Exome sequencing identifies truncating mutations in PRRT2 that cause paroxysmal kinesigenic dyskinesia
Exome sequencing identifies truncating mutations in PRRT2 that cause paroxysmal kinesigenic dyskinesia
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DOI：
10.1038/ng.1008
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发表时间：
2011-12-01
期刊：
影响因子：
30.8
通讯作者：
Wu, Zhi-Ying
中科院分区：
文献类型：
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作者：
Chen, Wan-Jin;Lin, Yu;Wu, Zhi-Ying
阵发性运动诱发性运动障碍是阵发性运动障碍中最常见的类型，临床上常误诊为癫痫。采用全外显子测序和桑格测序技术，我们在8个有阵发性运动诱发性运动障碍病史的中国汉族家系中发现了PRRT 2（NM_145239.2）内的3个截短突变：1个家系中的c.514_517delTCTG（p.Ser172Argfs*3），6个家系中的c.649dupC（p.Arg217Profs*8）和1个家系中的c.972delA（p.Val325Serfs*12）。这些截短突变与这些家族中的疾病完全分离，并且在1,000名匹配血统的对照受试者中未观察到。PRRT 2是一个新发现的基因，由4个外显子组成，编码富含脯氨酸的跨膜蛋白2，其包含340个氨基酸，并含有两个预测的跨膜结构域。PRRT 2在发育中的神经系统中高度表达，截短突变改变了PRRT 2蛋白的亚细胞定位。PRRT 2的功能及其在阵发性运动诱发性运动障碍中的作用有待进一步研究。
Paroxysmal kinesigenic dyskinesia is the most common type of paroxysmal movement disorder and is often misdiagnosed clinically as epilepsy. Using whole-exome sequencing followed by Sanger sequencing, we identified three truncating mutations within PRRT2 (NM_145239.2) in eight Han Chinese families with histories of paroxysmal kinesigenic dyskinesia: c.514_517delTCTG (p.Ser172Argfs*3) in one family, c.649dupC (p.Arg217Profs*8) in six families and c.972delA (p.Val325Serfs*12) in one family. These truncating mutations co-segregated exactly with the disease in these families and were not observed in 1,000 control subjects of matched ancestry. PRRT2 is a newly discovered gene consisting of four exons encoding the proline-rich transmembrane protein 2, which encompasses 340 amino acids and contains two predicted transmembrane domains. PRRT2 is highly expressed in the developing nervous system, and a truncating mutation alters the subcellular localization of the PRRT2 protein. The function of PRRT2 and its role in paroxysmal kinesigenic dyskinesia should be further investigated.