Objective: This study aims to analyze the electroclinical characteristics and gene test results of children on the severe end of the epilepsy aphasia spectrum (EAS) and also the correlation of EAS-related GRIN2A genes to explore the genotype-phenotype relationships, as well as potential pathogenic mechanism of EAS.Methods: A retrospective study was conducted on the participants diagnosed with Landau-Kleffner syndrome (LKS), epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS), and atypical benign partial epilepsy (ABPE) at the Children's Hospital of Chongqing Medical University from January 2013 to June 2019. Whole-exome sequencing was performed in six patients, and epileptic panel was carried out in two. In addition, we reviewed all the published literatures reporting EAS patients with pathogenic variants until June 2019 and conducted Gene Ontology (GO) analysis, as well as protein-protein interaction (PPI) network.Results: The mean age at seizure onset was 55.4 ± 27.0 months. The baseline severity of the spike-wave index (SWI) was not significantly correlated with intellectual disability (ID) level. Two pathogenic de novo GRIN2A null variants were identified in patients with ABPE who had less severe ID, despite the electrical status epilepticus during slow-wave sleep (ESES). By literature reviewing, 18 GRIN2A missense mutations and 11 GRIN2A truncating mutations which lead to N-methyl-d-aspartate receptors' loss of function has been reported. Of these mutations, 9 (31.0%) are situated in amino (N)-terminal domain, 6 (20.7%) in linger-binding domain S1, and 10 (34.5%) in linger-binding domain S2. EAS-related genes were enriched in the biological process of chemical synaptic transmission and vocalization (FDR,
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