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Menke-Hennekam syndrome; delineation of domain-specific subtypes with distinct clinical and DNA methylation profiles.

dc.rights.licenseopenen_US
dc.contributor.authorHAGHSHENAS, Sadegheh
dc.contributor.authorBOUT, Hidde J
dc.contributor.authorSCHIJNS, Josephine M
dc.contributor.authorLEVY, Michael A
dc.contributor.authorKERKHOF, Jennifer
dc.contributor.authorBHAI, Pratibha
dc.contributor.authorMCCONKEY, Haley
dc.contributor.authorJENKINS, Zandra A
dc.contributor.authorWILLIAMS, Ella M
dc.contributor.authorHALLIDAY, Benjamin J
dc.contributor.authorHUISMAN, Sylvia A
dc.contributor.authorLAUFFER, Peter
dc.contributor.authorDE WAARD, Vivian
dc.contributor.authorWITTEVEEN, Laura
dc.contributor.authorBANKA, Siddharth
dc.contributor.authorBRADY, Angela F
dc.contributor.authorGALAZZI, Elena
hal.structure.identifierService de génétique médicale
hal.structure.identifierUniversité de Bordeaux [UB]
hal.structure.identifierCHU de Bordeaux Pellegrin [Bordeaux]
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorVAN GILS, Julien
dc.contributor.authorHURST, Anna C E
dc.contributor.authorKAISER, Frank J
hal.structure.identifierHôpital Pellegrin
hal.structure.identifierService de génétique médicale
hal.structure.identifierUniversité de Bordeaux [UB]
hal.structure.identifierCentre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorLACOMBE, Didier
dc.contributor.authorMARTINEZ-MONSENY, Antonio F
hal.structure.identifierHôpital Pellegrin
hal.structure.identifierService de génétique médicale
hal.structure.identifierCentre Génomique Fonctionnelle Bordeaux [Bordeaux] [CGFB]
hal.structure.identifierUniversité de Bordeaux [UB]
hal.structure.identifierCentre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorFERGELOT, Patricia
dc.contributor.authorMONTEIRO, Fabíola P
dc.contributor.authorPARENTI, Ilaria
dc.contributor.authorPERSANI, Luca
dc.contributor.authorSANTOS-SIMARRO, Fernando
dc.contributor.authorSIMPSON, Brittany N
dc.contributor.authorALDERS, Mariëlle
dc.contributor.authorROBERTSON, Stephen P
dc.contributor.authorSADIKOVIC, Bekim
dc.contributor.authorMENKE, Leonie A
dc.date.accessioned2024-07-16T08:26:53Z
dc.date.available2024-07-16T08:26:53Z
dc.date.issued2024-03-29
dc.identifier.issn2666-2477en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/200956
dc.description.abstractEnCREB-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 were assessed in DNA extracted from whole peripheral blood from 54 individuals. Most variants clustered closely around the zinc-binding residues of two zinc-finger domains (ZZ and TAZ2) and within the first α helix of the fourth intrinsically disordered linker (ID4) of CBP/p300. Domain-specific methylation profiles were discerned for the ZZ domain in CBP/p300 (found in nine out of 10 tested individuals) and TAZ2 domain in CBP (in 14 out of 20), while a domain-specific diagnostic episignature was refined for the ID4 domain in CBP/p300 (in 21 out of 21). Phenotypes including intellectual disability of varying degree and distinct physical features were defined for each of the regions. These findings demonstrate existence of at least three MKHK subtypes, which are domain specific (MKHK-ZZ, MKHK-TAZ2, and MKHK-ID4) rather than gene specific (CREBBP/EP300). DNA methylation episignatures enable stratification of molecular pathophysiologic entities within a gene or across a family of paralogous genes.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subject.enCREB-binding protein
dc.subject.enDNA methylation
dc.subject.enE1A-associated protein p300
dc.subject.enMKHK
dc.subject.enMenke-Hennekam syndrome
dc.subject.enRubinstein-Taybi syndrome
dc.subject.enEpisignatures
dc.subject.enIntellectual disability
dc.subject.enIntrinsically disordered linker
dc.subject.enZinc-finger domain
dc.title.enMenke-Hennekam syndrome; delineation of domain-specific subtypes with distinct clinical and DNA methylation profiles.
dc.title.alternativeHGG Adven_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/j.xhgg.2024.100287en_US
dc.subject.halSciences du Vivant [q-bio]/Génétiqueen_US
dc.identifier.pubmed38553851en_US
bordeaux.journalHuman Genetics and Genomics Advancesen_US
bordeaux.page100287en_US
bordeaux.volume5en_US
bordeaux.hal.laboratoriesMaladies Rares : Génétique et Métabolisme (MRGM) - UMR 1211en_US
bordeaux.issue3en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDGenome Canadaen_US
bordeaux.identifier.funderIDOntario Genomics Instituteen_US
bordeaux.identifier.funderIDManchester Biomedical Research Centreen_US
bordeaux.identifier.funderIDEuropean Rare Kidney Disease Reference Networken_US
bordeaux.import.sourcepubmed
hal.identifierhal-04649255
hal.version1
hal.date.transferred2024-07-16T08:26:59Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
workflow.import.sourcepubmed
dc.rights.ccCC BYen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Human%20Genetics%20and%20Genomics%20Advances&rft.date=2024-03-29&rft.volume=5&rft.issue=3&rft.spage=100287&rft.epage=100287&rft.eissn=2666-2477&rft.issn=2666-2477&rft.au=HAGHSHENAS,%20Sadegheh&BOUT,%20Hidde%20J&SCHIJNS,%20Josephine%20M&LEVY,%20Michael%20A&KERKHOF,%20Jennifer&rft.genre=article


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