{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:23:49Z","timestamp":1792103029149,"version":"4.4.0"},"reference-count":24,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2016,6,17]],"date-time":"2016-06-17T00:00:00Z","timestamp":1466121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004726","name":"Ministry of Health","doi-asserted-by":"publisher","award":["RC2016"],"award-info":[{"award-number":["RC2016"]}],"id":[{"id":"10.13039\/501100004726","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":[[2016,10]]},"abstract":"<jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Mutations in\n                      <jats:italic>CREBBP<\/jats:italic>\n                      cause Rubinstein\u2013Taybi syndrome. By using exome sequencing, and by using Sanger in one patient,\n                      <jats:italic>CREBBP<\/jats:italic>\n                      mutations were detected in 11 patients who did not, or only in a very limited manner, resemble Rubinstein\u2013Taybi syndrome. The combined facial signs typical for Rubinstein\u2013Taybi syndrome were absent, none had broad thumbs, and three had only somewhat broad halluces. All had apparent developmental delay (being the reason for molecular analysis); five had short stature and seven had microcephaly. The facial characteristics were variable; main characteristics were short palpebral fissures, telecanthi, depressed nasal ridge, short nose, anteverted nares, short columella, and long philtrum. Six patients had autistic behavior, and two had self\u2010injurious behavior. Other symptoms were recurrent upper airway infections (n\u2009=\u20095), feeding problems (n\u2009=\u20097) and impaired hearing (n\u2009=\u20097). Major malformations occurred infrequently. All patients had a de novo missense mutation in the last part of exon 30 or beginning of exon 31 of\n                      <jats:italic>CREBBP<\/jats:italic>\n                      , between base pairs 5,128 and 5,614 (codons 1,710 and 1,872). No missense or truncating mutations in this region have been described to be associated with the classical Rubinstein\u2013Taybi syndrome phenotype. No functional studies have (yet) been performed, but we hypothesize that the mutations disturb protein\u2013protein interactions by altering zinc finger function. We conclude that patients with missense mutations in this specific\n                      <jats:italic>CREBBP<\/jats:italic>\n                      region show a phenotype that differs substantially from that in patients with Rubinstein\u2013Taybi syndrome, and may prove to constitute one (or more) separate entities. \u00a9 2016 Wiley Periodicals, Inc.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ajmg.a.37800","type":"journal-article","created":{"date-parts":[[2016,6,17]],"date-time":"2016-06-17T09:02:45Z","timestamp":1466154165000},"page":"2681-2693","source":"Crossref","is-referenced-by-count":68,"title":["<i>CREBBP<\/i>\n                    mutations in individuals without Rubinstein\u2013Taybi syndrome phenotype"],"prefix":"10.1002","volume":"170","author":[{"given":"Leonie A.","family":"Menke","sequence":"first","affiliation":[{"name":"Department of Pediatrics Academic Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine J.","family":"van Belzen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Leiden University Medical Center Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marielle","family":"Alders","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Academic Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Cristofoli","sequence":"additional","affiliation":[{"name":"Center for Human Genetics University Hospitals Leuven, KU Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The DDD Study","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja","family":"Ehmke","sequence":"additional","affiliation":[{"name":"Institute of Medical and Human Genetics Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Fergelot","sequence":"additional","affiliation":[{"name":"Department of Genetics, and INSERM U1211 University Hospital of Bordeaux Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Foster","sequence":"additional","affiliation":[{"name":"Institute of Cancer and Genomic Sciences University of Birmingham Birmingham United Kingdom"},{"name":"Clinical Genetics Unit University of Birmingham Birmingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica H.","family":"Gerkes","sequence":"additional","affiliation":[{"name":"Department of Genetics University Medical Center Groningen, University of Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari\u00ebtte J. V.","family":"Hoffer","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Leiden University Medical Center Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Horn","sequence":"additional","affiliation":[{"name":"Institute of Medical and Human Genetics Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarina G.","family":"Kant","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Leiden University Medical Center Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Lacombe","sequence":"additional","affiliation":[{"name":"Department of Genetics, and INSERM U1211 University Hospital of Bordeaux Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyby","family":"Leon","sequence":"additional","affiliation":[{"name":"Division of Genetics and Metabolism Children's National Health System Washington District of Columbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia M.","family":"Maas","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Academic Medical Center Amsterdam The Netherlands"},{"name":"Department of Clinical Genetics Academic Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Melis","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Science Federico II University Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Muto","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division Ospedale Pediatrico Bambino Ges\u00f9 Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo\u2010Mi","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Cambridge University Hospitals Cambridge United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilde","family":"Peeters","sequence":"additional","affiliation":[{"name":"Center for Human Genetics University Hospitals Leuven, KU Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorien J. 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