OBJECTIVE: To explore the involvement of M-type potassium channels KCNQ2, Q3, 
and Q5 in the pathogenesis of common idiopathic epilepsies.
METHODS: Sequence analysis of the KCNQ2, Q3, and Q5 coding regions was performed 
in a screening sample consisting of 58 nuclear families with rolandic epilepsy. 
Subsequently, an association study was conducted for all discovered variants in 
a case-control sample comprising 459 German patients with idiopathic generalized 
epilepsy (IGE) and 462 population controls.
RESULTS: An in-frame deletion of codon 116 in KCNQ2 (p.Lys116del) and a missense 
mutation in KCNQ3 (p.Glu299Lys) were detected in two index cases exhibiting 
rolandic epilepsy and benign neonatal convulsions. Both mutations resulted in 
reduced potassium current amplitude in Xenopus oocytes. Mutation analysis of 
families with rolandic epilepsy without neonatal seizures discovered three novel 
missense variations (KCNQ2 p.Ile592Met, KCNQ3 p.Ala381Val, KCNQ3 p.Pro574Ser). 
The KCNQ2 p.Ile592Met variant displayed a significant reduction of potassium 
current amplitude in Xenopus oocytes and was present only once in 552 controls. 
Both missense variants identified in KCNQ3 (p.Ala381Val and p.Pro574Ser) were 
present in all affected family members and did not occur in controls, but did 
not show obvious functional abnormalities. The KCNQ3 missense variant 
p.Pro574Ser was also detected in 8 of 455 IGE patients but not in 454 controls 
(p = 0.008). In KCNQ2, a silent single nucleotide polymorphism (rs1801545) was 
found overrepresented in both epilepsy samples (IGE, p = 0.004).
CONCLUSION: Sequence variations of the KCNQ2 and KCNQ3 genes may contribute to 
the etiology of common idiopathic epilepsy syndromes.