2011年11月26日,，中南大學(xué)湘雅醫(yī)院在神經(jīng)病學(xué)領(lǐng)域國(guó)際權(quán)威雜志Brain期刊網(wǎng)站上率先發(fā)表了他們最新研究成果"Identification of PRRT2 as the causative gene of paroxysmal kinesigenic dyskinesias",，在這項(xiàng)研究中他們與合作者在國(guó)際上首次發(fā)現(xiàn)和克隆了“舞蹈手足徐動(dòng)癥”的第一個(gè)致病基因PRRT2。
12歲的學(xué)生李敏(化名)最近被老師和同學(xué)指責(zé)上課搞“惡作劇”：回答問(wèn)題時(shí)雙手不自主的“舞蹈”,，或“擠眉弄眼”地搞怪,。他還時(shí)而感覺(jué)到雙腳僵硬經(jīng)常摔倒，幾次險(xiǎn)些出了車禍,。
經(jīng)查明,，李敏患有發(fā)作性運(yùn)動(dòng)誘發(fā)性運(yùn)動(dòng)障礙(PKD)，又稱發(fā)作性運(yùn)動(dòng)誘發(fā)的舞蹈手足徐動(dòng)癥,。這一類以發(fā)作性肢體不自主運(yùn)動(dòng)和軀體姿態(tài)異常的發(fā)生與遺傳因素有關(guān),。李敏家族中的父親,、叔叔、奶奶等四代人,、超10人均患上了這個(gè)怪病,。另有醫(yī)學(xué)專家認(rèn)為腦血管病、代謝紊亂,、腦外傷等也可能誘發(fā)此病,。
湘雅醫(yī)院神經(jīng)內(nèi)科唐北沙教授領(lǐng)銜的團(tuán)隊(duì)與上海交通大學(xué)醫(yī)學(xué)院附屬瑞金醫(yī)院神經(jīng)內(nèi)科、中山大學(xué)附屬第一醫(yī)院神經(jīng)內(nèi)科,、中南大學(xué)醫(yī)學(xué)遺傳學(xué)國(guó)家重點(diǎn)實(shí)驗(yàn)室,、深圳華大基因科技有限公司等多家單位合作，通過(guò)對(duì)PKD深入研究,，發(fā)現(xiàn)在人腦高表達(dá)的PRRT2(富脯氨酸跨膜蛋白2)基因突變后,，可導(dǎo)致該病發(fā)生，并在國(guó)際上首次研究發(fā)現(xiàn)PRRT2基因是PKD的第一個(gè)致病基因,。
參與研究的王俊嶺博士說(shuō),，PKD已有較多的病例報(bào)道，目前定位了2個(gè)致病基因區(qū)間,，但至今未能克隆出致病基因,。（生物谷Bioon.com）
doi:10.1093/brain/awr289
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PMID:
Identification of PRRT2 as the causative gene of paroxysmal kinesigenic dyskinesias
Jun-Ling Wang1,*, Li Cao2,*, Xun-Hua Li3,*, Zheng-Mao Hu4, Jia-Da Li4, Jian-Guo Zhang5, Yu Liang5, San-A5, Nan Li1, Su-Qin Chen6, Ji-Feng Guo1,7, Hong Jiang1,7, Lu Shen1,7, Lan Zheng2, Xiao Mao1, Wei-Qian Yan1, Ying Zhou1, Yu-Ting Shi1, San-Xi Ai1, Mei-Zhi Dai5, Peng Zhang5, Kun Xia4, Sheng-Di Chen2 and Bei-Sha Tang1,4,7
Paroxysmal kinesigenic dyskinesias is a paroxysmal movement disorder characterized by recurrent, brief attacks of abnormal involuntary movements induced by sudden voluntary movements. Although several loci, including the pericentromeric region of chromosome 16, have been linked to paroxysmal kinesigenic dyskinesias, the causative gene has not yet been identified. Here, we identified proline-rich transmembrane protein 2 (PRRT2) as a causative gene of paroxysmal kinesigenic dyskinesias by using a combination of exome sequencing and linkage analysis. Genetic linkage mapping with 11 markers that encompassed the pericentromeric of chromosome 16 was performed in 27 members of two families with autosomal dominant paroxysmal kinesigenic dyskinesias. Then, the whole-exome sequencing was performed in three patients from these two families. By combining the defined linkage region (16p12.1–q12.1) and the results of exome sequencing, we identified an insertion mutation c.649_650InsC (p.P217fsX7) in one family and a nonsense mutation c.487C>T (p.Q163X) in another family. To confirm our findings, we sequenced the exons and flanking introns of PRRT2 in another three families with paroxysmal kinesigenic dyskinesias. The c.649_650InsC (p.P217fsX7) mutation was identified in two of these families, whereas a missense mutation, c.796C>T (R266W), was identified in another family with paroxysmal kinesigenic dyskinesias. All of these mutations completely co-segregated with the phenotype in each family. None of these mutations was identified in 500 normal unaffected individuals of matched geographical ancestry. Thus, we have identified PRRT2 as the first causative gene of paroxysmal kinesigenic dyskinesias, warranting further investigations to understand the pathogenesis of this disorder.
