{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:52:19Z","timestamp":1792716739379,"version":"4.5.0"},"reference-count":21,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,2,20]],"date-time":"2018-02-20T00:00:00Z","timestamp":1519084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004257","name":"Helse Vest","doi-asserted-by":"publisher","award":["911810"],"award-info":[{"award-number":["911810"]}],"id":[{"id":"10.13039\/501100004257","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009647","name":"Ministry of Health","doi-asserted-by":"publisher","award":["RC2016"],"award-info":[{"award-number":["RC2016"]}],"id":[{"id":"10.13039\/100009647","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81400872"],"award-info":[{"award-number":["81400872"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81401193"],"award-info":[{"award-number":["81401193"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:sec><jats:label\/><jats:p>In 2016, we described that missense variants in parts of exons 30 and 31 of <jats:italic>CREBBP<\/jats:italic> can cause a phenotype that differs from Rubinstein\u2013Taybi syndrome (RSTS). Here we report on another 11 patients with variants in this region of <jats:italic>CREBBP<\/jats:italic> (between bp 5,128 and 5,614) and two with variants in the homologous region of <jats:italic>EP300<\/jats:italic>. None of the patients show characteristics typical for RSTS. The variants were detected by exome sequencing using a panel for intellectual disability in all but one individual, in whom Sanger sequencing was performed upon clinical recognition of the entity. The main characteristics of the patients are developmental delay (90%), autistic behavior (65%), short stature (42%), and microcephaly (43%). Medical problems include feeding problems (75%), vision (50%), and hearing (54%) impairments, recurrent upper airway infections (42%), and epilepsy (21%). Major malformations are less common except for cryptorchidism (46% of males), and cerebral anomalies (70%). Individuals with variants between bp 5,595 and 5,614 of <jats:italic>CREBBP<\/jats:italic> show a specific phenotype (ptosis, telecanthi, short and upslanted palpebral fissures, depressed nasal ridge, short nose, anteverted nares, short columella, and long philtrum). 3D face shape demonstrated resemblance to individuals with a duplication of 16p13.3 (the region that includes <jats:italic>CREBBP<\/jats:italic>), possibly indicating a gain of function. The other affected individuals show a less specific phenotype. We conclude that there is now more firm evidence that variants in these specific regions of <jats:italic>CREBBP<\/jats:italic> and <jats:italic>EP300<\/jats:italic> result in a phenotype that differs from RSTS, and that this phenotype may be heterogeneous.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38626","type":"journal-article","created":{"date-parts":[[2018,2,21]],"date-time":"2018-02-21T18:51:24Z","timestamp":1519239084000},"page":"862-876","source":"Crossref","is-referenced-by-count":80,"title":["Further delineation of an entity caused by <i>CREBBP<\/i> and <i>EP300<\/i> mutations but not resembling Rubinstein\u2013Taybi syndrome"],"prefix":"10.1002","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8312-7730","authenticated-orcid":false,"given":"Leonie A.","family":"Menke","sequence":"first","affiliation":[{"name":"Department of Pediatrics Academic Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The DDD study","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thatjana","family":"Gardeitchik","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hammond","sequence":"additional","affiliation":[{"name":"Big Data Institute and Nuffield Department of Obstetrics and Gynaecology University of Oxford Oxford United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ketil R.","family":"Heimdal","sequence":"additional","affiliation":[{"name":"Department of Medical genetics Oslo University Hospital Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Houge","sequence":"additional","affiliation":[{"name":"Center for medical genetics and molecular medicine Haukeland University Hospital Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia B.","family":"Hufnagel","sequence":"additional","affiliation":[{"name":"Division of Genetics and Metabolism Children's National Health System Washington District Of Columbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4941-3538","authenticated-orcid":false,"given":"Jianling","family":"Ji","sequence":"additional","affiliation":[{"name":"Division of Genomic Medicine Department of Pathology Children's Hospital Los Angeles and Keck USC School of Medicine Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Johansson","sequence":"additional","affiliation":[{"name":"Center for medical genetics and molecular medicine Haukeland University Hospital Bergen Norway"},{"name":"K.G. 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Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Ruivenkamp","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Leiden University Medical Center Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sulagna C.","family":"Saitta","sequence":"additional","affiliation":[{"name":"Division of Genomic Medicine Department of Pathology Children's Hospital Los Angeles and Keck USC School of Medicine Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology\/Genetics Xinhua Hospital Shanghai Jiao Tong University School of Medicine Shanghai Institute for Pediatric Research Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Tartaglia","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases 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