• Moon Kyu Lee, So Won Kim, Ji Hyun Lee, Yang-Je Cho, Doh-Eui Kim, Byung In Lee, Ho Min Kim, Min Goo Lee, and Kyoung Heo.
• Department of Neurology, Epilepsy Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
• Seizure. 2014 Jan 1; 23 (1): 69-73.

PurposeA 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.MethodsClinical 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.ResultsThe 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.ConclusionWe 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.Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

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