SCN1A pathogenic variants do not have a distinctive blood-derived DNA methylation signature

SCN1A, encoding the sodium channel protein type 1 alpha subunit, is the most implicated gene in epilepsy. Pathogenic loss-of-function variants that result in SCN1A haploinsufficiency cause the most common DEE, known as Dravet syndrome (DS). Pathogenic gain-of-function variants have been found to cause a more severe, early-onset epilepsy syndrome that is distinct from DS. Here, we investigated DNA methylation patterns in these individuals with SCN1A variants. We generated genome-wide DNA methylation data (Illumina EPIC 850K v1 and 935K v2) for individuals with Dravet syndrome due to pathogenic loss-of-function (LOF) variants in SCN1A and individuals with early infantile SCN1A developmental and epileptic encephalopathies.