Mental retardation and autism spectrum disorders tend to be concurrent. Because of the phenotypic overlap between these conditions, we sequenced SYNGAP1 in a series of 142 patients with sporadic autism spectrum disorders. Because SYNGAP1 interacts with NMDA receptor, which is thought to be involved in schizophrenia,20 we also sequenced SYNGAP1 in a series of 143 patients with schizophrenia. We observed no de novo, splicing, or truncating mutations in these series of subjects (Table 1). The number of de novo mutations in the SYNGAP1 coding sequence in the patients with nonsyndromic mental retardation was significantly higher than that in the rest of the tested series consisting of patients with autism spectrum disorders or schizophrenia and control subjects (P = 0.004 by Fisher’s exact test). In addition to the common I1115T variant, three unique heterozygous missense variants were found in subjects with autism spectrum disorders (P1238L) and schizophrenia (T1310M and T790N) (Table 1). These variants are not present in any SYNGAP1 functional domains, are unlikely to be pathogenic because they were transmitted from an unaffected parent, and are predicted to have no effect on protein function (according to several programs analyzing amino acid substitutions) (Table 2 in the Supplementary Appendix).
