Neonates with the KCNQ2 Y755C Variants: Not Associated with Neonatal Epileptic Encephalopathy

Abstract

Background: Pediatric epilepsy caused by a KCNQ2 gene mutation usually manifests the phenotype of a neonatal seizure. KCNQ2 encephalopathy in newborns continues to be reported on. Objectives: The exact mechanism and phenotype of the KCNQ2 mutation still require investigation. Methods: One hundred twenty-one patients with childhood epilepsy without an identified cause underwent KCNQ2 sequencing. KCNQ2 mutation variants were transfected into human embryonic kidney 293 (HEK293) cells to investigate functional changes. Results: Two patients with the c.2264G>G/A (p.Y755C) variant had neonatal epileptic encephalopathy: one had electroencephalography (EEG) burst suppression and the other had multiple focal spikes. However, the mutation was not found in the 80 healthy adult claiming without ever seizures before. A functional study showed that p.Y755C currents were not different from those in the wild-type and from those in the benign (p.N780T) polymorphism in homomeric and heteromeric (wild-type KCNQ2: mutant = 1:1) transfected HEK293 cells. Electrical current differences between HEK293 cells with wildtype mutations and cells transfected with the wild-type KCNQ2, KCNQ3, and p.Y755C mutations in a 1:2:1 ratio were not significant. Their seizures remitted after they turned 1 year old. Conclusion: We suggest that patients with the KCNQ2 p.Y755C mutations are not associated with neonatal epileptic encephalopathy