Potassium current inactivation as a novel pathomechanism for KCNQ2 developmental and epileptic encephalopathy.

ABSTRACT: De novo variants in KCNQ2 cause neonatal onset developmental and epileptic encephalopathy (KCNQ2-DEE; Online Mendelian Inheritance in Man #613720), most often by loss-of-function in vitro effects. In this study, we describe a neonatal onset DEE proband carrying a recurrent de novo KCNQ2 variant (c.794C>T; p.A265V) affecting the pore domain of KCNQ2-encoded Kv7.2 subunits. Whole-cell patch-clamp measurement in a mammalian heterologous expression system revealed that, when compared to wild-type Kv7.2 channels, channels containing Kv7.2 A265V subunits displayed (1) reduced maximal current density; (2) decreased voltage-dependence of activation; and (3) an unusual inactivation process, with a 50% current reduction during 1-2-s depolarizing pulses at voltages > 0 mV. These effects were proporti

SUBMITTER: Gaspar IL 

PROVIDER: S-EPMC12169393 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature