Functional evaluation of epilepsy associated KCNT1 variants in multiple cellular systems reveals a predominant gain of function impact on channel properties.

This study represents the largest systematic functional examination of KCNT1 variants to date. We confirm both previously reported GOF channel phenotypes and expand the number of variants with in vitro GOF effects. Our data provide further evidence that novel KCNT1 variants identified in epilepsy patients lead to disease through generalizable GOF mechanisms including increases in current magnitude and/or current voltage relationships.