{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:23:50Z","timestamp":1792103030138,"version":"4.4.0"},"reference-count":39,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2016,9,20]],"date-time":"2016-09-20T00:00:00Z","timestamp":1474329600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:sec><jats:label\/><jats:p>Rubinstein\u2013Taybi syndrome (RSTS) is a developmental disorder characterized by a typical face and distal limbs abnormalities, intellectual disability, and a vast number of other features. Two genes are known to cause RSTS, <jats:italic>CREBBP<\/jats:italic> in 60% and <jats:italic>EP300<\/jats:italic> in 8\u201310% of clinically diagnosed cases. Both paralogs act in chromatin remodeling and encode for transcriptional co\u2010activators interacting with &gt;400 proteins. Up to now 26 individuals with an <jats:italic>EP300<\/jats:italic> mutation have been published. Here, we describe the phenotype and genotype of 42 unpublished RSTS patients carrying <jats:italic>EP300<\/jats:italic> mutations and intragenic deletions and offer an update on another 10 patients. We compare the data to 308 individuals with <jats:italic>CREBBP<\/jats:italic> mutations. We demonstrate that <jats:italic>EP300<\/jats:italic> mutations cause a phenotype that typically resembles the classical RSTS phenotype due to <jats:italic>CREBBP<\/jats:italic> mutations to a great extent, although most facial signs are less marked with the exception of a low\u2010hanging columella. The limb anomalies are more similar to those in <jats:italic>CREBBP<\/jats:italic> mutated individuals except for angulation of thumbs and halluces which is very uncommon in <jats:italic>EP300<\/jats:italic> mutated individuals. The intellectual disability is variable but typically less marked whereas the microcephaly is more common. All types of mutations occur but truncating mutations and small rearrangements are most common (86%). Missense mutations in the HAT domain are associated with a classical RSTS phenotype but otherwise no genotype\u2013phenotype correlation is detected. Pre\u2010eclampsia occurs in 12\/52 mothers of <jats:italic>EP300<\/jats:italic> mutated individuals versus in 2\/59 mothers of CREBBP mutated individuals, making pregnancy with an <jats:italic>EP300<\/jats:italic> mutated fetus the strongest known predictor for pre\u2010eclampsia. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37940","type":"journal-article","created":{"date-parts":[[2016,9,20]],"date-time":"2016-09-20T13:53:00Z","timestamp":1474379580000},"page":"3069-3082","source":"Crossref","is-referenced-by-count":121,"title":["Phenotype and genotype in 52 patients with Rubinstein\u2013Taybi syndrome caused by <i>EP300<\/i> mutations"],"prefix":"10.1002","volume":"170","author":[{"given":"Patricia","family":"Fergelot","sequence":"first","affiliation":[{"name":"Department of Genetics, and INSERM U1211 University Hospital of Bordeaux Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Van Belzen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Leiden University Medical Center Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Van Gils","sequence":"additional","affiliation":[{"name":"Department of Genetics University Hospital Center Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Afenjar","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de G\u00e9n\u00e9tique Hospital Armand Trousseau\u2010La Roche\u2010Guyon AP\u2010HP Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M.","family":"Armour","sequence":"additional","affiliation":[{"name":"Regional Genetics Unit  Children's Hospital of Eastern Ontario Ottawa Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Arveiler","sequence":"additional","affiliation":[{"name":"Department of Genetics, and INSERM U1211 University Hospital of Bordeaux Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lex","family":"Beets","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Academic Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydie","family":"Burglen","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de G\u00e9n\u00e9tique Hospital Armand Trousseau\u2010La Roche\u2010Guyon AP\u2010HP Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Busa","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de G\u00e9n\u00e9tique Clinique Hospital La Timone AP\u2010HM Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Collet","sequence":"additional","affiliation":[{"name":"D\u00e9partement de G\u00e9n\u00e9tique Hospital Necker\u2010Enfants Malades AP\u2010HP Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Deforges","sequence":"additional","affiliation":[{"name":"Department of Genetics University Hospital Center Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert B. 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