title: A second locus for familial generalized epilepsy with febrile seizures plus maps to chromosome 2q21-q33.
abstract: We report a clinical and genetic study of a family with a phenotype resembling generalized epilepsy with febrile seizures plus (GEFS+), described by Berkovic and colleagues. Patients express a very variable phenotype combining febrile seizures, generalized seizures often precipitated by fever at age >6 years, and partial seizures, with a variable degree of severity. Linkage analysis has excluded both the beta 1 subunit gene (SCN1B) of a voltage-gated sodium (Na+) channel responsible for GEFS+ and the two loci, FEB1 and FEB2, previously implicated in febrile seizures. A genomewide search, under the assumption of incomplete penetrance at 85% and a phenocopy rate of 5%, permitted identification of a new locus on chromosome 2q21-q33. The maximum pairwise LOD score was 3.00 at recombination fraction 0 for marker D2S2330. Haplotype reconstruction defined a large (22-cM) candidate interval flanked by markers D2S156 and D2S2314. Four genes coding for different isoforms of the alpha-subunit voltage-gated sodium channels (SCN1A, SCN2A1, SCN2A2, and SCN3A) located in this region are strong candidates for the disease gene.
authors.affiliation: INSERM U289, Hôpital de la Salpêtrière, Paris cedex, France.
authors.forename: S
authors.initials: S
authors.lastname: Baulac
authors.forename: I
authors.initials: I
authors.lastname: Gourfinkel-An
authors.forename: F
authors.initials: F
authors.lastname: Picard
authors.forename: M
authors.initials: M
authors.lastname: Rosenberg-Bourgin
authors.forename: J F
authors.initials: JF
authors.lastname: Prud'homme
authors.forename: M
authors.initials: M
authors.lastname: Baulac
authors.forename: A
authors.initials: A
authors.lastname: Brice
authors.forename: E
authors.initials: E
authors.lastname: LeGuern
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D004829:Epilepsy, Generalized / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005602:France / Q000453:epidemiology; D005819:Genetic Markers / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007223:Infant; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D019683:Penetrance; D003294:Seizures, Febrile / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D015222:Sodium Channels / Q000235:genetics
chemical_list: D005819:Genetic Markers; D015222:Sodium Channels