Novel loss-of-function PRRT2 mutation causes paroxysmal kinesigenic dyskinesia in a Han Chinese family
Novel loss-of-function PRRT2 mutation causes paroxysmal kinesigenic dyskinesia in a Han Chinese family
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新型 PRRT2 功能丧失突变导致中国汉族家庭阵发性运动诱发性运动障碍。
DOI：
10.1186/1471-2377-14-146
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发表时间：
2014-07-16
期刊：
影响因子：
2.6
通讯作者：
Xiong, Fu
中科院分区：
文献类型：
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作者：
Ji, Zhisong;Su, Quanxi;Xiong, Fu
背景：富含脯氨酸的跨膜蛋白2（PRRT 2）突变是阵发性运动诱发性运动障碍（PKD）的一个原因。本研究对一个中国汉族PKD家系进行PRRT 2基因突变的检测，并探讨其致病机制。桑格测序用于新突变测序。结果：桑格测序结果显示，PRRT 2基因第2外显子存在一个新的突变，即c.186- 187 delGC，为缺失突变，移码突变产生一个截短的蛋白，并在转染的人胚肾（HEK）293细胞中稳定表达。在COS-7细胞与GFP标记的蛋白质的亚细胞定位试验显示，核定位的突变蛋白，而野生型蛋白质定位在膜。共转染HEK 293细胞与野生型和突变表达质粒细胞没有影响mRNA或蛋白质表达从野生型plasmid.Conclusions：我们的研究结果表明，c.186- 187 delGC突变导致PRRT 2基因的截短蛋白参与PKD发病机制与单倍不足。该结果扩展了PRRT 2基因的突变谱，为研究突变的PRRT 2基因的发病机制提供了新的实例。
Background: Mutations in proline-rich transmembrane protein 2 (PRRT2) are a cause of paroxysmal kinesigenic dyskinesia (PKD). In this study, we investigated the PRRT2 gene mutation in a Chinese Han family with PKD and study the pathogenesis of the mutation with PRRT2 gene.Methods: Peripheral venous blood was taken from the family members. Sanger sequencing was used for novel mutation sequencing. For the pathogenesis with the novel mutation was analyzed by bioinformatics, real-time PCR, subcellular localization and Western blot.Results: The Sanger sequencing showed a novel mutation, c.186-187delGC, a deletion mutation, in exon 2 of the PRRT2 gene, the frameshift mutation generated a truncated protein that was stably expressed in transfected Human embryonic kidney (HEK) 293 cells. A subcellular localization assay in COS-7 cells with GFP-tagged protein showed nuclear localization for the mutant protein while the wild-type protein was localized in membranes. Co-transfection of HEK293 cells with wild-type and mutant expression plasmids cells did not influence mRNA or protein expression from the wild-type plasmid.Conclusions: Our findings demonstrated that the c.186-187delGC mutation resulted in a truncated protein from the PRRT2 gene to involve in PKD pathogenesis with haploinsufficiency. The results extend the mutation spectrum of the PRRT2 gene and provide a new example for studying the pathogenesis of the mutated PRRT2 gene.