title: Channelopathies as a genetic cause of epilepsy.
abstract: OBJECTIVE
  This review describes the significant number of new gene associations with epilepsy syndromes that have emerged during the past year, together with additional mutations and new electrophysiological data relating to previously known gene associations.
  
  
  RESULTS
  Autosomal dominant juvenile myoclonic epilepsy was demonstrated to be a channelopathy associated with a GABA(A) receptor, alpha1 subunit mutation. Benign familial neonatal infantile seizures were delineated as another channelopathy of infancy, by molecular characterization of sodium channel, alpha2 subunit defects. A sodium channel, alpha2 subunit defect was previously found to be associated with generalized epilepsy with febrile seizures plus. Similarly, the clinical spectrum associated with potassium channel, KQT-like mutations was extended to include the channelopathy myokymia and neonatal epilepsy. Mutations in the non-ion channel genes, leucine-rich, glioma inactivated 1 gene and Aristaless related homeobox gene, have emerged as important causes of their specific syndromes, with mutations in the latter gene frequently underlying X-linked mental retardation with epilepsy.
  
  
  CONCLUSIONS
  All but one of the idiopathic epilepsies with a known molecular basis are channelopathies. Where the ion channel defects have been identified, however, they generally account for a minority of families and sporadic cases with the syndrome in question. The data suggest that ion channel mutations of large effect are a common cause of rare monogenic idiopathic epilepsies, but are rare causes of common epilepsies. Additive effects of genetic variation, perhaps within the same ion channel gene families, are likely to underlie the common idiopathic generalized epilepsies with complex inheritance. The genetics of epilepsy is progressing rapidly toward a more detailed molecular dissection and definition of syndromes.
authors.affiliation: Centre for Medical Genetics, Department of Laboratory Genetics, Women's and Children's Hospital, 72 King William Road, North Adelaide 5006, South Australia. jmulley@bionomics.com.au
authors.forename: John C
authors.initials: JC
authors.lastname: Mulley
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Scheffer
authors.forename: Steven
authors.initials: S
authors.lastname: Petrou
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Berkovic
mesh_terms: D015220:Calcium Channels / Q000235:genetics; D002869:Chromosome Aberrations; D004827:Epilepsy / Q000235:genetics* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D051658:KCNQ2 Potassium Channel; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D062550:NAV1.1 Voltage-Gated Sodium Channel; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D011506:Proteins / Q000235:genetics; D043562:Receptors, G-Protein-Coupled; D011963:Receptors, GABA-A / Q000235:genetics* / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D062547:Voltage-Gated Sodium Channel beta-1 Subunit; D020864:Calcium Channels, N-Type
chemical_list: D015220:Calcium Channels; D018398:Homeodomain Proteins; D051658:KCNQ2 Potassium Channel; D008565:Membrane Proteins; D062550:NAV1.1 Voltage-Gated Sodium Channel; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011506:Proteins; D043562:Receptors, G-Protein-Coupled; D011963:Receptors, GABA-A; D011978:Receptors, Nicotinic; D015222:Sodium Channels; D014157:Transcription Factors; D062547:Voltage-Gated Sodium Channel beta-1 Subunit; C417525:ADGRV1 protein, human; C469264:ARX protein, human; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type; C491367:Cacna1a protein, rat; C120070:CrispId2 protein, rat; C496914:KCNQ2 protein, human; C568242:SCN1A protein, human; C470379:SCN1B protein, human; C568251:SCN2A protein, human; C568250:Scn1a protein, rat; C568253:Scn2A protein, rat