Two epilepsy-associated mutations at same site in kV1.2 (KCNA2) oppositely affect channel functional expression

Abstract

We report a new variant of KCNA2 from a pediatric patient with early-onset epilepsy and intellectual disability. KCNA2 encodes the pore-forming subunit of voltage-gated potassium channel KV1.2 and the heterozygous mutation causes amino-acid substitution H310Y. H310 is well-conserved among KV channels, located subsequent to the last arginine (R6) of helix S4 in the voltage-sensing domain (VSD). Interestingly, another mutation at the same position (H310R) was previously reported (ClinVar variation ID: 975835) in a patient with epileptic encephalopathy.