title: LGI1 mutations in temporal lobe epilepsies.
abstract: OBJECTIVE
  A number of familial temporal lobe epilepsies (TLE) have been recently recognized. Mutations in LGI1 (leucine-rich, glioma-inactivated 1 gene) have been found in a few families with the syndrome of autosomal dominant partial epilepsy with auditory features (ADPEAF). The authors aimed to determine the spectrum of TLE phenotypes with LGI1 mutations, to study the frequency of mutations in ADPEAF, and to examine the role of LGI1 paralogs in ADPEAF without LGI1 mutations.
  
  
  METHODS
  The authors performed a clinical and molecular analysis on 75 pedigrees comprising 54 with a variety of familial epilepsies associated with TLE and 21 sporadic TLE cases. All were studied for mutations in LGI1. ADPEAF families negative for LGI1 mutations were screened for mutations in LGI2, LGI3, and LGI4.
  
  
  RESULTS
  Four families had ADPEAF, 22 had mesial TLE, 11 had TLE with febrile seizures, two had TLE with developmental abnormalities, and 15 had various other TLE syndromes. LGI1 mutations were found in two of four ADPEAF families, but in none of the other 50 families nor in the 21 individuals with sporadic TLE. The mutations were novel missense mutations in exons 1 (c.124T-->G; C42G) and 8 (c.1418C-->T; S473L). No mutations in LGI2, LGI3, or LGI4 were found in the other two ADPEAF families.
  
  
  CONCLUSIONS
  In TLE, mutations in LGI1 are specific for ADPEAF but do not occur in all families. ADPEAF is genetically heterogeneous, but mutations in LGI2, LGI3, or LGI4 did not account for families without LGI1 mutations.
authors.affiliation: Epilepsy Research Institute and Department of Medicine, University of Melbourne, Victoria, Australia. s.berkovic@unimelb.edu.au
authors.forename: S F
authors.initials: SF
authors.lastname: Berkovic
authors.forename: P
authors.initials: P
authors.lastname: Izzillo
authors.forename: J M
authors.initials: JM
authors.lastname: McMahon
authors.forename: L A
authors.initials: LA
authors.lastname: Harkin
authors.forename: A M
authors.initials: AM
authors.lastname: McIntosh
authors.forename: H A
authors.initials: HA
authors.lastname: Phillips
authors.forename: R S
authors.initials: RS
authors.lastname: Briellmann
authors.forename: R H
authors.initials: RH
authors.lastname: Wallace
authors.forename: A
authors.initials: A
authors.lastname: Mazarib
authors.forename: M Y
authors.initials: MY
authors.lastname: Neufeld
authors.forename: A D
authors.initials: AD
authors.lastname: Korczyn
authors.forename: I E
authors.initials: IE
authors.lastname: Scheffer
authors.forename: J C
authors.initials: JC
authors.lastname: Mulley
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D020937:Epilepsy, Partial, Sensory / Q000235:genetics*; D004833:Epilepsy, Temporal Lobe / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005190:Family; D005260:Female; D005799:Genes, Dominant; D005820:Genetic Testing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D051381:Rats; D016415:Sequence Alignment
chemical_list: D016326:Extracellular Matrix Proteins; D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; C456923:LGI2 protein, human; C456924:LGI3 protein, human; C488167:LGI4 protein, human; C492120:Lgi1 protein, mouse; D009419:Nerve Tissue Proteins; D011506:Proteins