Figure 2.

Two-hit model of schizophrenia in 22q11.2DS. Mutations that are compensated for by an intact miRNA regulatory system can silently accumulate within individuals, with little selective pressure acting to remove them from the population. Deletion of 22q11.2 results in haploinsufficiency of DCGR8, a key gene involved in miRNA biogenesis. The resulting decrease in levels of certain miRNAs results in multiple regulatory mutations simultaneously exerting deleterious effects on the individual, resulting in schizophrenia or other serious abnormalities characteristic of 22q11.2DS.