Identification of genetic characteristics in pediatric epilepsy with focal cortical dysplasia type 2 using deep whole‐exome sequencing

Abstract Background: Objective Focal cortical dysplasia type 2 (FCD2) is malformations of cortical development that constitutes a common cause of pediatric focal epilepsy. Germline or somatic variants in the mammalian target of rapamycin (mTOR) signaling pathway genes are pathogenesis of FCD2. In this study, whole-exome deep sequencing was performed on dysplastic cortex from focal epilepsy in children to explore genetic characteristic in FCD2. Methods Resected core lesions of FCD2 were confirmed by pathology and peripheral blood from 11 patients were collected. Deep whole-exome sequencing (> 500X) was performed on derived genomic DNA, germline or somatic variants in brain- specific genes were analyzed and identified. Results In 11 patients, a heterozygous pathogenic germline variant of DEPDC5 was identified in one case, while somatic variants were found in four brain samples. The frequencies of the somatic variant allele were 2.52%~5.12%. Somatic variants in AKT3, TSC2 and MTOR (mTOR signaling pathway genes) were found in three samples. Besides, one somatic variant was detected in MED12 which not been reported to associated with FCD2. Conclusion Our study expanded the variant spectrum in the mTOR-GATOR pathway, also detected a somatic variant in MED12 which was potentially associated with FCD 2.