A variant in SLC12A5 for a familial benign Rolandic epilepsy

Benign Rolandic epilepsy (BRE) is the most common cause of epilepsy in childhood. Childhood epilepsies have high heritability, and many BRE cases show an autosomal dominant inheritance pattern. Thanks to the advancement of genomics, the causal genes of BRE were being elucidated. Although BRE is a genetic disorder, most BRE cases cannot be explained by known causal genes. Pleiotropy is a common phenomenon in genes related to epilepsy. For example, the same variant in a gene related to BRE can cause diverse epileptic syndromes from mild BRE to Landau-Kleffner syndrome, a severe form of epilepsy. Although BRE is classified as idiopathic focal epilepsy, BRE can be caused by the same genes or loci related to idiopathic generalized epilepsy (IGE). Using whole exome sequencing, we tried to find causal variants and copy number variations in the known genes for BRE and IGE. We found a novel missense variant in SLC12A5 as a cause of a familial BRE. Although SLC12A5 is a known causal gene for IGE, it may cause BRE, because many genes related to BRE can cause diverse epilepsy syndromes including IGE.