biostudies-literatureDingemans AJMZonMw421https://www.ebi.ac.uk/biostudies/studies/S-EPMC9526704biostudies-literatureUnknown12(1)CHD8, a major autism gene, functions in chromatin remodelling and has various roles involving several biological pathways. Therefore, unsurprisingly, previous studies have shown that intellectual developmental disorder with autism and macrocephaly (IDDAM), the syndrome caused by pathogenic variants in CHD8, consists of a broad range of phenotypic abnormalities. We collected and reviewed 106 individuals with IDDAM, including 36 individuals not previously published, thus enabling thorough genotype-phenotype analyses, involving the CHD8 mutation spectrum, characterization of the CHD8 DNA methylation episignature, and the systematic analysis of phenotypes collected in Human Phenotype Ontology (HPO). We identified 29 unique nonsense, 25 frameshift, 24 missense, and 12 splice site variants. FurtTranslational psychiatryThe phenotypic spectrum and genotype-phenotype correlations in 106 patients with variants in major autism gene CHD8.PMC952670409150162010138Relator Rde Vries BBAPatterson WGMcConkey HMaas SMLee JAvan de Ven STruijen KMGKleefstra TGerkes EHBongers EMHFZou FVissers LELMStevenson REKievit AJAStumpel CTRMHeijligers MSadikovic BLohner KTedder MLLindy ABouman ADobson ATBernier RPrijoles EJDe Geus CMDingemans AJMvan Hagen JMde Graaff-Herder LEichler EEJansen PRKerkhof Jde Man SAStuurman KEZeidler SfalseThe phenotypic spectrum and genotype-phenotype correlations in 106 patients with variants in major autism gene CHD8.CHD8, a major autism gene, functions in chromatin remodelling and has various roles involving several biological pathways. Therefore, unsurprisingly, previous studies have shown that intellectual developmental disorder with autism and macrocephaly (IDDAM), the syndrome caused by pathogenic variants in CHD8, consists of a broad range of phenotypic abnormalities. We collected and reviewed 106 individuals with IDDAM, including 36 individuals not previously published, thus enabling thorough genotype-phenotype analyses, involving the CHD8 mutation spectrum, characterization of the CHD8 DNA methylation episignature, and the systematic analysis of phenotypes collected in Human Phenotype Ontology (HPO). We identified 29 unique nonsense, 25 frameshift, 24 missense, and 12 splice site variants. Furt2022-01-01T00:00:00Z2022 Oct2026-04-08T18:26:25.214Z2025-02-19T01:28:17.712ZS-EPMC95267043618295010.1038/s41398-022-02189-1