Chromatin-Net explores phenotypic and molecular overlap of various rare syndromes associated with abnormal chromatin dynamics. These disorders include Coffin-Siris, Cornelia de Lange, Nicolaides-Baraitser & Borjeson-Forssman-Lehmann syndromes, which show an overlapping phenotypic presentation with a broad spectrum of dysmorphic features and variable degrees of cognitive impairment. To better characterise this overlap we will perform harmonised genotype-phenotype correlation including computerbased classification systems, we will analyse mosaic status and parent-of-origin effects in affected families (oder individuals) and identify and characterize new genes and phenotypes. To investigate possibly shared molecular processes and pathways, we will generate nucleosome positioning and DNA-methylation profiles, study transcriptomic changes as well as chromatin immunoprecipitation in various tissues and cell lines (e.g. induced pluripotent cells generated from patient fibroblasts and (neuronal) cells differentiated from induced pluripotent cells). Due to the use of shared materials and the highly complementary expertise of the different PIs we expect to gain new insights into genotypes, phenotypes, and molecular alterations of these clinically related disorders, which will improve genetic counselling of affected families and establish a basis for future therapeutic approaches.