A new study from Mary-Claire King and colleagues reports exome sequencing in sporadic schizophrenia (Cell 154, 518–529, 2013). The goal of the study design was to enrich for de novo mutations by focusing on patients with sporadic (not familial) disease. The authors report exomes from 105 patients, 84 unaffected siblings and 210 unaffected parents. Forty-seven of the 105 probands (45%) carried de novo mutations predicted to damage protein function, whereas 25 of the 84 unaffected siblings (30%) harbored 35 such mutations. These results indicate a modest enrichment within probands of a higher likelihood of harboring at least one de novo damaging mutation (P = 0.035). The authors list the genes that carry damaging de novo mutations in patients, but none appear to be recurrently mutated. Further resequencing of these new candidates in large cohorts may be useful to prove causality. The authors performed transcriptional network analyses using RNA sequencing data from the BrainSpan Atlas and found that in fetal frontal cortex the networks of genes with de novo damaging mutations in patients showed greater connectedness in coexpression than networks derived from genes with de novo mutations in controls. This result offers support for the hypothesis that disruptions in fetal prefrontal cortical development are a key pathogenic mechanism in schizophrenia.