title: Genome search for susceptibility loci of common idiopathic generalised epilepsies.
abstract: Genetic factors play a major role in the aetiology of idiopathic generalised epilepsies (IGEs). The present genome scan was designed to identify susceptibility loci that predispose to a spectrum of common IGE syndromes. Our collaborative study included 130 IGE-multiplex families ascertained through a proband with either an idiopathic absence epilepsy or juvenile myoclonic epilepsy, and one or more siblings affected by an IGE trait. In total, 413 microsatellite polymorphisms were genotyped in 617 family members. Non-parametric multipoint linkage analysis, using the GeneHunter program, provided significant evidence for a novel IGE susceptibility locus on chromosome 3q26 (Z(NPL) = 4.19 at D3S3725; P = 0.000017) and suggestive evidence for two IGE loci on chromosome 14q23 (Z(NPL) = 3.28 at D14S63; P = 0.000566), and chromosome 2q36 (Z(NPL) = 2.98 at D2S1371; P = 0.000535). The present linkage findings provide suggestive evidence that at least three genetic factors confer susceptibility to generalised seizures in a broad spectrum of IGE syndromes. The chromosomal segments identified harbour several genes involved in the regulation of neuronal ion influx which are plausible candidates for mutation screening.
authors.affiliation: Epilepsy Genetics Group, Department of Neurology, University Hospital Charité, Humboldt University of Berlin, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Sander
authors.forename: H
authors.initials: H
authors.lastname: Schulz
authors.forename: K
authors.initials: K
authors.lastname: Saar
authors.forename: E
authors.initials: E
authors.lastname: Gennaro
authors.forename: M C
authors.initials: MC
authors.lastname: Riggio
authors.forename: A
authors.initials: A
authors.lastname: Bianchi
authors.forename: F
authors.initials: F
authors.lastname: Zara
authors.forename: D
authors.initials: D
authors.lastname: Luna
authors.forename: C
authors.initials: C
authors.lastname: Bulteau
authors.forename: A
authors.initials: A
authors.lastname: Kaminska
authors.forename: D
authors.initials: D
authors.lastname: Ville
authors.forename: C
authors.initials: C
authors.lastname: Cieuta
authors.forename: F
authors.initials: F
authors.lastname: Picard
authors.forename: J F
authors.initials: JF
authors.lastname: Prud'homme
authors.forename: L
authors.initials: L
authors.lastname: Bate
authors.forename: A
authors.initials: A
authors.lastname: Sundquist
authors.forename: R M
authors.initials: RM
authors.lastname: Gardiner
authors.forename: G A
authors.initials: GA
authors.lastname: Janssen
authors.forename: G J
authors.initials: GJ
authors.lastname: de Haan
authors.forename: D G
authors.initials: DG
authors.lastname: Kasteleijn-Nolst-Trenité
authors.forename: A
authors.initials: A
authors.lastname: Bader
authors.forename: D
authors.initials: D
authors.lastname: Lindhout
authors.forename: O
authors.initials: O
authors.lastname: Riess
authors.forename: T F
authors.initials: TF
authors.lastname: Wienker
authors.forename: D
authors.initials: D
authors.lastname: Janz
authors.forename: A
authors.initials: A
authors.lastname: Reis
mesh_terms: D002883:Chromosomes, Human, Pair 14; D002889:Chromosomes, Human, Pair 2; D002893:Chromosomes, Human, Pair 3; D004829:Epilepsy, Generalized / Q000235:genetics*; D005192:Family Health; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D008126:Lod Score; D018895:Microsatellite Repeats; D020190:Myoclonic Epilepsy, Juvenile / Q000235:genetics; D011110:Polymorphism, Genetic