title: Mutation analysis of the potassium chloride cotransporter KCC3 (SLC12A6) in rolandic and idiopathic generalized epilepsy.
abstract: Genetic predisposition plays a major role in the etiology of idiopathic epilepsies. The common epilepsy syndromes display a complex pattern of inheritance, with an unknown number of genes contributing to seizure susceptibility. During the last decade linkage studies have narrowed down several candidate regions for susceptibility loci of idiopathic epilepsies. Several lines of evidence point to the existence of an epilepsy susceptibility gene on chromosome 15q14. Evidence for linkage to this region has thus been reported for juvenile myoclonic epilepsy, common subtypes of idiopathic generalized epilepsy (IGE), in addition to the EEG trait 'centrotemporal spikes' in families with rolandic epilepsy. The chromosomal region 15q14 harbours several candidate genes that are involved in the regulation of neuronal excitability. One of the most promising candidate genes is the brain-expressed potassium chloride cotransporter KCC3, given that this class of ion transporter has been implicated in the regulation of neuronal chloride activity. We therefore performed a mutation analysis of KCC3 in the index patients of 23 IGE-families as well as of 16 families with rolandic epilepsy which where selected by positive evidence for linkage to D15S165. Four novel single nucleotide exchanges (SNPs) were identified, none of which change the coding sequence. These results do not support a major role for KCC3 in the etiology of rolandic epilepsy or common subtypes of IGE.
authors.affiliation: Institute of Human Genetics, Rheinische Friedrich Wilhelms-Universität, D-53111, Bonn, Germany. ortrud.steinlein@uk.uni-bonn.de
authors.forename: O K
authors.initials: OK
authors.lastname: Steinlein
authors.forename: B A
authors.initials: BA
authors.lastname: Neubauer
authors.forename: T
authors.initials: T
authors.lastname: Sander
authors.forename: L
authors.initials: L
authors.lastname: Song
authors.forename: J
authors.initials: J
authors.lastname: Stoodt
authors.forename: D B
authors.initials: DB
authors.lastname: Mount
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods*; D004829:Epilepsy, Generalized / Q000235:genetics*; D019305:Epilepsy, Rolandic / Q000235:genetics*; D006801:Humans; D027981:Symporters; D000096922:K Cl- Cotransporters
chemical_list: D002352:Carrier Proteins; D027981:Symporters; C119650:SLC12A6 protein, human; D000096922:K Cl- Cotransporters