title: Exploration of the genetic architecture of idiopathic generalized epilepsies.
abstract: OBJECTIVE
  Idiopathic generalized epilepsy (IGE) accounts for approximately 20% of all epilepsies and affects about 0.2% of the general population. The etiology of IGE is genetically determined, but the complex pattern of inheritance suggests an involvement of a large number of susceptibility genes. The objective of the present study was to explore the genetic architecture of common IGE syndromes and to dissect out susceptibility loci predisposing to absence or myoclonic seizures.
  
  
  METHODS
  Genome-wide linkage scans were performed in 126 IGE-multiplex families of European origin ascertained through a proband with idiopathic absence epilepsy or juvenile myoclonic epilepsy. Each family had at least two siblings affected by IGE. To search for seizure type-related susceptibility loci, linkage analyses were carried out in family subgroups segregating either typical absence seizures or myoclonic and generalized tonic-clonic seizures on awakening.
  
  
  RESULTS
  Nonparametric linkage scans revealed evidence for complex and heterogeneous genetic architectures involving linkage signals at 5q34, 6p12, 11q13, 13q22-q31, and 19q13. The signal patterns differed in their composition, depending on the predominant seizure type in the families.
  
  
  CONCLUSIONS
  Our results are consistent with heterogeneous configurations of susceptibility loci associated with different IGE subtypes. Genetic determinants on 11q13 and 13q22-q31 seem to predispose preferentially to absence seizures, whereas loci on 5q34, 6p12, and 19q13 confer susceptibility to myoclonic and generalized tonic-clonic seizures on awakening.
authors.affiliation: Gene Mapping Center, Max-Delbrück Center, Berlin, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Hempelmann
authors.forename: Kirsten P
authors.initials: KP
authors.lastname: Taylor
authors.forename: Armin
authors.initials: A
authors.lastname: Heils
authors.forename: Susanne
authors.initials: S
authors.lastname: Lorenz
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Prud'homme
authors.forename: Rima
authors.initials: R
authors.lastname: Nabbout
authors.forename: Olivier
authors.initials: O
authors.lastname: Dulac
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Rudolf
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
authors.forename: Amedeo
authors.initials: A
authors.lastname: Bianchi
authors.forename: Robert
authors.initials: R
authors.lastname: Robinson
authors.forename: R Mark
authors.initials: RM
authors.lastname: Gardiner
authors.forename: Athanasios
authors.initials: A
authors.lastname: Covanis
authors.forename: Dick
authors.initials: D
authors.lastname: Lindhout
authors.forename: Ulrich
authors.initials: U
authors.lastname: Stephani
authors.forename: Christian E
authors.initials: CE
authors.lastname: Elger
authors.forename: Yvonne G
authors.initials: YG
authors.lastname: Weber
authors.forename: Holger
authors.initials: H
authors.lastname: Lerche
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Kron
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Scheffer
authors.forename: John C
authors.initials: JC
authors.lastname: Mulley
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Berkovic
authors.forename: Thomas
authors.initials: T
authors.lastname: Sander
mesh_terms: D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D004831:Epilepsies, Myoclonic / Q000235:genetics; D004832:Epilepsy, Absence / Q000235:genetics; D004829:Epilepsy, Generalized / Q000235:genetics*; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D044465:White People / Q000235:genetics