Functional Investigation of a GRIN2A Variant Associated with Rolandic Epilepsy

Identification of a GRIN2A missense mutation in a patient with Rolandic epilepsy. A GRIN2A sequencing schematic of the mutation c.1341T>A, p.N447K. B Interictal electroencephalogram obtained at nine years old showing frequent high-voltage spikes and spike-and-slow waves in the bilateral central-temporal regions, predominantly on the right. Red lines indicate abnormalities. C Topological model of a GluN1 and a GluN2A subunit. Residue N447 in GluN2A lies within the LBD. D Model of the glutamate- and glycine-bound LBDs of GluN1/GluN2A NMDARs (PDB ID: 5I57). The position of Asn447 is colored cyan and is indicated by the blue circle. The ligand glutamate in the GluN2 subunit and glycine in the GluN1 subunit are both colored green and are indicated by the red square and blue square, respectively. E Protein sequence alignment showing that residue N447 is highly conserved across higher vertebrates. An alternative substitution (N447A) was found in lower vertebrates