title: A newly discovered LGI1 mutation in Korean family with autosomal dominant lateral temporal lobe epilepsy.
abstract: OBJECTIVE
  A new leucine-rich glioma-inactivated 1 gene (LGI1) mutation inducing an amino acid sequence substitution was found in a Korean family with autosomal dominant lateral temporal lobe epilepsy (ADLTE). We report the clinical features and characteristics of this newly identified LGI1 mutation.
  
  
  METHODS
  Clinical data were collected from a large ADLTE family. All exons and flanking regions of the LGI1 gene were directly sequenced. 243 healthy controls were screened for the putative mutation. The 'Sorting Tolerant From Intolerant' algorithm was employed for the prediction of mutated LGI1 protein stability. LGI1 protein secretion was confirmed in vitro by immunoblotting assay.
  
  
  RESULTS
  The main clinical characteristics included a young age at onset (mean, 12.4 years), diverse phenotypic manifestations, the occurrence of generalized tonic-clonic seizures, and a favorable prognosis. The genetic analysis detected a nonsynonymous single nucleotide polymorphism of c.137G>T coding for p.C46F in the five affected family members. This variant was not found in the normal control population and one unaffected family member. All the amino acids substituted for cysteine at position 46 of the LGI1 protein were predicted to damage protein stability in in silico analysis. Mutated C46F protein was retained within the cell at the immunoblotting assay.
  
  
  CONCLUSIONS
  We identified a new LGI1 mutation in a large Korean ADLTE family which appeared to be involved in the development of epilepsy through suppressing LGI1 protein secretion.
authors.affiliation: Department of Neurology, Epilepsy Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Moon Kyu
authors.initials: MK
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, Pharmacogenomic Research Center for Membrane Transporters, Yonsei University College of Medicine, Seoul, Republic of Korea; Brain Korea 21 Project for Medical Science, Yonsei University, Seoul, Republic of Korea.
authors.forename: So Won
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Pharmacogenomic Research Center for Membrane Transporters, Yonsei University College of Medicine, Seoul, Republic of Korea; Research Center for Human Natural Defense System, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Neurology, Epilepsy Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yang-Je
authors.initials: YJ
authors.lastname: Cho
authors.affiliation: Department of Neurology, Epilepsy Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Doh-Eui
authors.initials: DE
authors.lastname: Kim
authors.affiliation: Department of Neurology, Epilepsy Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Byung In
authors.initials: BI
authors.lastname: Lee
authors.affiliation: Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Ho Min
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Pharmacogenomic Research Center for Membrane Transporters, Yonsei University College of Medicine, Seoul, Republic of Korea; Brain Korea 21 Project for Medical Science, Yonsei University, Seoul, Republic of Korea.
authors.forename: Min Goo
authors.initials: MG
authors.lastname: Lee
authors.affiliation: Department of Neurology, Epilepsy Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: kheo@yuhs.ac.
authors.forename: Kyoung
authors.initials: K
authors.lastname: Heo
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D004833:Epilepsy, Temporal Lobe / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017433:Protein Structure, Secondary; D011506:Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; D011506:Proteins
keywords: Clinical features; Genetic analysis; Korean ADLTE family; LGI1; Mutation