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Identification of novel gene variants in children with drug-resistant epilepsy: Expanding the genetic spectrum

      Abstract

      Background

      Resistance to anti-seizure drugs is an important problem in the treatment of individuals with epilepsy. Identifying the molecular etiology of drug-resistant epilepsy (DRE) is crucial for better management of epilepsy. Here, we explore the utility of whole exome sequencing (WES) to identify causative gene variants in children with DRE.

      Methods

      Forty-five children with DRE who underwent WES tests were included. Genetic examination of all patients included chromosomal analysis and clinical chromosomal microarray followed by WES. The identified variants by WES analysis were classified for pathogenicity based on the American College of Medical Genetics and Genomics guidelines and in silico protein prediction tools.

      Results

      The overall diagnostic yield was 55.5% (25/45). A total of 26 variants spanning 22 genes were identified in 25 patients. Of note, only 19 of these genes were examined as novel. Ten patients (22.2%) had a pathogenic or likely pathogenic variant. There was a trend associated with a diagnostic genetic test result in girls compared to boys in DRE (p=0.028).

      Conclusion

      Our findings expand the mutational spectrum of genes related to DRE. In order to form disease-specific treatment in children with DRE, the WES analysis should be included in the diagnostic algorithm because of its high diagnostic efficiency.

      Keywords

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