title: A new locus for familial temporal lobe epilepsy on chromosome 3q.
abstract: BACKGROUND
  Temporal lobe epilepsy (TLE) is a common and heterogeneous focal epilepsy syndrome with a complex etiology, involving both environmental and genetic factors. Several familial forms of TLE have been described, including familial lateral TLE (FLTLE), familial mesial TLE (FMTLE) without hippocampal sclerosis, and FMTLE with hippocampal sclerosis. Mutations have been identified only in the leucine-rich, glioma-inactivated 1 (LGI1) gene on chromosome 10q22-q24 in FLTLE. Several loci have been mapped in families with FMTLE, but responsible genes have not been found. We report clinical evaluation in a large family with FMTLE and a new genetic locus.
  
  
  METHODS
  We conducted a genome-wide scan using 10cM-spaced microsatellite markers on a family with TLE. Seven individuals had TLE without antecedent FS; four other individuals had FS during childhood, but no subsequent epilepsy. Patients with TLE had infrequent simple partial, complex partial and secondarily generalized seizures that generally responded well to treatment. The proband had no hippocampal sclerosis. The mode of inheritance appeared to be autosomal dominant with incomplete penetrance. Linkage analysis was performed using the Genehunter software. Regions with LOD score>1 and those that were poorly informative in the first-pass scan were further genotyped.
  
  
  RESULTS
  Linkage was identified on chromosome 3q25-q26 in a 13cM region flanked by markers D3S1584 and D3S3520, with a peak LOD score of 3.23. This interval does not correspond to any previously known locus for familial epilepsy or FS. KCNAB1, encoding a voltage-gated, shaker-related potassium channel, and NLGN1, encoding a member of a family of neuronal cell surface protein were excluded as disease causing mutations.
  
  
  CONCLUSIONS
  We identified a novel locus for familial TLE with FS, providing additional evidence of the complexity and genetic heterogeneity of familial focal epilepsy.
authors.affiliation: Department of Neurology, ULB-Hôpital Erasme, Brussels, Belgium.
authors.forename: Lyne
authors.initials: L
authors.lastname: Chahine
authors.forename: Bassel
authors.initials: B
authors.lastname: Abou-Khalil
authors.forename: Auli
authors.initials: A
authors.lastname: Siren
authors.forename: Frederick
authors.initials: F
authors.lastname: Andermann
authors.forename: Peter
authors.initials: P
authors.lastname: Hedera
authors.forename: Qing
authors.initials: Q
authors.lastname: Ge
authors.forename: Eva
authors.initials: E
authors.lastname: Andermann
authors.forename: Massimo
authors.initials: M
authors.lastname: Pandolfo
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004569:Electroencephalography; D004833:Epilepsy, Temporal Lobe / Q000151:congenital* / Q000235:genetics; D005190:Family; D005260:Female; D056726:Genetic Association Studies; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D007223:Infant; D008126:Lod Score; D008279:Magnetic Resonance Imaging; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D010375:Pedigree; D012640:Seizures / Q000503:physiopathology; D055815:Young Adult
chemical_list: D004247:DNA
keywords: Genetics; Linkage analysis; Temporal lobe epilepsy