title: Molecular basis of Mendelian idiopathic epilepsies.
abstract: A genetic aetiology is estimated to be present in about 40% of patients with epilepsy. Significant progress has been made in understanding the molecular genetic basis of Mendelian epilepsies. Fourteen genes have been identified which underlie a group of rare, autosomal dominant Mendelian idiopathic epilepsies. All but two of these genes encode subunits of ion-channels, revealing that idiopathic Mendelian human epilepsies are predominantly channelopathies. The two non-ion-channel genes, LGl1 causing autosomal dominant lateral temporal lobe epilepsy and MASS1 causing febrile and afebrile seizures, both contain a novel repeat motif variously called the epilepsy-associated repeat (EAR) and epitempin (EPTP) repeat. This motif defines a subfamily of genes, some of which have also been implicated in epilepsy in mice and humans. Progress in dissecting the more common 'complex' genetic epilepsies remains slow, but ion channels represent the most biologically plausible candidates. Characterization of common population sequence variants for the entire cohort of ion channel genes and the development of high-throughput techniques should enable rapid advances in the understanding of the common idiopathic familial epilepsies.
authors.affiliation: Department of Paediatrics and Child Health, Royal Free and University College Medical School, University College London, London, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Robinson
authors.forename: Mark
authors.initials: M
authors.lastname: Gardiner
mesh_terms: D002879:Chromosomes, Human, Pair 10; D004827:Epilepsy / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007473:Ion Channels / Q000235:genetics; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D011506:Proteins / Q000235:genetics; D018079:Receptors, GABA / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics; D062548:Voltage-Gated Sodium Channel beta-2 Subunit
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D007473:Ion Channels; D009419:Nerve Tissue Proteins; D011506:Proteins; D018079:Receptors, GABA; D011978:Receptors, Nicotinic; D015222:Sodium Channels; D062548:Voltage-Gated Sodium Channel beta-2 Subunit; C447159:CHRNB4 protein, human; C116499:LGI1 protein, human; C117620:SCN2B protein, human