Molecular analysis of a mutation in the S5-H5 linker of the KCNQ2 K+ channel causing neonatal convulsions

Benign familial neonatal convulsions (BFNC) are caused by mutations within the two delayed rectifier potassium channels KCNQ2 and KCNQ3. We report here the first BFNC missense mutation located in an extracellular loop of KCNQ2. The mutation, identified in a Turkish BFNC family, predicts the single amino acid substitution, N258S, located in the region linking transmembrane segment S5 to the pore loop. Functional studies in Chinese hamster ovary (CHO) cells, using the patch clamp technique, revealed barely measurable currents when the mutant channel was expressed alone. However, expression of N258S with KCNQ3, led…