Moreover, our results showed gene dosage effects caused either directly by genes located on HSA21 (e.g. SOD1, APP, DONSON, TIAM1, COL6A2, ITSN1 and BACE2) or indirectly by HSA21 interactors, highlighting the intrinsic complexity of the DS pathology. Here, COL6A2 is linked to Dravet syndrome.