title: Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features.
abstract: The epilepsies are a common, clinically heterogeneous group of disorders defined by recurrent unprovoked seizures. 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 disturbances. 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 Lgi1 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.
authors.affiliation: Columbia Genome Center, Columbia University, 630 W 168 Street, P&S Box 16, New York, New York 10032, USA.
authors.forename: Sergey
authors.initials: S
authors.lastname: Kalachikov
authors.forename: Oleg
authors.initials: O
authors.lastname: Evgrafov
authors.forename: Barbara
authors.initials: B
authors.lastname: Ross
authors.forename: Melodie
authors.initials: M
authors.lastname: Winawer
authors.forename: Christie
authors.initials: C
authors.lastname: Barker-Cummings
authors.forename: Filippo
authors.initials: F
authors.lastname: Martinelli Boneschi
authors.forename: Chang
authors.initials: C
authors.lastname: Choi
authors.forename: Pavel
authors.initials: P
authors.lastname: Morozov
authors.forename: Kamna
authors.initials: K
authors.lastname: Das
authors.forename: Elita
authors.initials: E
authors.lastname: Teplitskaya
authors.forename: Andrew
authors.initials: A
authors.lastname: Yu
authors.forename: Eftihia
authors.initials: E
authors.lastname: Cayanis
authors.forename: Graciela
authors.initials: G
authors.lastname: Penchaszadeh
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Kottmann
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Pedley
authors.forename: W Allen
authors.initials: WA
authors.lastname: Hauser
authors.forename: Ruth
authors.initials: R
authors.lastname: Ottman
authors.forename: T Conrad
authors.initials: TC
authors.lastname: Gilliam
mesh_terms: D000818:Animals; D001304:Auditory Diseases, Central / Q000150:complications / Q000235:genetics*; D001483:Base Sequence; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D004247:DNA; D004827:Epilepsy / Q000150:complications / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009154:Mutation; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; C492120:Lgi1 protein, mouse; D011506:Proteins; D004247:DNA