title: Sodium and potassium channel dysfunctions in rare and common idiopathic epilepsy syndromes.
abstract: Mutations in the SCN1A gene are found in up to 80% of individuals with severe myoclonic epilepsy of infancy (SMEI), and mutations in KCNQ2 and KCNQ3 were identified in benign familial neonatal convulsions (BFNC) as well as in single families with Rolandic epilepsy (RE) and idiopathic generalized epilepsies (IGE). This paper summarizes recent findings concerning sodium (SCN1A) and potassium channel (KCNQ2 and KCNQ3) dysfunctions in the pathogenesis of rare and common idiopathic epilepsies (IE). SMEI, severe idiopathic generalized epilepsy of infancy (SIGEI), and myoclonic-astatic epilepsy (MAE) are rare IE. Because of some semeiologic overlap, a comparative analysis of the SCN1A gene performed in 20 patients with MAE and in 18 with SIGEI. This revealed mutations in three subjects with SIGEI only. Since BFNC are over-represented in families with RE, a mutational analysis was performed in 58 families with RE with and without BNFC. This revealed functionally relevant mutations in two index cases with BNFC, and three missense mutations (one resulting in a significantly reduced potassium current amplitude) in three patients with RE, but without BNFC. One KCNQ3 missense variant was also detected in eight out of 455 IGE patients but not in 454 controls, and a silent KCNQ2-SNP was found over-represented in both epilepsy samples. These findings confirm that mutations in the SCN1A gene are mainly involved in the pathogenesis of SMEI, rarely in that of SIGEI, and are commonly not found in patients with MAE. They also demonstrate that sequence variations of the KCNQ2 and KCNQ3 genes may contribute to the etiology of common IE syndromes.
authors.affiliation: Department of Neuropediatrics, Feulgenstr. 12, D-35385 Giessen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hahn
authors.forename: Bernd A
authors.initials: BA
authors.lastname: Neubauer
mesh_terms: D000818:Animals; D001921:Brain / Q000503:physiopathology; D004252:DNA Mutational Analysis; D004827:Epilepsy / Q000235:genetics*; D020936:Epilepsy, Benign Neonatal / Q000235:genetics; D004829:Epilepsy, Generalized / Q000235:genetics; D019305:Epilepsy, Rolandic / Q000235:genetics; D005190:Family; D006801:Humans; D051658:KCNQ2 Potassium Channel / Q000235:genetics* / Q000378:metabolism; D051659:KCNQ3 Potassium Channel / Q000235:genetics* / Q000378:metabolism; D020125:Mutation, Missense; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000502:physiology; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism
chemical_list: D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human; D051659:KCNQ3 Potassium Channel; C496916:KCNQ3 protein, human; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels