It is known that the genetic risk for schizophrenia is mostly accounted for by inherited alleles. However, recently, de novo mutations (large chromosomal copy number changes) have been shown to occur in a small fraction of cases and disproportionally disrupt genes encoding postsynaptic proteins.
Fromer et al. demonstrated that small de novo mutations, affecting one or a few nucleotides, are overrepresented among glutamatergic postsynaptic proteins comprising the ARC protein and NMDAR complexes. Similarly, proteins that interact with these complexes to modulate synaptic strength were particularly enriched (e.g. those whose mRNAs are targets of FMRP). The authors conclude that genes affected by mutations in schizophrenia overlap those mutated in autism and intellectual disability.
Nature. 2014 Feb 13;506(7487):179-84. De novo mutations in schizophrenia implicate synaptic networks. Fromer M, PMID: 24463507
Posted by Yannis Trakadis, MD