{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:11:07Z","timestamp":1790244667880,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":266,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    KAT6B\u2010related disorders (KRDs) comprise a\n                    <jats:italic>spectrum<\/jats:italic>\n                    of developmental disorders ranging from Genitopatellar syndrome (GPS) to Say\u2013Barber\u2013Biesecker\u2013Young\u2013Simpson syndrome (SBBYSS), with increasing recognition of intermediate phenotypes. Although genotype\u2013phenotype correlations have progressively emerged, the molecular basis of phenotypic variability remains incompletely understood. We performed comprehensive clinical phenotyping and trio\u2010based whole\u2010exome sequencing (WES) in two unrelated individuals carrying novel de novo\n                    <jats:italic>KAT6B<\/jats:italic>\n                    variants. Transcriptomic analysis was undertaken for the noncanonical intronic variant using peripheral blood\u2010derived RNA. An updated review of molecularly confirmed KRDs was also performed to reassess genotype\u2013phenotype correlations and protein domain\u2010specific variant distribution. Patient 1 carried a novel nonsense variant (c.5347G&gt;T, p.Glu1783Ter) and presented with a predominantly SBBYSS\u2010like phenotype. Patient 2 harbored a novel noncanonical intronic variant (c.3665\u201021C&gt;A) associated with a severe multisystem phenotype overlapping the GPS\n                    <jats:italic>spectrum<\/jats:italic>\n                    . RNA sequencing demonstrated preserved canonical exon 17\u201318 splicing but an approximately 50% reduction in\n                    <jats:italic>KAT6B<\/jats:italic>\n                    transcript abundance, supporting a dosage\u2010sensitive pathogenic mechanism. Review of 203 published individuals identified 133 distinct pathogenic variants, confirmed exon 18 as the major mutational hotspot, and suggested domain\u2010specific genotype\u2013phenotype trends, including enrichment of SBBYSS\u2010associated phenotypes among variants affecting the histone acetyltransferase (HAT) domain. Both patients also exhibited severe upper airway dysfunction with obstructive sleep apnea (OSA). These findings expand the molecular and phenotypic\n                    <jats:italic>spectrum<\/jats:italic>\n                    of KRDs, provide supportive transcriptomic evidence for a potential functional intronic variant, refine current genotype\u2013phenotype correlations, and highlight upper airway dysfunction as a clinically relevant but likely underrecognized manifestation across the KRD\n                    <jats:italic>spectrum<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1155\/humu\/6378376","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:50:07Z","timestamp":1790243407000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical and Molecular Delineation of\n                    <i>KAT6B<\/i>\n                    \u2010Related Disorders: Novel Variants and Refined Genotype\u2013Phenotype Correlations"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9660-7397","authenticated-orcid":false,"given":"Vito Luigi","family":"Colona","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0764-686X","authenticated-orcid":false,"given":"Maria","family":"Gnazzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalidia","family":"Donato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lavinia","family":"Fioretti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9748-3982","authenticated-orcid":false,"given":"Alessandra","family":"Terracciano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0014-7574","authenticated-orcid":false,"given":"Delia","family":"Monopoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7944-8400","authenticated-orcid":false,"given":"Paola Sabrina","family":"Buonuomo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1753-5963","authenticated-orcid":false,"given":"Michaela Veronika","family":"Gonfiantini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Lettori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7239-6337","authenticated-orcid":false,"given":"Roberta","family":"Taurisano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0434-8533","authenticated-orcid":false,"given":"Tommaso","family":"Mazza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1223-7358","authenticated-orcid":false,"given":"Daniela","family":"Concolino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2228-8271","authenticated-orcid":false,"given":"Mafalda","family":"Mucciolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7409-8299","authenticated-orcid":false,"given":"Marina","family":"Macchiaiolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9037-4297","authenticated-orcid":false,"given":"Antonio","family":"Novelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2907-3206","authenticated-orcid":false,"given":"Davide","family":"Vecchio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"e_1_2_15_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.200900051"},{"key":"e_1_2_15_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.10.008"},{"key":"e_1_2_15_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.11.023"},{"key":"e_1_2_15_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22141"},{"key":"e_1_2_15_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI43428"},{"key":"e_1_2_15_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-0811-8"},{"key":"e_1_2_15_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI167672"},{"key":"e_1_2_15_8_2","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202402969"},{"key":"e_1_2_15_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.23.3.242"},{"key":"e_1_2_15_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2015.09.004"},{"key":"e_1_2_15_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.64100"},{"key":"e_1_2_15_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_15_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23798"},{"key":"e_1_2_15_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2019.02.012"},{"key":"e_1_2_15_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2020.100729"},{"key":"e_1_2_15_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1809"},{"key":"e_1_2_15_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-023-02560-2"},{"key":"e_1_2_15_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13353-023-00824-1"},{"key":"e_1_2_15_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-020-02053-9"},{"key":"e_1_2_15_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbad284"},{"key":"e_1_2_15_21_2","doi-asserted-by":"publisher","DOI":"10.1080\/21691401.2026.2612914"}],"container-title":["Human 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