Autosomal dominant lateral temporal epilepsy in a family exhibiting a rare heterozygous mutation and deletion in the leucine-rich glioma inactivated 1 gene
Autosomal dominant lateral temporal epilepsy in a family exhibiting a rare heterozygous mutation and deletion in the leucine-rich glioma inactivated 1 gene
复制标题
富含亮氨酸的胶质瘤失活 1 基因中表现出罕见杂合突变和缺失的常染色体显性侧颞叶癫痫家族
DOI：
10.1016/j.neulet.2022.136698
复制
发表时间：
2022-05-30
影响因子：
2.5
通讯作者：
Ma，Yuanlin
中科院分区：
文献类型：
--
作者：
Liu，Jie;Hu，Danmei;Ma，Yuanlin
常染色体显性颞侧癫痫 (ADLTE) 是一种由富含亮氨酸的神经胶质瘤失活 1 (LGI1) 基因突变引起的遗传综合征。在一个跨越四代、有六名 ADLTE 患者的家庭中，我们的连锁和外显子组测序研究揭示了 LGI1 (c.1494del(p.Phe498LeufsTer15)) 中罕见的移码杂合突变。使用基因克隆方法创建具有野生型和突变型 LGI1 等位基因的质粒。通过转染 HEK293 细胞和原代神经元，它们被用来评估野生型和突变型 LGI1 的亚细胞位置。此外，还分析了质粒转染的原代神经元的神经元复杂性和树突棘密度。根据我们的结果。该突变降低了转染 HEK293 细胞中 LGI1 的分泌。在初级神经元中，突变的 LGI1 影响神经元的极性和复杂性。我们的研究结果拓宽了 LGI1 突变的表型谱，并提供了有关该突变致病性的证据。此外，我们还发现了有关 LGI1 在颞叶癫痫发展中的作用的新信息，以及神经元极性紊乱和 ADLTE 之间可能存在的联系。
Autosomal dominant lateral temporal epilepsy (ADLTE) is an inherited syndrome caused by mutations in the leucine-rich glioma inactivated 1 (LGI1) gene. In a family with six ADLTE patients spanning four generations, our linkage and exome sequencing investigations revealed a rare frameshift heterozygous mutation inLGI1(c.1494del(p.Phe498LeufsTer15)). Gene cloning methods were used to create plasmids with wild-type and mutantLGI1alleles. Through transfection of HEK293 cells and primary neurons, they were utilized to assess the subcellular location of wild-type and mutant LGI1. Moreover, the plasmid-transfected primary neurons were analyzed for neuronal complexity and density of dendritic spines. According to our results. the mutation decreased LGI1 secretion in transfected HEK293 cells. In primary neurons, mutantLGI1affected neuronal polarity and complexity. Our findings have broadened the phenotypic spectrum ofLGI1mutations and provided evidence regarding the pathogenicity of this mutation. In addition, we discovered new information about the role ofLGI1in the development of temporal lobe epilepsy, along with a possible link between neuronal polarity disorder and ADLTE.