本期Nature 发表了对精神分裂症患者及其亲属所做的两项重要外显子组（基因组的蛋白编码部分）测序研究。这两项研究一起为了解在精神分裂症中破坏谷氨酸能突触的特定致病机制提供了可靠线索。影响支架蛋白ARC（“活性调控的与细胞骨架相关的蛋白”）功能的突变在其中的参与尤为明显，“脆弱X智力迟钝蛋白” (FMRP)的目标中所发生的突变也是这样。FMRP的缺陷以前曾被发现与“泛自闭症”有关。
Inherited alleles account for most of the genetic risk for schizophrenia. However, new (de novo) mutations, in the form of large chromosomal copy number changes, occur in a small fraction of cases and disproportionally disrupt genes encoding postsynaptic proteins. Here we show that small de novo mutations, affecting one or a few nucleotides, are overrepresented among glutamatergic postsynaptic proteins comprising activity-regulated cytoskeleton-associated protein (ARC) and N-methyl-D-aspartate receptor (NMDAR) complexes. Mutations are additionally enriched in proteins that interact with these complexes to modulate synaptic strength, namely proteins regulating actin filament dynamics and those whose messenger RNAs are targets of fragile X mental retardation protein (FMRP). Genes affected by mutations in schizophrenia overlap those mutated in autism and intellectual disability, as do mutation-enriched synaptic pathways. Aligning our findings with a parallel case–control study, we demonstrate reproducible insights into aetiological mechanisms for schizophrenia and reveal pathophysiology shared with other neurodevelopmental disorders.