Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features
Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features
复制标题
DOI：
10.1038/ng832
复制
发表时间：
2002-03-01
期刊：
影响因子：
30.8
通讯作者：
Gilliam, TC
中科院分区：
文献类型：
--
作者：
Kalachikov, S;Evgrafov, O;Gilliam, TC
癫痫是一种常见的、临床上不同类型的疾病，定义为反复的无缘性癫痫发作(1)。在这里，我们描述了常染色体显性遗传性部分性癫痫伴听觉特征的致病基因的鉴定(ADPEAF，MIM 600512)，这是一种罕见的特发性颞叶外侧癫痫，其特征是部分癫痫发作伴听力障碍(2，3)。我们构建了一个完整的4.2Mb的物理图谱，横跨遗传相关的疾病基因区域，确定了28个推定基因(图1)，并对21个基因的全部或部分进行了重新测序，然后在五个ADPEAF家族中每一个确定了富含亮氨酸、胶质瘤失活的1基因(LGI1)的一个副本的假定突变。先前的研究表明，LGI1的两个拷贝的丢失促进了胶质瘤的进展。我们表明，小鼠Lgi1的表达模式主要是神经元，并与参与颞叶癫痫的解剖区域一致。LGI1作为ADPEAF病因的发现为研究特发性癫痫的发病机制提供了新的途径。
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.