title: A novel locus for generalized epilepsy with febrile seizures plus in French families.
abstract: BACKGROUND
  Generalized epilepsy with febrile seizures plus (GEFS(+)) is a familial autosomal dominant entity characterized by the association of febrile and afebrile seizures. Mutations in 3 genes--the sodium channel alpha1 subunit gene (SCN1A), the sodium channel beta1 subunit gene (SCN1B), and the gamma2 GABA receptor subunit gene (GABRG2)--and linkage to 2 other loci on 2p24 and 21q22 have been identified in families with GEFS(+), indicating genetic heterogeneity.
  
  
  OBJECTIVE
  To localize by means of linkage analysis a new gene for GEFS(+) in a large family with 11 affected members and to test the new locus in 4 additional families with GEFS(+).
  
  
  METHODS
  Family-based linkage analysis.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Five French families with GEFS(+) and at least 7 available affected members with autosomal dominant transmission. All the patients had febrile seizures and/or afebrile generalized tonic-clonic seizures or absence epilepsy.
  
  
  METHODS
  We analyzed 380 microsatellite markers and conducted linkage analysis.
  
  
  RESULTS
  In the largest family, a 10-cM-density genomewide scan revealed linkage to a 13-Mb (megabase) interval on chromosome 8p23-p21 with a maximum pairwise logarithm of odds (LOD) score of 3.00 (at Theta = 0) for markers D8S351 and D8S550 and a multipoint LOD score of 3.23. A second family with GEFS(+) was also possibly linked to chromosome 8p23-p21 and the region was narrowed to a 7.3-Mb candidate interval, flanked by markers D8S1706 and D8S549. We have not, so far, identified mutations in the coding exons of 6 candidate genes (MTMR9, MTMR7, CTSB, SGCZ, SG223, and ATP6V1B2) located in the genetic interval.
  
  
  CONCLUSIONS
  We report a sixth locus for GEFS(+) on chromosome 8p23-p21. Because no ion channel genes are located in this interval, identification of the responsible gene will probably uncover a new mechanism of pathogenesis for GEFS(+).
authors.affiliation: INSERM, UMR679, Neurologie and Thérapeutique Expérimentale, UPMC Univ Paris 06, Groupe Hospitalier Pitié-Salpêtrière, 47 boulevard de l'hôpital, 75013 Paris, France. baulac@ccr.jussieu.fr
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Baulac
authors.forename: Isabelle
authors.initials: I
authors.lastname: Gourfinkel-An
authors.forename: Philippe
authors.initials: P
authors.lastname: Couarch
authors.forename: Christel
authors.initials: C
authors.lastname: Depienne
authors.forename: Anna
authors.initials: A
authors.lastname: Kaminska
authors.forename: Olivier
authors.initials: O
authors.lastname: Dulac
authors.forename: Michel
authors.initials: M
authors.lastname: Baulac
authors.forename: Eric
authors.initials: E
authors.lastname: LeGuern
authors.forename: Rima
authors.initials: R
authors.lastname: Nabbout
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D004829:Epilepsy, Generalized / Q000150:complications / Q000235:genetics*; D005260:Female; D005602:France; D008040:Genetic Linkage / Q000235:genetics; D005819:Genetic Markers; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D040641:Quantitative Trait Loci / Q000235:genetics*; D003294:Seizures, Febrile / Q000150:complications / Q000235:genetics*
chemical_list: D005819:Genetic Markers