Novel nonsense mutation in gene identified by whole-genome sequencing in infant with epilepsy disorder: A case report.

Epilepsy is one of the most common neurological disorders affecting approximately 50 million people worldwide. It impacts people of all genders and ages, but evidence suggests a higher incidence rate in children and the elderly. Given that childhood epilepsy has the risk of causing developmental epileptic encephalopathy, which is associated with intellectual, behavioral, and/or motor disabilities, proper assessment of children with new-onset epilepsy at an early stage is essential to prevent threats affecting neurodevelopmental processes. The aim of this study was to investigate whole genome sequencing data of children diagnosed with epilepsy. Our results revealed an identification of a novel mutation in a 2-year-old male patient who suffered from recurrent epileptic seizures of unknown etiology. The detected variant is heterozygous and located in gene (chr8:27321348, NM_000742, c.612G > A, p.Trp204∗) in exon 6. The databases such as Varsome, GeneCards, and NCBI did not reveal any matches with previously identified variants, implying the novelty of the finding. Moreover, according to various prediction tools (MutationTaster, SIFT, CADD, FATHMM-MKL, LRT, DANN, Eigen, and BayesDel), the mutation is characterized as pathogenic, which corresponds to the American College of Medical Genetics and Genomics (ACMG) classification. According to the findings, mutation of the gene is closely associated with two disorders known as autosomal dominant nocturnal frontal epilepsy (ADNFLE), and benign familial infantile epilepsy (BFIS). Comparison of proband's clinical manifestations showed that it is difficult to attribute precisely the patient's symptoms to either of the conditions, however the evidence suggests that the patient's symptoms are more consistent with those of ADNFLE. In this report, we expanded the spectrum of existing variations in the gene contributing and associated with the development of epilepsy with the important and novel causative genetic variant.