{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T04:41:45Z","timestamp":1760589705160,"version":"build-2065373602"},"reference-count":33,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Rubinstein\u2013Taybi syndrome (RSTS) is characterized by intellectual disability, short stature, distinctive facial dysmorphism, broad thumbs\/halluces, hearing loss, congenital heart or renal defects, and cryptorchidism in males. Pathogenic variants in CREBBP (~90% of cases) or EP300 (~10%) underlie the disorder, with ~88% single nucleotide variants (SNVs) and ~12% copy number variants (CNVs) in CREBBP. Materials and Methods: We investigated 17 patients clinically diagnosed with RSTS at a tertiary hospital in Poland. Genetic confirmation was achieved by next-generation sequencing, multiplex ligation-dependent probe amplification (MLPA), array comparative genomic hybridization (aCGH), or Sanger sequencing. Results: Pathogenic variants were identified in CREBBP (13\/17, 76%) and EP300 (4\/17, 24%). Variant types included frameshift indels (6\/17, 35%), missense (4\/17, 24%), nonsense (3\/17, 18%), splice-site (2\/17, 12%), and gross deletions (2\/17, 12%). Notably, 13\/17 (76%) were novel: ten in CREBBP (c.\u221249_12del, c.289C&gt;T, c.1093_1096del, c.1094A&gt;G, c.3178A&gt;T, c.3401A&gt;T, c.(3836+1_3837\u22121)_(4394+1_4395\u22121)del, c.4133+2T&gt;G, c.4963dup, c.5028_5029dup) and three in EP300 (c.1942C&gt;T, c.3044_3045del, c.4713_4722del). Among the novel CREBBP variants, eight occurred de novo and two had unknown inheritance. Two novel EP300 variants occurred de novo and one was of unknown origin. Conclusions: This first Polish RSTS cohort demonstrates a considerable proportion of gross deletions (12% overall; 15% in CREBBP) and an unexpectedly high rate of novel variants (76%), suggesting possible population-specific differences. These findings underscore the genetic heterogeneity of RSTS and highlight the importance of comprehensive molecular diagnostics and studies in underrepresented populations.<\/jats:p>","DOI":"10.3390\/genes16101206","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T10:37:14Z","timestamp":1760438234000},"page":"1206","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rubinstein\u2013Taybi Syndrome: A Comprehensive Analysis of a Polish Cohort with Most Cases Due to Novel CREBBP and EP300 Variants"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0603-7763","authenticated-orcid":false,"given":"Agata","family":"Cie\u015blikowska","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, The Children\u2019s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7671-2848","authenticated-orcid":false,"given":"Agnieszka","family":"Madej-Pilarczyk","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, The Children\u2019s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piotr","family":"Iwanowski","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, The Children\u2019s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Iwanicka-Pronicka","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, The Children\u2019s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8360-0006","authenticated-orcid":false,"given":"Dorota","family":"Wicher","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, The Children\u2019s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"J\u0119drzejowska","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, The Children\u2019s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland"},{"name":"Department of Medical Genetics, Institute of Mother and Child, ul. Kasprzaka 17a, 01-211 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorota","family":"Jurkiewicz","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, The Children\u2019s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marzena","family":"Gawlik","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, The Children\u2019s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorota","family":"Piekutowska-Abramczuk","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, The Children\u2019s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1064-0277","authenticated-orcid":false,"given":"Paulina","family":"Halat-Wolska","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, The Children\u2019s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jagoda","family":"B\u0142aszkiewicz","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, The Children\u2019s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Izabela","family":"Mendrek","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, The Children\u2019s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3888-0624","authenticated-orcid":false,"given":"Krystyna","family":"Chrzanowska","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, The Children\u2019s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8685-5795","authenticated-orcid":false,"given":"Marlena","family":"M\u0142ynek","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, The Children\u2019s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piotr","family":"Stawi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Medical University of Warsaw, ul. \u017bwirki i Wigury 61, 02-091 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna","family":"Kosi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Medical University of Warsaw, ul. \u017bwirki i Wigury 61, 02-091 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8721-210X","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Krajewska-Walasek","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, The Children\u2019s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1065-7968","authenticated-orcid":false,"given":"El\u017cbieta","family":"Ciara","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, The Children\u2019s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1001\/archpedi.1963.02080040590010","article-title":"Broad Thumbs and Toes and Facial Abnormalities. A Possible Mental Retardation Syndrome","volume":"105","author":"Rubinstein","year":"1963","journal-title":"Am. J. Dis. Child."},{"key":"ref_2","first-page":"17","article-title":"Rubinstein-Taybi Syndrome in The Netherlands","volume":"6","author":"Hennekam","year":"1990","journal-title":"Am. J. Med. 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