Sequence variations in KCNQ2 and KCNQ3, including the KCNQ3 p.Pro574Ser variant found in 8 of 455 patients versus 0 of 454 controls (p=0.008), contribute to idiopathic epilepsy syndromes.
Case-Control (n=921)
Do KCNQ2 and KCNQ3 mutations contribute to the pathogenesis of common idiopathic epilepsies?
Sequence variations in the KCNQ2 and KCNQ3 genes are associated with common idiopathic epilepsy syndromes.
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.
Neubauer et al. (Mon,) conducted a case-control in Idiopathic epilepsy syndromes (n=921). KCNQ2, KCNQ3, and KCNQ5 sequence variations vs. Population controls was evaluated on Frequency of KCNQ2, KCNQ3, and KCNQ5 variants. Sequence variations in KCNQ2 and KCNQ3, including the KCNQ3 p.Pro574Ser variant found in 8 of 455 patients versus 0 of 454 controls (p=0.008), contribute to idiopathic epilepsy syndromes.