CHRNA4 variant causes paroxysmal kinesigenic dyskinesia and genetic epilepsy with febrile seizures plus?
CHRNA4 variant causes paroxysmal kinesigenic dyskinesia and genetic epilepsy with febrile seizures plus?
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DOI：
10.1016/j.seizure.2018.02.005
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发表时间：
2018-03-01
影响因子：
3
通讯作者：
Jiang, Wen
中科院分区：
文献类型：
--
作者：
Jiang, Yong-li;Yuan, Fang;Jiang, Wen
目的：阵发性运动诱发性运动障碍（PKD）和癫痫被认为有共同的遗传病因。PRRT 2已被确定为这两种疾病的致病基因。本研究的目的是在一个PRRT 2阴性的PKD/GEFS+家系中寻找新的致病基因。方法：收集PKD/GEFS+家系中所有受累和未受累成员的临床资料。分析了所有三名患者的脑部磁共振成像和24 h视频脑电图。采用靶向基因板测序技术检测3例患者和5例正常人基因组DNA中的遗传缺陷。结果：该家系为常染色体显性遗传。结论：CHRNA 4可能是一个新的PKD和GEFS+致病基因。我们的研究扩展了癫痫和运动障碍综合征的基因型表型谱，并提供了PKD和GEFS+之间的遗传连锁。(C)2018年英国癫痫协会由爱思唯尔有限公司出版。保留所有权利。
Purpose: Paroxysmal kinesigenic dyskinesia (PKD) and epilepsy are thought to have a shared genetic etiology. PRRT2 has been identified as a causative gene of both disorders. In this study, we aim to explore the potential novel causative gene in a PRRT2-negative family with three individuals diagnosed with PKD or genetic epilepsy with febrile seizures plus (GEFS+).Methods: Clinical data were collected from all the affected and unaffected members of a PKD/GEFS+ family. The Brain magnetic resonance imaging and 24 h video-EEG of all three affected members were analyzed. Targeted gene-panel sequencing was used to detect the genetic defect in genomic DNAs of three affected and five normal individuals. Co-segregation analysis of putatively pathogenic mutations with the phenotype was carried out in all the family members alive to examine the inheritance status.Results: The inheritance model of this pedigree was autosomal dominant. A novel, fully co-segregated mutation (NM_000744: c.979G > A) in CHRNA4 was identified in the family with three individuals diagnosed with PKD or GEFS+.Conclusions: CHRNA4 may be a novel gene causing of PKD and GEFS+. Our study extends the genotypic phenotypic spectrum of combined epileptic and dyskinetic syndromes, and provides a genetic linkage between PKD and GEFS+. (C) 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.