The DLG (discs large) family of membrane-associated guanylate kinases (MAGUKs), which were hit by multiple case de novo CNVs, are components of postsynaptic signalling complexes that are embedded within the larger group of over 1000 proteins that make up the PSD.34 They are associated with NMDA receptors and are highly concentrated in synapses. Remarkably, the orthologue of DLG2 in Drosophila (dlg1) is directly regulated by the orthologue of EHMT1 (emht also known as G9a).33 CNVs spanning DLG1 and DLG2 have been reported before in schizophrenia4, 6, 17 whereas other members of the family (DLG3 and DLGAP2) have been implicated in mental retardation35 and autism.30, 36 Together with our observation of multiple de novos spanning members of this family, and the nominally significant association of exonic CNVs at DLG2 in the case– control analysis, the findings strongly suggest that the CNVs we report in DLG-related genes are likely to be of pathogenic relevance to schizophrenia.
