title: Familial temporal lobe epilepsy with psychic auras associated with a novel LGI1 mutation.
abstract: BACKGROUND
  Autosomal dominant lateral temporal epilepsy (ADLTE) is characterized by focal seizures with auditory features or aphasia. Mutations in the LGI1 gene have been reported in up to 50% of ADLTE pedigrees. We report a family with temporal lobe epilepsy characterized by psychic symptoms associated with a novel LGI1 mutation.
  
  
  METHODS
  All participants were personally interviewed and underwent neurologic examination and video-EEG recordings. LGI1 exons were sequenced by standard methods. Mutant cDNA was transfected into human embryonic kidney 293 cells; both cell lysates and media were analyzed by Western blot. In silico modeling of the Lgi1 protein EPTP domain was carried out using the structure of WD repeat protein and manually refined.
  
  
  RESULTS
  Three affected family members were ascertained, 2 of whom had temporal epilepsy with psychic symptoms (déjà vu, fear) but no auditory or aphasic phenomena, while the third had complex partial seizures without any aura. In all patients, we found a novel LGI1 mutation, Arg407Cys, which did not hamper protein secretion in vitro. Mapping of the mutation on a 3-dimensional protein model showed that this mutation does not induce large structural rearrangements but could destabilize interactions of Lgi1 with target proteins.
  
  
  CONCLUSIONS
  The Arg407Cys is the first mutation with no effect on Lgi1 protein secretion. The uncommon, isolated psychic symptoms associated with it suggests that ADLTE encompasses a wider range of auras of temporal origin than hitherto reported.
authors: CNR-Istituto di Neuroscienze, Dipartimento di Scienze Biomediche Sperimentali, Università di Padova, viale G. Colombo 3, 35121 Padova, Italy.
authors: P
authors: P
authors: Striano
authors: G
authors: G
authors: Busolin
authors: L
authors: L
authors: Santulli
authors: E
authors: E
authors: Leonardi
authors: A
authors: A
authors: Coppola
authors: L
authors: L
authors: Vitiello
authors: L
authors: L
authors: Rigon
authors: R
authors: R
authors: Michelucci
authors: S C E
authors: SC
authors: Tosatto
authors: S
authors: S
authors: Striano
authors: C
authors: C
authors: Nobile
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D004252:DNA Mutational Analysis; D004833:Epilepsy, Temporal Lobe / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D005091:Exons; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; D011506:Proteins