title: Two novel epilepsy-linked mutations leading to a loss of function of LGI1.
abstract: BACKGROUND
  Mutations in the leucine-rich, glioma-inactivated 1 (LGI1) gene have been implicated in autosomal dominant lateral temporal epilepsy.
  
  
  OBJECTIVE
  To describe the clinical and genetic findings in 2 families with autosomal dominant lateral temporal epilepsy and the functional consequences of 2 novel mutations in LGI1.
  
  
  METHODS
  Clinical, genetic, and functional investigations.
  
  
  METHODS
  University hospital. Patients Two French families with autosomal dominant lateral temporal epilepsy. Main Outcome Measure Mutation analysis.
  
  
  RESULTS
  Two novel disease-linked mutations, p.Leu232Pro and c.431 + 1G>A, were identified in LGI1. We demonstrated that the c.431 + 1G>A mutation causes the deletion of exons 3 and 4 of the LGI1 transcript and showed that the p.Leu232Pro mutation dramatically decreases secretion of the mutant protein by mammalian cells.
  
  
  CONCLUSIONS
  Our data indicate that LGI1 is a secreted protein and suggest that LGI1-related epilepsy results from a loss of function.
authors.affiliation: INSERM UMR 679, Neurologie and Thérapeutique Expérimentale, Université Pierre et Marie Curie-Paris 6, Faculté de Médecine, Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, 47 boulevard de l'hôpital, 75013 Paris, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Chabrol
authors.forename: Cyprian
authors.initials: C
authors.lastname: Popescu
authors.forename: Isabelle
authors.initials: I
authors.lastname: Gourfinkel-An
authors.forename: Oriane
authors.initials: O
authors.lastname: Trouillard
authors.forename: Christel
authors.initials: C
authors.lastname: Depienne
authors.forename: Kristen
authors.initials: K
authors.lastname: Senechal
authors.forename: Michel
authors.initials: M
authors.lastname: Baulac
authors.forename: Eric
authors.initials: E
authors.lastname: LeGuern
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Baulac
mesh_terms: D000328:Adult; D015153:Blotting, Western / Q000379:methods; D004252:DNA Mutational Analysis; D004827:Epilepsy / Q000235:genetics*; D005091:Exons; D005192:Family Health; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007930:Leucine / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011392:Proline / Q000235:genetics; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012720:Severity of Illness Index
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; D011506:Proteins; D012333:RNA, Messenger; D011392:Proline; D007930:Leucine