Case report: Whole-exome sequencing reveals a novel variant in a patient with epilepsy presenting with fever

Epilepsy is a prevalent neurological disorder characterized by recurrent seizures and significant impacts on quality of life. This case report describes a 2-year-old male patient presenting with epilepsy associated with fever, in whom whole-exome sequencing (WES) revealed a novel de novo variant in the KCNMA1 gene, resulting in the amino acid substitution p.Leu187His. This variant is classified as likely pathogenic and is situated within a key functional domain of the BK channel, a crucial regulator of neuronal excitability. In silico analyses suggest that the substitution alters the local hydrophobicity and may disrupt the channel's function, potentially contributing to the patient's seizure activity. Additionally, the identification of this genetic variant underscores the importance of genetic factors in epilepsy, particularly in cases of drug-resistant epilepsy (DRE) or those with unclear etiology. The findings highlight the utility of WES in diagnosing genetically mediated epilepsy and the need for further research to establish comprehensive genotype-phenotype correlations, ultimately guiding personalized treatment strategies for affected individuals.