Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features

Sergey Kalachikov, Oleg Evgrafov, Barbara Ross, Melodie Winawer, Christie Barker-Cummings, Filippo Martinelli Boneschi, Chang Choi, Pavel Morozov, Kamna Das, Elita Teplitskaya, Andrew Yu, Eftihia Cayanis, Graciela Penchaszadeh, Andreas H. Kottmann, Timothy A. Pedley, W. Allen Hauser, Ruth Ottman, T. Conrad Gilliam

Research output: Contribution to journalArticlepeer-review

531 Scopus citations

Abstract

The epilepsies are a common, clinically heterogeneous group of disorders defined by recurrent unprovoked seizures1. Here we describe identification of the causative gene in autosomal-dominant partial epilepsy with auditory features (ADPEAF, MIM 600512), a rare form of idiopathic lateral temporal lobe epilepsy characterized by partial seizures with auditory disturbances2, 3. We constructed a complete, 4.2-Mb physical map across the genetically implicated disease-gene region, identified 28 putative genes (Fig. 1) and resequenced all or part of 21 genes before identifying presumptive mutations in one copy of the leucine-rich, glioma-inactivated 1 gene (LGI1) in each of five families with ADPEAF. Previous studies have indicated that loss of both copies of LGI1 promotes glial tumor progression. We show that the expression pattern of mouse Lgil is predominantly neuronal and is consistent with the anatomic regions involved in temporal lobe epilepsy. Discovery of LGI1 as a cause of ADPEAF suggests new avenues for research on pathogenic mechanisms of idiopathic epilepsies.

Original languageEnglish (US)
Pages (from-to)335-341
Number of pages7
JournalNature genetics
Volume30
Issue number3
DOIs
StatePublished - Mar 2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics

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