原发性震颤的遗传机制研究

Essential tremor (ET), the cause of which remains poorly understood, is one of the most common movement disorders.The main characteristics of ET is the slow progressive postural tremor or action tremor of bilateral upper limbs. 50% to 70% of the patients with ET have a positive family history, and it is an autosomal dominant disorder with incomplete penetrance. The prevalence of ET worldwide ranges probably from 0.4% to 5% by general estimation. Cytogenetic examination revealed that sex chromosomes were associated with ET. Linkage analysis of ET families identified three disease loci, which located in chromosome 3q13 (ETM1), 2p22-25 (ETM2) and 6p23(ETM3). Given that ET has a strong genetic heterogeneity and there may be exist other locus, and the main disease genes or susceptibility genes have not been identified and separated, it seriously hindered the understanding of the pathogenetic mechanism of the disease and the development of clinical gene diagnostic method. This study will use a combined strategy of microsatellite polymorphism genome-wide scan and exome sequencing to narrow the current site interval or identified a novel ET locus, and isolate an ET disease gene, elucidate the genetic basis of ET.

原发性震颤（essential tremor, ET）是一种常见的原因不明的运动疾病，主要特征为缓慢进展的双侧上肢姿势性或动作性震颤。50％-70％的ET患者有阳性家族史，主要呈常染色体显性遗传，外显不完全，一般估计ET患病率为0.4%-5%。细胞遗传学检测显示性染色体与ET相关，对家系连锁分析也定位了3个位点，分别位于染色体3q13（ETM1）、2p22-25（ETM2）和6p23(ETM3)。由于ET有较强的遗传异质性，可能存在其它的致病基因位点，主要的致病基因或易感基因并未被鉴定，严重阻碍了对该疾患的病理遗传学机制的认识和临床基因诊断的开展。本研究拟采用微卫星多态全基因组扫描定位和外显子组测序相结合的策略，缩小目前定位的ET位点区间或定位新的ET位点、鉴定ET致病基因，阐明原发性震颤的遗传学基础。

原发性震颤（essential tremor, ET）是一种常见的原因不明的运动疾病，主要特征为缓慢进展的双侧上肢姿势性或动作性震颤。50％-70％的ET患者有阳性家族史，主要呈常染色体显性遗传，外显不完全，一般估计ET患病率为0.4%-5%。细胞遗传学检测显示性染色体与ET相关，对家系连锁分析也定位了3个位点，分别位于染色体3q13（ETM1）、2p22-25（ETM2）和6p23(ETM3)。由于ET有较强的遗传异质性，可能存在其它的致病基因位点，主要的致病基因或易感基因并未被鉴定，严重阻碍了对该疾患的病理遗传学机制的认识和临床基因诊断的开展。本研究通过对多个家系的外显子组测序，以及病例对照研究，定位了3个新的ET位点并鉴定ET致病基因，有助于阐明原发性震颤的遗传学基础。

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