Clinical features and PRRT2 gene mutation in paroxysmal kinesigenic dyskinesia

目的 探讨阵发性运动诱发的运动障碍(PKD)患儿的临床表型和富脯氨酸跨膜蛋白2(PRRT2)基因突变的特点.方法 收集2004年1月至2014年7月在北京大学第一医院儿科神经专业门诊就诊的PKD患儿及其家系成员的临床资料.共入选10例PKD患儿,均为男性,其中4例患儿为4个PKD家系中的先证者,其余6例为散发病例.对患儿的临床资料进行分析,采集患儿及其父母和家系受累成员外周血,采用PCR和Sanger测序的方法筛查PRRT2基因突变.结果 10例患儿的起病年龄为4～13岁,中位起病年龄为10岁.运动障碍表现为运动启动时出现异常姿势或不自主运动,其中表现为肌张力不全5例,舞蹈手足徐动症2例,兼有肌张力不全和舞蹈手足徐动症3例,持续时间为3 ～30 s,发作频率为每月1次至每天20次,发作时意识清楚.4个PKD家系均发现PRRT2基因突变,突变均为c.649_650insC(p.R217PfsX8);6例PKD散发病例中,2例发现有PRRT2基因突变,突变为c.649_650insC(p.R217PfsX8),且突变均遗传自无PKD症状的母亲.结论 PKD患儿的起病年龄可早至幼儿,家系受累者与散发病例临床表型无明显不同,可表现为肌张力不全、舞蹈手足徐动症或二者兼有.PKD家系或PKD散发病例均可由PRRT2基因突变导致,突变c.649_650insC是该基因的热点突变.Objective To investigate the clinical features and proline-rich transmembrane protein 2 (PRRT2) gene mutation in patients with paroxysmal kinesigenic dyskinesia (PKD).Method Clinical information was collected at Peking University First Hospital from January 2004 to July 2014.In total,10 patients with PKD were recruited,and all were males.Among them,four patients were the probands from four PKD families and the other six patients were sporadic cases.Clinical information was analyzed.Peripheral blood samples for DNA study were collected from PKD patients and their family members.Genomic DNA was extracted using standard procedures.Mutation analysis of PRRT2 was performed by Sanger sequencing after PCR.Result Of the 10 patients,the median age of dyskinesias onset was 10 years,ranging from 4 to 13 years.The description of their attacks were abnormal involuntary movements provoked by sudden movements,without loss of consciousness.Five patients exhibited dystonia,two patients exhibited choreoathetosis,and three patients had mixed (dystonia and choreoathetosis) dyskinesias.The duration of the attacks lasted for 3 to 30 seconds.The frequency ranged from once per month to twenty times per day.PRRT2 mutations,c.649_ 650insC (p.R217PfsX8),were found in all the four PKD families.Mutation c.649_650insC was also detected in two of the six sporadic PKD cases,inheriting from their asymptomatic mother.Conclusion The onset age of PKD could be in the early childhood.The clinical features of the familial cases and sporadic cases showed no difference.The attacks manifested as dystonia,choreathetosis,or mixed.PRRT2 mutations could be identified in familial or sporadic cases with PKD.Mutation c.649_650insC is the hotspot mutation of PRRT2 gene.中文核心期刊要目总览(PKU)中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)8621-6255