415"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-46601-1"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0035-1564571"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12537"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34058"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.3109\/13668250.2020.1776455"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61888"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.13124"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-0631"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-012-1254-4"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.10009"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms16035697"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1791","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.1791","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1791","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T12:38:23Z","timestamp":1693226303000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.1791"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,24]]},"references-count":37,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1002\/mgg3.1791"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.1791","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"type":"print","value":"2324-9269"},{"type":"electronic","value":"2324-9269"}],"subject":[],"published":{"date-parts":[[2021,8,24]]},"assertion":[{"value":"2021-03-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1791"}}