Abstract
Early‑onset epileptic encephalopathy (EOEE) represents one of the most severe epilepsies, characterized by recurrent seizures during early infancy, electroencephalogram (EEG) abnormalities and varying degrees of neurodevelopmental delay. The KCNQ2 gene has been reported to have a major role in EOEE. In the present study, a 3‑month‑old female infant from the Chinese Lisu minority with EOEE was analyzed. Detailed clinical evaluations and next‑generation sequencing were performed to investigate the clinical and genetic characteristics of this patient, respectively. Furthermore, the three‑dimensional structure of the mutant protein was predicted by SWISS‑Model and the expression of KCNQ2 protein in the patient was assessed by flow cytometry. It was observed that the patient presented with typical clinical features of EOEE, including repeated non‑febrile seizures and significant EEG abnormalities. A novel heterozygous missense variant c.431G>C (p.R144P) in KCNQ2 was identified in the patient and the genotyping of KCNQ2 in the patient's parents suggested that this variant was de novo. Subsequently, the breakage of hydrogen bonds between certain amino acids was predicted by structural analysis of the mutant protein. Flow cytometric analysis detected a significant reduction buts not complete loss of native KCNQ2 protein expression in the patient (25.1%). In conclusion, a novel variant in KCNQ2 was confirmed as the genetic cause for EOEE in this patient. The present study expanded the pathogenic mutation spectrum of KCNQ2, enhanced the understanding of the molecular pathogenesis of EOEE and provided novel clues for research on the genotype‑phenotype correlation in this disease.