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

被引:464
作者
Kalachikov, S
Evgrafov, O
Ross, B
Winawer, M
Barker-Cummings, C
Boneschi, FM
Choi, C
Morozov, P
Das, K
Teplitskaya, E
Yu, A
Cayanis, E
Penchaszadeh, G
Kottmann, AH
Pedley, TA
Hauser, WA
Ottman, R
Gilliam, TC
机构
[1] Columbia Univ, Gertrude H Sergievsky Ctr, New York, NY 10032 USA
[2] Columbia Univ, Columbia Genome Ctr, New York, NY 10032 USA
[3] Columbia Univ, Dept Epidemiol, New York, NY 10032 USA
[4] Columbia Univ, Dept Psychiat, New York, NY 10032 USA
[5] Columbia Univ, Dept Neurol, New York, NY 10032 USA
[6] Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA
[7] New York State Psychiat Inst & Hosp, Dept Epidemiol Brain Disorders, New York, NY 10032 USA
[8] New York State Psychiat Inst & Hosp, Dept Med Genet, New York, NY 10032 USA
[9] PsychoGenics Inc, New York, NY USA
关键词
D O I
10.1038/ng832
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The epilepsies are a common, clinically heterogeneous group of disorders defined by recurrent unprovoked seizures(1). 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(2,3). 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 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.
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页码:335 / 341
页数:7
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