Multiple de novo mutations (GluN1-D552E, GluN1-P557R, GluN2A-A548T, GluN2A-P552R, GluN2B-P553L) (Fig 2B–2D) (Table 2) have been identified in the pre-M1 region in patients with epilepsy and/or developmental delay [20–23], however there is no information available about the effects of these missense mutations on NMDAR function. This evidence concerns the gene GRIN2A and Global developmental delay.