{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:44:05Z","timestamp":1792179845342,"version":"4.4.0"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,12,9]],"date-time":"2014-12-09T00:00:00Z","timestamp":1418083200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Assciazione RTS Una Vita Speciale"},{"name":"Assciazione Studio Malformazioni ONLUS"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:p>The genetic basis of Rubinstein\u2013Taybi syndrome (<jats:styled-content style=\"fixed-case\">RSTS<\/jats:styled-content>), a rare, sporadic, clinically heterogeneous disorder characterized by cognitive impairment and a wide spectrum of multiple congenital anomalies, is primarily due to private mutations in <jats:italic><jats:styled-content style=\"fixed-case\">CREBBP<\/jats:styled-content><\/jats:italic> (approximately 55% of cases) or <jats:italic><jats:styled-content style=\"fixed-case\">EP300<\/jats:styled-content><\/jats:italic> (approximately 8% of cases). Herein, we report the clinical and the genetic data taken from a cohort of 46 <jats:styled-content style=\"fixed-case\">RSTS<\/jats:styled-content> patients, all carriers of <jats:italic><jats:styled-content style=\"fixed-case\">CREBBP<\/jats:styled-content><\/jats:italic> point mutations. Molecular analysis revealed 45 different gene alterations including 31 inactivating (21 frameshift and 10 nonsense), 10 missense and 4 splicing mutations. Bioinformatic tools and transcript analyses were used to predict the functional effects of missense and splicing alterations. Of the 45 mutations, 42 are unreported and 3 were described previously. Recurrent mutations maybe a key tool in addressing genotype\u2013phenotype correlations in patients sharing the same defects (at the genomic or transcript level) and specific clinical signs, demonstrated here in two cases. The clinical data of our cohort evidenced frequent signs such as arched eyebrows, epicanthus, synophrys and\/or frontal hypertrichosis and broad phalanges that, previously overlooked in <jats:styled-content style=\"fixed-case\">RSTS<\/jats:styled-content> diagnosis, now could be considered. Some suggested correlations between organ\u2010specific anomalies and affected <jats:styled-content style=\"fixed-case\">CREB<\/jats:styled-content>\u2010binding protein domains broaden the <jats:styled-content style=\"fixed-case\">RSTS<\/jats:styled-content> clinical spectrum and perhaps will enhance patient follow\u2010up and clinical care.<\/jats:p>","DOI":"10.1111\/cge.12537","type":"journal-article","created":{"date-parts":[[2014,11,12]],"date-time":"2014-11-12T10:15:06Z","timestamp":1415787306000},"page":"431-440","source":"Crossref","is-referenced-by-count":62,"title":["Insights into genotype\u2013phenotype correlations from <i><scp>CREBBP<\/scp><\/i> point mutation screening in a cohort of 46 Rubinstein\u2013Taybi syndrome patients"],"prefix":"10.1111","volume":"88","author":[{"given":"S.","family":"Spena","sequence":"first","affiliation":[{"name":"Medical Genetics, Department of Health Sciences Universit\u00e0 degli Studi di Milano  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Milani","sequence":"additional","affiliation":[{"name":"Pediatric Highly Intensive Care Unit Fondazione IRCCS Ca' Granda, Ospedale Maggiore, Policlinico  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Rusconi","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Health Sciences Universit\u00e0 degli Studi di Milano  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Negri","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Health Sciences Universit\u00e0 degli Studi di Milano  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Colapietro","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Health Sciences Universit\u00e0 degli Studi di Milano  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Elcioglu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Marmara University School of Medicine  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Bedeschi","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Pilotta","sequence":"additional","affiliation":[{"name":"Centro di Auxoendocrinologia, Department of Paediatrics Spedali Civili  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Spaccini","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Children's Hospital V. Buzzi  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Ficcadenti","sequence":"additional","affiliation":[{"name":"Rare diseases Regional Centre, Pediatric Institute of Maternal\u2010Infantile Sciences Department Polytechnic University of Marche, Salesi Hospital of United Hospitals of Ancona  Ancona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Magnani","sequence":"additional","affiliation":[{"name":"Neonatology and Neonatal Intensive Care Unit, Maternal and Child Department Parma University  Parma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Scarano","sequence":"additional","affiliation":[{"name":"Medical Genetics Department Gaetano Rummo Hospital  Benevento Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Selicorni","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Universit\u00e0 Milano Bicocca, 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