title: A new locus for generalized epilepsy with febrile seizures plus maps to chromosome 2.
abstract: Generalized epilepsy with febrile seizures plus (GEFS+) is a recently recognized but relatively common form of inherited childhood-onset epilepsy with heterogeneous epilepsy phenotypes. We genotyped 41 family members, including 21 affected individuals, to localize the gene causing epilepsy in a large family segregating an autosomal dominant form of GEFS+. A genomewide search examining 197 markers identified linkage of GEFS+ to chromosome 2, on the basis of an initial positive LOD score for marker D2S294 (Z=4.4, recombination fraction [straight theta] = 0). A total of 24 markers were tested on chromosome 2q, to define the smallest candidate region for GEFS+. The highest two-point LOD score (Zmax=5.29; straight theta=0) was obtained with marker D2S324. Critical recombination events mapped the GEFS+ gene to a 29-cM region flanked by markers D2S156 and D2S311, with the idiopathic generalized epilepsy locus thereby assigned to chromosome 2q23-q31. The existence of the heterogeneous epilepsy phenotypes in this kindred suggests that seizure predisposition determined by the GEFS+ gene on chromosome 2q could be modified by other genes and/or by environmental factors, to produce the different seizure types observed.
authors.affiliation: Centre for Research in Neuroscience, The Montreal General Hospital Research Institute, Montreal Neurological Institute and Hospital, Montreal, Quebec, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Lopes-Cendes
authors.forename: I E
authors.initials: IE
authors.lastname: Scheffer
authors.forename: S F
authors.initials: SF
authors.lastname: Berkovic
authors.forename: M
authors.initials: M
authors.lastname: Rousseau
authors.forename: E
authors.initials: E
authors.lastname: Andermann
authors.forename: G A
authors.initials: GA
authors.lastname: Rouleau
mesh_terms: D017668:Age of Onset; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D004829:Epilepsy, Generalized / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007223:Infant; D008126:Lod Score; D008297:Male; D010375:Pedigree; D010641:Phenotype; D003294:Seizures, Febrile / Q000235:genetics*
chemical_list: D005819:Genetic Markers