title: Exploration of a putative susceptibility locus for idiopathic generalized epilepsy on chromosome 8p12.
abstract: OBJECTIVE
  A recent genome-wide scan revealed a major susceptibility locus for idiopathic generalized epilepsies (IGEs) in the chromosomal region 8p12 in 32 IGE families without members with juvenile myoclonic epilepsy (JME). This study explored the presence of an IGE locus in the chromosomal region 8p12.
  
  
  METHODS
  Our study included 176 multiplex families of probands with common IGE syndromes. Parametric and nonparametric multipoint linkage analyses were carried out between the IGE trait and six microsatellite polymorphisms encompassing the putative susceptibility locus. To explore the associated phenotype-genotype relation, two distinct subgroups of families were selected by the presence (n = 64) or absence (n = 112) of a family member with JME. To adjust the phenotypic spectrum toward adolescent-onset IGEs, a third subgroup of 28 families without JME was chosen through an IGE proband with seizure onset at age 10-20 years.
  
  
  RESULTS
  Parametric and nonparametric multipoint linkage analyses provided no evidence for linkage between IGE and markers encompassing the putative IGE locus in the chromosomal region 8p12. Furthermore, we found no hint of linkage along the candidate region in any of the three family subgroups.
  
  
  CONCLUSIONS
  We failed to provide evidence for a major IGE locus in the chromosomal region 8p12. On the contrary, these parametric linkage results provide strong evidence against linkage across the candidate region under a broad range of genetic models. If there is a susceptibility locus for IGE in the chromosomal region 8p12, then the size of the effect or the proportion of linked families is too small to detect linkage in the investigated family sample.
authors.affiliation: Epilepsie Genetik Gruppe, Neurologische Klinik, Universitätsklinikum Charité, Humboldt-Universität zu Berlin, Germany. Sanderth@aol.com
authors.forename: Thomas
authors.initials: T
authors.lastname: Sander
authors.forename: Christine
authors.initials: C
authors.lastname: Windemuth
authors.forename: Herbert
authors.initials: H
authors.lastname: Schulz
authors.forename: Kathrin
authors.initials: K
authors.lastname: Saar
authors.forename: Elena
authors.initials: E
authors.lastname: Gennaro
authors.forename: Concetta
authors.initials: C
authors.lastname: Riggio
authors.forename: Amedeo
authors.initials: A
authors.lastname: Bianchi
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Rudolf
authors.forename: Fabienne
authors.initials: F
authors.lastname: Picard
authors.forename: Christine
authors.initials: C
authors.lastname: Bulteau
authors.forename: Anna
authors.initials: A
authors.lastname: Kaminska
authors.forename: Cécile
authors.initials: C
authors.lastname: Cieuta
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Prud'homme
authors.forename: Olivier
authors.initials: O
authors.lastname: Dulac
authors.forename: Louise
authors.initials: L
authors.lastname: Bate
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: Gerrit-Jan
authors.initials: GJ
authors.lastname: de Haan
authors.forename: Guus A M A J
authors.initials: GA
authors.lastname: Janssen
authors.forename: M Gerard
authors.initials: MG
authors.lastname: van Erp
authors.forename: Eduard H J F
authors.initials: EH
authors.lastname: Boezeman
authors.forename: Dick
authors.initials: D
authors.lastname: Lindhout
authors.forename: Armin
authors.initials: A
authors.lastname: Heils
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.forename: Diéter
authors.initials: D
authors.lastname: Janz
mesh_terms: D000328:Adult; D000483:Alleles; D002648:Child; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D018900:Dinucleotide Repeats; D004832:Epilepsy, Absence / Q000235:genetics; D004829:Epilepsy, Generalized / Q000235:genetics*; D004830:Epilepsy, Tonic-Clonic / Q000235:genetics; D005060:Europe; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000145:classification*; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D008957:Models, Genetic; D020190:Myoclonic Epilepsy, Juvenile / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D013577:Syndrome
chemical_list: D005819:Genetic Markers