Confirming the pathogenicity of NECAP1 in early onset epileptic encephalopathy

Abstract

Early onset epileptic encephalopathy (EOEE) has been used to encompass Ohtahara syndrome (early infantile epileptic encephalopathy [EIEE]), early myoclonic epilepsy, and many others. Multiple genes have been established to cause epileptic encephalopathy in the immature brain, and next-generation sequencing has accelerated the process of novel gene discovery. Many of the previously published candidate genes are still pending confirmatory reports or functional studies. Although most of the genes involved are ion channels (channelopathies), multiple other pathways have been implicated as well. NECAP1 is a key element in clathrin-mediated endocytosis and has been reported previously to cause EOEE in a Saudi family. We report another family with the same variant confirming the pathogenicity of this variant as a Saudi founder mutation, further delineate its phenotype, and propose that it causes EOEE instead of EIEE.