两个导致LGI1功能丧失的新型癫痫相关突变。
Two novel epilepsy-linked mutations leading to a loss of function of LGI1.
作者信息
Chabrol Elodie, Popescu Cyprian, Gourfinkel-An Isabelle, Trouillard Oriane, Depienne Christel, Senechal Kristen, Baulac Michel, LeGuern Eric, Baulac Stéphanie
机构信息
INSERM UMR 679, Neurologie and Thérapeutique Expérimentale, Université Pierre et Marie Curie-Paris 6, Faculté de Médecine, Assistance Publique-Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, 47 boulevard de l'hôpital, 75013 Paris, France.
出版信息
Arch Neurol. 2007 Feb;64(2):217-22. doi: 10.1001/archneur.64.2.217.
BACKGROUND
Mutations in the leucine-rich, glioma-inactivated 1 (LGI1) gene have been implicated in autosomal dominant lateral temporal epilepsy.
OBJECTIVE
To describe the clinical and genetic findings in 2 families with autosomal dominant lateral temporal epilepsy and the functional consequences of 2 novel mutations in LGI1.
DESIGN
Clinical, genetic, and functional investigations.
SETTING
University hospital. Patients Two French families with autosomal dominant lateral temporal epilepsy. Main Outcome Measure Mutation analysis.
RESULTS
Two novel disease-linked mutations, p.Leu232Pro and c.431 + 1G>A, were identified in LGI1. We demonstrated that the c.431 + 1G>A mutation causes the deletion of exons 3 and 4 of the LGI1 transcript and showed that the p.Leu232Pro mutation dramatically decreases secretion of the mutant protein by mammalian cells.
CONCLUSION
Our data indicate that LGI1 is a secreted protein and suggest that LGI1-related epilepsy results from a loss of function.
背景
富含亮氨酸的胶质瘤失活1（LGI1）基因的突变与常染色体显性遗传性外侧颞叶癫痫有关。
目的
描述2个常染色体显性遗传性外侧颞叶癫痫家系的临床和遗传学发现以及LGI1基因中2种新突变的功能后果。
设计
临床、遗传学和功能研究。
单位
大学医院。患者为2个患有常染色体显性遗传性外侧颞叶癫痫的法国家系。主要观察指标为突变分析。
结果
在LGI1基因中鉴定出2种新的疾病相关突变，即p.Leu232Pro和c.431 + 1G>A。我们证明c.431 + 1G>A突变导致LGI1转录本的外显子3和4缺失，并表明p.Leu232Pro突变显著降低了哺乳动物细胞中突变蛋白的分泌。
结论
我们的数据表明LGI1是一种分泌蛋白，并提示LGI1相关癫痫是由功能丧失引起的。
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