Genotype-phenotype-epiphenotype analysis to decipher severity, penetrance, pleiotropy and mechanisms in CHD8-related neurodevelopmental disorder

Peripheral blood DNA methylation (DNAm)-based episignature analysis has emerged as an important diagnostic tool. We analysed the relationship between variant type/severity, clinical phenotypes, and epiphenotypes in a cohort of individuals with rare CHD8 variants. Furthermore, we performed DNAm studies in Chd8+/- mouse neocortex to comparatively assess the effect of CHD8 loss-of-function on DNA methylome in a cross-species, cross-tissue manner. Overall design: To investigate DNA methylome changes in CHD8-IDDAM mouse neocortical models.