A Potassium Channel Mutation in Neonatal Human Epilepsy

TLDR

Benign familial neonatal convulsions is an autosomal dominant epilepsy of infancy linked to loci on chromosomes 20q13.3 and 8q24. Positional cloning identified the KCNQ2 potassium channel gene on 20q13.3, which is expressed in brain, and functional expression in Xenopus oocytes produced slowly activating, potassium‑selective currents upon depolarization. A five‑base‑pair insertion in KCNQ2 deletes over 300 amino acids from its C‑terminus, abolishes channel currents, and implicates impaired potassium‑dependent repolarization as the likely cause of BFNC.

Abstract

Benign familial neonatal convulsions (BFNC) is an autosomal dominant epilepsy of infancy, with loci mapped to human chromosomes 20q13.3 and 8q24. By positional cloning, a potassium channel gene ( KCNQ2 ) located on 20q13.3 was isolated and found to be expressed in brain. Expression of KCNQ2 in frog ( Xenopus laevis ) oocytes led to potassium-selective currents that activated slowly with depolarization. In a large pedigree with BFNC, a five–base pair insertion would delete more than 300 amino acids from the KCNQ2 carboxyl terminus. Expression of the mutant channel did not yield measurable currents. Thus, impairment of potassium-dependent repolarization is likely to cause this age-specific epileptic syndrome.