Determining the genetic aetiology of early onset Parkinson's disease

帕金森吗?帕金森氏病（PD）是一种常见的退行性脑部疾病，患者神经细胞的丧失会导致行动迟缓、震颤、僵硬和行走困难。随着病情的发展，一些患者会发展为痴呆，并逐渐丧失行为能力。目前还没有治疗方法可以逆转对大脑的损害或阻止疾病的发展。一些年轻PD患者有常染色体隐性遗传病。我们都携带大约2万个基因的两个副本。在常染色体隐性遗传病中，一个基因的两个错误拷贝会导致基因功能的丧失。在这种形式的基因遗传中，儿童或受影响患者的父母通常不会增加患病风险。迄今为止，已经确定了三种常染色体隐性帕金森病的基因，这对于导致新的帕金森病基因检测和帮助我们了解疾病过程非常重要。我们怀疑帕金森病是一种异质性疾病，有许多不同的过程导致类似的临床综合征。这项工作的主要目标将是确定新的疾病基因，这将使对这种疾病进行更准确的基因检测，适当地针对正确的患者进行新的治疗，并在细胞和动物模型中开发新的治疗方法。在我们的工作中，我们已经表明，在早发性PD患者中，有强有力的证据表明存在更多的常染色体隐性基因，我们已经确定了一组71例早发性PD患者（EOPD），他们可能有这种类型的基因改变，导致PD。我们将使用最近开发的称为下一代测序的技术，通过对这71名患者的详细研究，确定导致PD的新基因。这可以快速扫描人类基因组中所有20,000个基因的基因变化。这将识别出一系列可能的新基因。第二阶段将试图在1300名EOPD患者中证实这些发现。帕金森病新基因的鉴定将带来新的诊断测试，更好地了解各种形式的帕金森病，并开发新的细胞和动物模型。这将允许开发新的治疗方法，我们希望这将改善PD患者的前景。

Parkinson?s disease (PD) is a common degenerative brain disease in which loss of nerve cells leads to slowness of movement, tremor, stiffness and difficulty walking. As the disease progresses some patients develop dementia and become increasingly incapacitated. There are no treatments that reverse the damage to the brain or halt the disease process. Some younger patients with PD have autosomal recessive genetic disease. We all carry two copies of about 20,000 genes. In autosomal recessive disease two faulty copies of a gene lead to loss of gene function. In this form of genetic inheritance there is usually no increased risk of disease for children or parents of affected patients. To date three genes have been identified for autosomal recessive PD which have been important in leading to new genetic tests for PD, and in helping us to understand the disease processes. We suspect that PD is a heterogeneous disease, with many different processes leading to a similar clinical syndrome. The main goal of this work will be to identify new disease genes which will enable more accurate genetic testing for this condition, the appropriate targeting of new treatments to the correct patients and the development of new treatments in cell and animal models. In our work we have shown that among early onset PD patients there is strong evidence for the existence of further autosomal recessive genes and we have identified a set of 71 early onset PD patients (EOPD) who are likely to have this type of gene change, causing PD. We will identify new genes that cause PD by detailed study of these 71 patients using a recently developed technique called next generation sequencing. This allows a rapid scan for gene changes across all 20,000 genes in the human genome. This will identify a series of possible new genes. The second stage will be to try to confirm these findings in a large representative set of 1300 EOPD patients. The identification of new genes for PD will lead to new diagnostic tests, a better understanding of various forms of PD and the development of new cell and animal models for the disease. This will allow the development of new treatments that we hope will improve the outlook for people with PD.