title: Identification of a novel locus for febrile seizures and epilepsy on chromosome 21q22.
abstract: OBJECTIVE
  To report results of linkage analysis in a large family with autosomal dominant (AD) febrile seizures (FS) and epilepsy.
  
  
  BACKGROUND
  AD FS and epilepsy is clinically and genetically a heterogeneous group of epilepsies, frequently inherited. The most notable, generalized epilepsy with febrile seizures plus (GEFS+), is characterized by heterogeneous phenotypes including FS persisting beyond the usual age of remission or coexisting with afebrile seizures. Mutations in three subunits of sodium channel genes and one GABA(A)-receptor subunit gene have been identified in some GEFS+ pedigrees. Six genetic loci for FS have been reported so far, but the molecular basis of FS remains unknown.
  
  
  METHODS
  We identified a five-generation family with 13 individuals affected by FS. Evidence was found for coexisting afebrile seizures in some affected individuals. Evaluation included a detailed history and neurologic examination, as well as collection of DNA. After excluding previously identified loci associated with FS and epilepsy, a genome-wide search was performed.
  
  
  RESULTS
  Two affected individuals reported only a single FS, whereas the other affected individuals had a history of repeated FS. Coexisting afebrile seizures developed in three individuals. The mode of inheritance was consistent with AD inheritance with an incomplete penetrance. Tight linkage to a group of markers on chromosome 21q22 was identified with flanking markers D21S1909 and D21S1444, and maximum 2-point lod score 3.35 for markers D21S1910 and D21S1894. We excluded four ion-channel genes within this 6.5-cM locus as a cause of FS and epilepsy in this family.
  
  
  CONCLUSIONS
  We report a novel locus on chromosome 21q22 for AD FS. Identification of the gene causing epilepsy on chromosome 21q22 will advance our understanding of inherited epilepsy and FS, and possibly other types of epilepsies.
authors.affiliation: Department of Neurology, Vanderbilt University, Nashville, Tennessee 37232-8552, USA. peter.hedera@vanderbilt.edu
authors.forename: Peter
authors.initials: P
authors.lastname: Hedera
authors.forename: Shaochun
authors.initials: S
authors.lastname: Ma
authors.forename: Marcia A
authors.initials: MA
authors.lastname: Blair
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Taylor
authors.forename: Aline
authors.initials: A
authors.lastname: Hamati
authors.forename: Yuki
authors.initials: Y
authors.lastname: Bradford
authors.forename: Bassel
authors.initials: B
authors.lastname: Abou-Khalil
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002675:Child, Preschool; D002874:Chromosome Mapping / Q000706:statistics & numerical data*; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D004827:Epilepsy / Q000453:epidemiology / Q000235:genetics*; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D019683:Penetrance; D003294:Seizures, Febrile / Q000453:epidemiology / Q000235:genetics*
chemical_list: D005819:Genetic Markers