{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Beard DC"],"funding":["NIMH","NICHD NIH HHS","Simons Foundation Autism Research Initiative","NIMH NIH HHS","NICHD","NINDS NIH HHS","NIAMS NIH HHS","NIGMS NIH HHS","NINDS"],"pagination":["113411"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10843706"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["42(11)"],"pubmed_abstract":["Phenotypic heterogeneity in monogenic neurodevelopmental disorders can arise from differential severity of variants underlying disease, but how distinct alleles drive variable disease presentation is not well understood. Here, we investigate missense mutations in DNA methyltransferase 3A (DNMT3A), a DNA methyltransferase associated with overgrowth, intellectual disability, and autism, to uncover molecular correlates of phenotypic heterogeneity. We generate a Dnmt3a<sup>P900L/+</sup> mouse mimicking a mutation with mild to moderate severity and compare phenotypic and epigenomic effects with a severe R878H mutation. P900L mutants exhibit core growth and behavioral phenotypes shared across models but show subtle epigenomic changes, while R878H mutants display extensive disruptions. We identif"],"journal":["Cell reports"],"pubmed_title":["Distinct disease mutations in DNMT3A result in a spectrum of behavioral, epigenetic, and transcriptional deficits."],"pmcid":["PMC10843706"],"funding_grant_id":["P50 HD103525","F31 HD100098","R01 MH117405","R01 NS041021","T32 GM007200","R01 AR075730"],"pubmed_authors":["Bell-Hensley A","Swift RG","Papouin T","Fuhler NA","Erickson A","Wu DY","McAlinden A","Gabel HW","Palmer CW","Hill CA","Hamagami N","Boua JV","Beard DC","McCullough KB","Zheng H","Noguchi KK","Maloney SE","Garbow JR","Zhang X","Martin JR","Ge X","Dougherty JD","Lawrence AB"],"additional_accession":[]},"is_claimable":false,"name":"Distinct disease mutations in DNMT3A result in a spectrum of behavioral, epigenetic, and transcriptional deficits.","description":"Phenotypic heterogeneity in monogenic neurodevelopmental disorders can arise from differential severity of variants underlying disease, but how distinct alleles drive variable disease presentation is not well understood. Here, we investigate missense mutations in DNA methyltransferase 3A (DNMT3A), a DNA methyltransferase associated with overgrowth, intellectual disability, and autism, to uncover molecular correlates of phenotypic heterogeneity. We generate a Dnmt3a<sup>P900L/+</sup> mouse mimicking a mutation with mild to moderate severity and compare phenotypic and epigenomic effects with a severe R878H mutation. P900L mutants exhibit core growth and behavioral phenotypes shared across models but show subtle epigenomic changes, while R878H mutants display extensive disruptions. We identif","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Nov","modification":"2026-05-29T17:48:34.423Z","creation":"2025-02-18T23:23:50.531Z"},"accession":"S-EPMC10843706","cross_references":{"pubmed":["37952155"],"doi":["10.1016/j.celrep.2023.113411"]}}