家族性發(fā)作性運(yùn)動(dòng)誘發(fā)性運(yùn)動(dòng)障礙一家系研究
發(fā)布時(shí)間：2018-10-20 10:19
【摘要】：背景發(fā)作性運(yùn)動(dòng)誘發(fā)性運(yùn)動(dòng)障礙(paroxysmal kinesigenic dyskinesia,PKD)是一種臨床少見(jiàn)的神經(jīng)系統(tǒng)疾病,多于兒童及青少年期起病,臨床表現(xiàn)為由突然運(yùn)動(dòng)、情緒激動(dòng)等因素誘發(fā)的短暫性、反復(fù)發(fā)作性的運(yùn)動(dòng)障礙,典型的包括舞蹈樣動(dòng)作、手足徐動(dòng)癥與肌張力障礙等表現(xiàn)。發(fā)作持續(xù)時(shí)間約數(shù)秒至數(shù)分鐘,間歇期正常,每日一般發(fā)作數(shù)十次,癥狀嚴(yán)重者可達(dá)上百次。病因?qū)W上PKD可分為原發(fā)性和繼發(fā)性。根據(jù)原發(fā)性發(fā)作性運(yùn)動(dòng)誘發(fā)性運(yùn)動(dòng)障礙患者有無(wú)家族史又可分為散發(fā)性與家族性�，F(xiàn)今我們所熟知的發(fā)作性運(yùn)動(dòng)誘發(fā)性運(yùn)動(dòng)障礙的概念是在1995年由Demirkiran與Jankovic提出的,但該病具體的病因與發(fā)病機(jī)制尚未完全明了,存在著多種學(xué)說(shuō),且各學(xué)說(shuō)之間并未形成共識(shí),還需要進(jìn)一步的考證。但分子遺傳學(xué)的進(jìn)展使越來(lái)越多的學(xué)者認(rèn)為PKD與遺傳因素有關(guān)。隨著研究的不斷深入,在2011年,我國(guó)學(xué)者首次報(bào)道了富脯氨酸跨膜蛋白2(Proline-rich transmemebrane protein2,PRRT2)基因與發(fā)作性運(yùn)動(dòng)誘發(fā)性運(yùn)動(dòng)障礙相關(guān),為PKD的致病基因,這使得我們對(duì)PKD有了突破性的認(rèn)識(shí)。PRRT2基因作為PKD的致病基因被發(fā)現(xiàn),可以為此類疾病分子水平診斷提供新的經(jīng)驗(yàn)和證據(jù),能夠提高患者的確診率,而對(duì)于患者的下一代,產(chǎn)前基因檢測(cè)可很好的預(yù)防基因傳遞。目的對(duì)一個(gè)家族性發(fā)作性運(yùn)動(dòng)誘發(fā)性運(yùn)動(dòng)障礙家系進(jìn)行臨床表型研究,從而對(duì)該疾病有更深層次的認(rèn)識(shí),并對(duì)該家系進(jìn)行基因檢測(cè),以期獲得新的突變位點(diǎn),為此類疾病分子水平診斷提供新的經(jīng)驗(yàn)和證據(jù),并探討PKD的發(fā)病機(jī)制。方法1.收集資料本研究收集了在鄭州大學(xué)第一附屬醫(yī)院神經(jīng)內(nèi)科臨床診斷為發(fā)作性運(yùn)動(dòng)誘發(fā)性運(yùn)動(dòng)障礙的患者及其家族成員的臨床資料,對(duì)患者的臨床癥狀進(jìn)行分析,并在取得患者及家屬同意的基礎(chǔ)上,經(jīng)鄭州大學(xué)第一附屬醫(yī)院的倫理委員會(huì)批準(zhǔn)后,抽取患者及家屬外周血行基因檢測(cè)分析。2.基因組DNA提取采用相關(guān)液相捕獲試劑盒提取基因組DNA。3.樣品文庫(kù)的制備,然后行文庫(kù)的質(zhì)量檢測(cè),目標(biāo)區(qū)域捕獲實(shí)驗(yàn)。4.基因突變分析捕獲序列在測(cè)序儀上進(jìn)行高通量測(cè)序,隨后數(shù)據(jù)分析。結(jié)果1.該家系連續(xù)3代發(fā)病,Ⅰ_1、Ⅱ_3、Ⅱ_6、Ⅲ_4、Ⅲ_6發(fā)病年齡分別為26、17、16、12、10歲,每代發(fā)病年齡逐漸提前,病情加重。2.5位患者存在類似的誘發(fā)因素及表現(xiàn),為突然運(yùn)動(dòng)后誘發(fā)的四肢肌張力障礙,但在同一家系中的患者之間存在不同的臨床表型:Ⅰ1發(fā)作時(shí)伴有言語(yǔ)不能或發(fā)音不清的表現(xiàn);Ⅱ6情緒激動(dòng)或緊張時(shí)也可誘發(fā),并伴有痙攣性斜頸的癥狀;并;Ⅲ6在體位變化時(shí)同樣可出現(xiàn)癥狀。3.Ⅱ3、Ⅱ6、Ⅲ4、Ⅲ6外周血基因測(cè)序分析后得出結(jié)果:PRRT2基因雜合缺失。4.服用小劑量抗癲癇藥物如卡馬西平、苯妥英鈉的發(fā)作性運(yùn)動(dòng)誘發(fā)性運(yùn)動(dòng)障礙的患者,癥狀均能得到很好的控制。結(jié)論1.家族性發(fā)作性運(yùn)動(dòng)誘發(fā)性運(yùn)動(dòng)障礙家系存在遺傳早現(xiàn)現(xiàn)象,且此疾病存在臨床表型異質(zhì)性或外顯不全的可能性。2.PRRT2基因是家族性發(fā)作性運(yùn)動(dòng)誘發(fā)性運(yùn)動(dòng)障礙的致病基因,PRRT2基因的雜合缺失可導(dǎo)致家族性發(fā)作性運(yùn)動(dòng)誘發(fā)性運(yùn)動(dòng)障礙。3對(duì)于臨床癥狀提示發(fā)作性運(yùn)動(dòng)誘發(fā)性運(yùn)動(dòng)障礙的患者,在排除了癲癇等相似疾病以及繼發(fā)性發(fā)作性運(yùn)動(dòng)誘發(fā)性運(yùn)動(dòng)障礙的可能性后,可行基因檢測(cè)以明確診斷。
[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，
本文編號(hào)：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，
本文編號(hào)：2282850
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