家族性发作性运动诱发性运动障碍一家系研究
发布时间：2018-10-20 10:19
【摘要】：背景发作性运动诱发性运动障碍(paroxysmal kinesigenic dyskinesia,PKD)是一种临床少见的神经系统疾病,多于儿童及青少年期起病,临床表现为由突然运动、情绪激动等因素诱发的短暂性、反复发作性的运动障碍,典型的包括舞蹈样动作、手足徐动症与肌张力障碍等表现。发作持续时间约数秒至数分钟,间歇期正常,每日一般发作数十次,症状严重者可达上百次。病因学上PKD可分为原发性和继发性。根据原发性发作性运动诱发性运动障碍患者有无家族史又可分为散发性与家族性。现今我们所熟知的发作性运动诱发性运动障碍的概念是在1995年由Demirkiran与Jankovic提出的,但该病具体的病因与发病机制尚未完全明了,存在着多种学说,且各学说之间并未形成共识,还需要进一步的考证。但分子遗传学的进展使越来越多的学者认为PKD与遗传因素有关。随着研究的不断深入,在2011年,我国学者首次报道了富脯氨酸跨膜蛋白2(Proline-rich transmemebrane protein2,PRRT2)基因与发作性运动诱发性运动障碍相关,为PKD的致病基因,这使得我们对PKD有了突破性的认识。PRRT2基因作为PKD的致病基因被发现,可以为此类疾病分子水平诊断提供新的经验和证据,能够提高患者的确诊率,而对于患者的下一代,产前基因检测可很好的预防基因传递。目的对一个家族性发作性运动诱发性运动障碍家系进行临床表型研究,从而对该疾病有更深层次的认识,并对该家系进行基因检测,以期获得新的突变位点,为此类疾病分子水平诊断提供新的经验和证据,并探讨PKD的发病机制。方法1.收集资料本研究收集了在郑州大学第一附属医院神经内科临床诊断为发作性运动诱发性运动障碍的患者及其家族成员的临床资料,对患者的临床症状进行分析,并在取得患者及家属同意的基础上,经郑州大学第一附属医院的伦理委员会批准后,抽取患者及家属外周血行基因检测分析。2.基因组DNA提取采用相关液相捕获试剂盒提取基因组DNA。3.样品文库的制备,然后行文库的质量检测,目标区域捕获实验。4.基因突变分析捕获序列在测序仪上进行高通量测序,随后数据分析。结果1.该家系连续3代发病,Ⅰ_1、Ⅱ_3、Ⅱ_6、Ⅲ_4、Ⅲ_6发病年龄分别为26、17、16、12、10岁,每代发病年龄逐渐提前,病情加重。2.5位患者存在类似的诱发因素及表现,为突然运动后诱发的四肢肌张力障碍,但在同一家系中的患者之间存在不同的临床表型:Ⅰ1发作时伴有言语不能或发音不清的表现;Ⅱ6情绪激动或紧张时也可诱发,并伴有痉挛性斜颈的症状;并;Ⅲ6在体位变化时同样可出现症状。3.Ⅱ3、Ⅱ6、Ⅲ4、Ⅲ6外周血基因测序分析后得出结果:PRRT2基因杂合缺失。4.服用小剂量抗癫痫药物如卡马西平、苯妥英钠的发作性运动诱发性运动障碍的患者,症状均能得到很好的控制。结论1.家族性发作性运动诱发性运动障碍家系存在遗传早现现象,且此疾病存在临床表型异质性或外显不全的可能性。2.PRRT2基因是家族性发作性运动诱发性运动障碍的致病基因,PRRT2基因的杂合缺失可导致家族性发作性运动诱发性运动障碍。3对于临床症状提示发作性运动诱发性运动障碍的患者,在排除了癫痫等相似疾病以及继发性发作性运动诱发性运动障碍的可能性后,可行基因检测以明确诊断。
[Abstract]:Background-onset motion-induced dymosia (PKD) is a rare neurological disorder, more than childhood and adolescence, characterized by transient, repeated seizure disorders induced by sudden movement, emotional agitation, and the like, Typical include dance-like action, hand-foot-foot-xu motion, muscle tension disorder, etc. The duration of the attack is about several seconds to several minutes, the period of onset is normal, and the daily general attack is dozens of times, and the symptoms can reach hundreds of times. PKD can be divided into primary and secondary. The family history of patients with motor dysfunction induced by primary paroxysmal kinesiology can also be divided into family history and familial sex. In 1995, the concept of paroxysmal kinesiology-induced dymosia is presented by Demirkiran and Jankovic in 1995, but the specific etiology and pathogenesis of the disease have not been fully understood, there are many theories, and there is no consensus among the theories, and further textual research is needed. But the progress of molecular genetics has made more and more scholars believe that PKD is related to genetic factors. With the further development of the research, in 2011, Chinese scholars reported for the first time that Proline-rich transmembrane protein2 (PRTR2) gene was associated with paroxysmal kinesitic movement-induced dymosia, and was a pathogenic gene of PKD, which made us a breakthrough in PKD. The PRRT2 gene is found as a pathogenic gene of PKD, can provide new experience and evidence for molecular level diagnosis of such diseases, can improve the diagnosis rate of patients, and can be used for preventing gene transfer for the next generation of patients and pre-production gene detection. Objective To study the clinical phenotype of a familial paroxysmal kinesiologist with a deeper understanding of the disease and to provide new experience and evidence for the molecular level diagnosis of such diseases. The pathogenesis of PKD was discussed. Method 1. The data collected in this study collected clinical data of patients and their family members in the neurology clinic of the First Affiliated Hospital of Zhengzhou University and analyzed the clinical symptoms of the patients, and on the basis of obtaining the consent of the patient and the family, After the approval of the Ethics Committee of the First Affiliated Hospital of Zhengzhou University, the gene detection and analysis of peripheral blood of patients and their families were analyzed. Genomic DNA extraction was performed using an associated liquid phase capture kit to extract genomic DNA. the preparation of a sample library, followed by the quality detection of the library, the target area capture experiment. The gene mutation analysis capture sequence was subjected to high-throughput sequencing on a sequencer, followed by data analysis. Result 1. The onset age of 鈪，
本文编号：2282850
[Abstract]:Background-onset motion-induced dymosia (PKD) is a rare neurological disorder, more than childhood and adolescence, characterized by transient, repeated seizure disorders induced by sudden movement, emotional agitation, and the like, Typical include dance-like action, hand-foot-foot-xu motion, muscle tension disorder, etc. The duration of the attack is about several seconds to several minutes, the period of onset is normal, and the daily general attack is dozens of times, and the symptoms can reach hundreds of times. PKD can be divided into primary and secondary. The family history of patients with motor dysfunction induced by primary paroxysmal kinesiology can also be divided into family history and familial sex. In 1995, the concept of paroxysmal kinesiology-induced dymosia is presented by Demirkiran and Jankovic in 1995, but the specific etiology and pathogenesis of the disease have not been fully understood, there are many theories, and there is no consensus among the theories, and further textual research is needed. But the progress of molecular genetics has made more and more scholars believe that PKD is related to genetic factors. With the further development of the research, in 2011, Chinese scholars reported for the first time that Proline-rich transmembrane protein2 (PRTR2) gene was associated with paroxysmal kinesitic movement-induced dymosia, and was a pathogenic gene of PKD, which made us a breakthrough in PKD. The PRRT2 gene is found as a pathogenic gene of PKD, can provide new experience and evidence for molecular level diagnosis of such diseases, can improve the diagnosis rate of patients, and can be used for preventing gene transfer for the next generation of patients and pre-production gene detection. Objective To study the clinical phenotype of a familial paroxysmal kinesiologist with a deeper understanding of the disease and to provide new experience and evidence for the molecular level diagnosis of such diseases. The pathogenesis of PKD was discussed. Method 1. The data collected in this study collected clinical data of patients and their family members in the neurology clinic of the First Affiliated Hospital of Zhengzhou University and analyzed the clinical symptoms of the patients, and on the basis of obtaining the consent of the patient and the family, After the approval of the Ethics Committee of the First Affiliated Hospital of Zhengzhou University, the gene detection and analysis of peripheral blood of patients and their families were analyzed. Genomic DNA extraction was performed using an associated liquid phase capture kit to extract genomic DNA. the preparation of a sample library, followed by the quality detection of the library, the target area capture experiment. The gene mutation analysis capture sequence was subjected to high-throughput sequencing on a sequencer, followed by data analysis. Result 1. The onset age of 鈪，
本文编号：2282850
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