Abstracts

Rationale: Non-lesional epilepsy in children is usually genetically heterogeneous. The common genetic cause includes a KCNQ2 gene mutation, which usually manifests the phenotype of a neonatal seizure during the first week of life; however, febrile seizures, benign childhood epilepsy with centrotemporal spikes, childhood absence seizures, and idiopathic photosensitive convulsions have also been reported. The mutant gene is located at 20q13, a voltage-gated potassium-channel gene. KCNQ2 encephalopathy with mental retardation and refractory seizures continues to be reported, which highlights that KCNQ2 is important in children with epilepsy, whereas, the exact mechanism and phenotype of the KCNQ2 mutation and childhood epilepsy are still unknown. Methods: We studied the KCNQ2 genotype from 75 non-relative patients (age range: 2 days to 18 years old), whom have non-lesional epilepsy. The study also screens KCNQ2 from 50 healthy controls without epilepsy. We use next generation sequences in 55 patients, and direct sequence in 20 patients to screen KCNQ2 mutation variants. Results: Eight (8/75, 11%) cases were identified KCNQ2 mutations, including c. 1545 G>G/C (p.E515D) in 4 patients; c.1627G>A (p.V543M) in one; c.1294 C > T (p.R431C) in one; and c. 2264 G>G/A (p.Y755C) in 2; however, none of these mutation variants were found in the control group. All 4 mutations are predicated to be deleterious by the computerbased algorithms SIFT and PolyPhen. Mutations, c.1627G>A (p.V543M) and c.1294 C > T (p.R431C), are novel mutations. All patients with p.E515D cause epilepsy, however, their controlling seizures were favorable, and with 3 normal intelligence and one mild intelligent disability. Two patients carrying p.Y755C cause neonatal seizures with suppression-bursting EEG in one, and multiple focal spikes in another case. We did the functional test by HEK 293 cell in c. 1545 G>G/C (p.E515D) and c.1627G>A (p.V543M), which showed p.V543M have more favorable electrophysiology than p.E515D. Conclusions: Based on these findings, we conclude that KCNQ2 mutation variants probable are not limited the cause of neonatal seizures. The KCNQ2 mutation account for about 10% of idiopathic epilepsy in children, it should be a candidate gene when diagnosing idiopathic childhood epilepsy.