biostudies-literatureHaghshenas SMinistero della SaluteJanivo FoundationChildren's Hospital FoundationGovernment of CanadaNIHR Manchester Biomedical Research CentreChildren’s Hospital FoundationGenome CanadaOntario Genomics Institute100287https://www.ebi.ac.uk/biostudies/studies/S-EPMC11040166biostudies-literatureUnknown5(3)CREB-binding protein (CBP, encoded by CREBBP) and its paralog E1A-associated protein (p300, encoded by EP300) are involved in histone acetylation and transcriptional regulation. Variants that produce a null allele or disrupt the catalytic domain of either protein cause Rubinstein-Taybi syndrome (RSTS), while pathogenic missense and in-frame indel variants in parts of exons 30 and 31 cause phenotypes recently described as Menke-Hennekam syndrome (MKHK). To distinguish MKHK subtypes and define their characteristics, molecular and extended clinical data on 82 individuals (54 unpublished) with variants affecting CBP (n = 71) or p300 (n = 11) (NP_004371.2 residues 1,705-1,875 and NP_001420.2 residues 1,668-1,833, respectively) were summarized. Additionally, genome-wide DNA methylation profiles HGG advancesMenke-Hennekam syndrome; delineation of domain-specific subtypes with distinct clinical and DNA methylation profiles.PMC110401662018241WAR2018-05OGI-18802C502_2005NIHR203308Clayton-Smith JPatterson JLin RKant SGMerla GHufnagel SBCueto Gonzalez AMSluga ARusso RSSantos-Simarro FO'Brien AGarcia-Minaur SVerbeek NHurst ACEGaravelli LSchultz-Rogers LKois CSaitta SCWhite SMSadikovic Bvan den Elzen APMPes VBedoukian ELlano-Rivas IHorn DPrijoles EJLynch SAFergelot PKlee EWLeon ELacombe DPotocki LPersani LMKHK Research ConsortiumFisher LCrisponi LBhai PThe Ddd StudyKaiser FJGarrido EDMelis DMcConkey HFaivre LShashi VGerkes EHMenke LASchijns JMJenkins ZABanka SSanten GWETartaglia MDevriendt KHaghshenas SMerati EGardeitchik TLauffer PSotgiu SNewbury-Ecob RSuri MLevy MASimpson BNIlencikova DAngius AHouge GJulia SXiao BSchaefer EBhambhani VMaas SMTerhal PRake JPAlders MKinning EParenti IGalazzi ERutz ARobertson SPGiltay JCde Waard VRea GEhmke NMaitz SBFoster ASun YPrasad CTully IFriedman JWenzel MBaker JAKerkhof JBout HJRagge NKvan Eerde APark SMWilliams EMLebrun MKovacevic Mvan Ravenswaaij-Arts CMAPeeters HGarcia AGMartinez-Monseny AFMcKee SLanpher BSteichen-Gersdorf EHalliday BJPersico ISullivan JAPotjer Tvan Gils JWitteveen LTedder MLichty AWRuivenkamp CPollazzon MHuisman SAPottinger CMonteiro FPBrady AFHeimdal KRPetit FGabau EBodamer ONizon MFlores-Daboub JALachmeijer AMAGfalseMenke-Hennekam syndrome; delineation of domain-specific subtypes with distinct clinical and DNA methylation profiles.CREB-binding protein (CBP, encoded by CREBBP) and its paralog E1A-associated protein (p300, encoded by EP300) are involved in histone acetylation and transcriptional regulation. Variants that produce a null allele or disrupt the catalytic domain of either protein cause Rubinstein-Taybi syndrome (RSTS), while pathogenic missense and in-frame indel variants in parts of exons 30 and 31 cause phenotypes recently described as Menke-Hennekam syndrome (MKHK). To distinguish MKHK subtypes and define their characteristics, molecular and extended clinical data on 82 individuals (54 unpublished) with variants affecting CBP (n = 71) or p300 (n = 11) (NP_004371.2 residues 1,705-1,875 and NP_001420.2 residues 1,668-1,833, respectively) were summarized. Additionally, genome-wide DNA methylation profiles 2024-01-01T00:00:00Z2024 Jul2026-06-02T01:43:04.512Z2026-04-13T03:12:20.882ZS-EPMC110401663855385110.1016/j.xhgg.2024.100287