RESUMEN
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.
Asunto(s)
Epilepsia/clasificación , Epilepsia/genética , Canal de Potasio KCNQ2/genética , Canal de Potasio KCNQ3/genética , Mutación , Adolescente , Adulto , Animales , Estudios de Casos y Controles , Preescolar , Análisis Mutacional de ADN , Epilepsia/patología , Femenino , Humanos , Recién Nacido , Masculino , Mutación Missense , Linaje , Síndrome , Xenopus laevisRESUMEN
Peripheral tissue oxygenation has been studied with near-infrared spectroscopy (NIRS) on either the forearm or calf with questionable comparability. The aim was to compare forearm and calf tissue oxygenation in healthy term neonates measured with NIRS. Fractional oxygen extraction, tissue oxygenation index, and mixed venous oxygenation were similar in both extremities, whereas oxygen delivery and oxygen consumption of calf tissue were higher.
