Determining the genetic aetiology of early onset Parkinson's disease

帕金森-S病(PD)是一种常见的退行性脑部疾病，神经细胞丢失导致运动迟缓、震颤、僵硬和行走困难。随着疾病的发展，一些患者会患上痴呆症，并变得越来越丧失能力。没有任何治疗方法可以逆转对大脑的损害或阻止疾病的进程。一些年轻的帕金森病患者有常染色体隐性遗传病。我们每个人都携带大约20,000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丧失。在这种形式的遗传中，儿童或受影响患者的父母通常不会增加患病风险。到目前为止，已发现三个常染色体隐性遗传性帕金森病基因，这些基因对帕金森病新的基因测试和帮助我们了解疾病过程具有重要意义。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是识别新的疾病基因，从而能够对这种疾病进行更准确的基因测试，针对正确的患者进行适当的新治疗，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，我们发现在早发性帕金森病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71例早发性帕金森病患者(EOPD)，他们可能具有这种类型的基因变化，导致帕金森病。我们将通过对这71名患者的详细研究，使用一种名为下一代测序的技术来识别导致帕金森病的新基因。这使得快速扫描人类基因组中所有20,000个基因的基因变化成为可能。这将确定一系列可能的新基因。第二阶段将试图在1300名具有代表性的EOPD患者中证实这些发现。帕金森病新基因的识别将导致新的诊断试验，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来治疗该病。这将允许开发新的治疗方法，我们希望这些治疗方法将改善帕金森病患者的前景。

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.