SZ is a very complex disorder caused by multivariate genetic and environmental factors. Apart from familial factors, such as being the monozygotic co-twin of a SZ proband or being the offspring of two parents with the condition, 22q11.2 deletion is the highest known risk factor for the development of SZ [1]. 22q11.2 Deletion Syndrome (22q11.2DS) has a highly variable clinical presentation including velo-cardio-facial syndrome (VCFS), cognitive and behavioral disorders, and SZ-like psychosis [2–7]. Several genes in the deleted region have been suggested as candidates for the development of SZ, including TBX1 [8], COMT [9–11], GNB1L [12], PRODH [13–16], and DGCR8 [17–19]. It is, however, thought that the 22q11.2 DS reflects combinatorial effects of diminished dosage of multiple genes/miRNAs acting on common cellular processes involved in neuronal development and neurotransmission [20, 21]. From this perspective, it is speculated that downstream targets affected by deleted genes may be enriched in cellular pathways involved in neuronal development or neuronal activity, and that reduced expression of the deleted genes may dysregulate these pathways.
