{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:54:54Z","timestamp":1793040894309,"version":"4.5.0"},"reference-count":26,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,10,11]],"date-time":"2020-10-11T00:00:00Z","timestamp":1602374400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Pathogenic variants in the homologous and highly conserved genes\u2014\n                    <jats:italic>CREBBP<\/jats:italic>\n                    and\n                    <jats:italic>EP300\u2014<\/jats:italic>\n                    are causal for Rubinstein\u2013Taybi syndrome (RSTS).\n                    <jats:italic>CREBBP<\/jats:italic>\n                    and\n                    <jats:italic>EP300<\/jats:italic>\n                    encode histone acetyltransferases (HAT) that act as transcriptional co\u2010activators, and their haploinsufficiency causes the pathology characteristic of RSTS by interfering with global transcriptional regulation. Though generally a well\u2010characterized syndrome, there is a clear phenotypic spectrum; rare associations have emerged with increasing diagnosis that is critical for comprehensive understanding of this rare syndrome. We present 12 unreported patients with RSTS found to have\n                    <jats:italic>EP300<\/jats:italic>\n                    variants discovered through gene sequencing and chromosomal microarray. Our cohort highlights rare phenotypic features associated with\n                    <jats:italic>EP300<\/jats:italic>\n                    variants, including imperforate anus, retained fetal finger pads, and spina bifida occulta. Our findings support the previously noted prevalence of pregnancy\u2010related hypertension\/preeclampsia seen with this disease. We additionally performed a meta\u2010analysis on our newly reported 12 patients and 62 of the 90 previously reported patients. We demonstrated no statistically significant correlation between phenotype severity (within the domains of intellectual disability and major organ involvement, as defined in our Methods section) and variant location and type; this is in contrast to the conclusions of some smaller studies and highlights the importance of large patient cohorts in characterization of this rare disease.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.61883","type":"journal-article","created":{"date-parts":[[2020,10,12]],"date-time":"2020-10-12T01:29:00Z","timestamp":1602466140000},"page":"2926-2938","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["<scp>\n                      <i>EP300<\/i>\n                    <\/scp>\n                    \u2010related\n                    <scp>Rubinstein\u2013Taybi<\/scp>\n                    syndrome: Highlighted rare phenotypic findings and a genotype\u2013phenotype meta\u2010analysis of 74 patients"],"prefix":"10.1002","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0385-1025","authenticated-orcid":false,"given":"Jennifer L.","family":"Cohen","sequence":"first","affiliation":[{"name":"Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia PA USA"},{"name":"Department of Pediatrics Perelman School of Medicine at the University of Pennsylvania  Philadelphia PA USA"},{"name":"Department of Pediatrics, Division of Medical Genetics Duke University School of Medicine  Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9194-0644","authenticated-orcid":false,"given":"Samantha A.","family":"Schrier Vergano","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Metabolism Children's Hospital of The King's Daughters  Norfolk VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Mazzola","sequence":"additional","affiliation":[{"name":"Genomic Medicine Institute Cleveland Clinic  Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alanna","family":"Strong","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia PA USA"},{"name":"Department of Pediatrics Perelman School of Medicine at the University of Pennsylvania  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth","family":"Keena","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carey","family":"McDougall","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4735-5223","authenticated-orcid":false,"given":"Alyssa","family":"Ritter","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3064-2488","authenticated-orcid":false,"given":"Emma C.","family":"Bedoukian","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah W.","family":"Burke","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Clinical Genetics University of Vermont Larner College of Medicine  Burlington VT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Paul C. Gaffney Division of Pediatric Hospital Medicine Children's Hospital of Pittsburgh  Pittsburgh PA USA"},{"name":"Department of Pediatrics, Divisions of General Academic Pediatrics and Pediatric Hospital Medicine Nemours Children's Health System  Orlando FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Zurcher","sequence":"additional","affiliation":[{"name":"Genomic Medicine Institute Cleveland Clinic  Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian D.","family":"Krantz","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia PA USA"},{"name":"Department of Pediatrics Perelman School of Medicine at the University of Pennsylvania  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7922-7480","authenticated-orcid":false,"given":"Kosuke","family":"Izumi","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia PA USA"},{"name":"Department of Pediatrics Perelman School of Medicine at the University of Pennsylvania  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5748-3507","authenticated-orcid":false,"given":"Elizabeth","family":"Bhoj","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia PA USA"},{"name":"Department of Pediatrics Perelman School of Medicine at the University of Pennsylvania  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine H.","family":"Zackai","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia PA USA"},{"name":"Department of Pediatrics Perelman School of Medicine at the University of Pennsylvania  Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Deardorff","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia PA USA"},{"name":"Department of Pediatrics Perelman School of Medicine at the University of Pennsylvania  Philadelphia PA USA"},{"name":"Department of Pathology Children's Hospital Los Angeles, Keck School of Medicine of the University of Southern California  Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2006.046698"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33153"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1752-1947-9-10"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37940"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32771"},{"issue":"3","key":"e_1_2_10_7_1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1097\/MCD.0000000000000262","article-title":"Rubinstein\u2010Taybi syndrome 2 with cerebellar abnormality and neural tube defect","volume":"28","author":"Hadzsiev K.","year":"2019","journal-title":"Clinical Dysmorphology"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCD.0000000000000143"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000448747"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13130"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-018-0548-2"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000375542"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38626"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22922"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12348"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1542\/pir.2016-0116"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399407000415"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1086\/429130"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpedi.1963.02080040590010"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ccr3.598"},{"issue":"5","key":"e_1_2_10_21_1","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1002\/ajmg.a.36883","article-title":"Expanding the phenotypic spectrum in EP300\u2010related Rubinstein\u2010Taybi syndrome","volume":"167","author":"Solomon B. D.","year":"2015","journal-title":"American Journal of Medical Genetics. Part A"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12098-015-1891-3"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2010.121"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.177"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36237"},{"issue":"5","key":"e_1_2_10_26_1","first-page":"1045","article-title":"Examination of the placenta","volume":"57","author":"Yetter J. F.","year":"1998","journal-title":"American Family Physician"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201791"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.61883","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.61883","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.61883","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T03:02:55Z","timestamp":1693796575000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.61883"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,11]]},"references-count":26,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["10.1002\/ajmg.a.61883"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.61883","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,11]]},"assertion":[{"value":"2020-04-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}