The R207W mutation in the KCNQ2 potassium channel was identified in all affected members of a family with BFNC and myokymia, leading to drastically slowed voltage activation.
Observational
The R207W mutation in KCNQ2 alters channel activation kinetics, providing a mechanistic explanation for the clinical syndrome of BFNC and myokymia.
KCNQ2 and KCNQ3 are two homologous K(+) channel subunits that can combine to form heterotetrameric channels with properties of neuronal M channels. Loss-of-function mutations in either subunit can lead to benign familial neonatal convulsions (BFNC), a generalized, idiopathic epilepsy of the newborn. We now describe a syndrome in which BFNC is followed later in life by myokymia, involuntary contractions of skeletal muscles. All affected members of the myokymia/BFNC family carried a mutation (R207W) that neutralized a charged amino acid in the S4 voltage-sensor segment of KCNQ2. This substitution led to a shift of voltage-dependent activation of KCNQ2 and a dramatic slowing of activation upon depolarization. Myokymia is thought to result from hyperexcitability of the lower motoneuron, and indeed both KCNQ2 and KCNQ3 mRNAs were detected in the anterior horn of the spinal cord where the cells of the lower motoneurons arise. We propose that a difference in firing patterns between motoneurons and central neurons, combined with the drastically slowed voltage activation of the R207W mutant, explains why this particular KCNQ2 mutant causes myokymia in addition to BFNC.
Dedek et al. (2001) conducted an observational in Myokymia and benign familial neonatal convulsions (BFNC). KCNQ2 R207W mutation was evaluated on Electrophysiological properties of the KCNQ2 R207W mutant channel. The R207W mutation in the KCNQ2 potassium channel was identified in all affected members of a family with BFNC and myokymia, leading to drastically slowed voltage activation.
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