Lill C M, Klein C
Institut für Neurogenetik, Universitätsklinikum Schleswig Holstein, Campus Lübeck, Universität zu Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Deutschland.
Nervenarzt. 2017 Apr;88(4):345-355. doi: 10.1007/s00115-017-0288-0.
Parkinson's disease (PD) is the second most common neurodegenerative disease and has a growing socioeconomic impact due to demographic changes in the industrial nations. There are several forms of PD, a fraction of which (<5%) are monogenic, i. e. caused by mutations in single genes. At present, six genes have been established for the clinically classical form of parkinsonism including three autosomal dominantly (SNCA, LRRK2, VPS35) and three autosomal recessively inherited ones (Parkin, PINK1, DJ-1). In addition, there are a plethora of genes causing atypical forms of parkinsonism. In contrast, idiopathic PD is of a multifactorial nature. Genome-wide association studies have established a total of 26 genetic loci for this form of the disease; however, for most of these loci the underlying functional genetic variants have not yet been identified and the respective disease mechanisms remain unresolved. Furthermore, there are a number of environmental and life style factors that are associated with idiopathic PD. Exposure to pesticides and possibly a history of head trauma represent genuine risk factors. Other PD-associated factors, such as smoking and intake of coffee and alcohol may not represent risk factors per se and the cause-effect relationship has not yet been elucidated for most of these factors. A patient with a positive family history and/or an early age of disease onset should undergo counseling with respect to a possible monogenic form of the disease. Disease prediction based on genetic, environmental and life style factors is not yet possible for idiopathic PD and potential gene-specific therapies are currently in the development or early testing phase.
帕金森病(PD)是第二常见的神经退行性疾病,由于工业化国家的人口结构变化,其对社会经济的影响日益增大。帕金森病有多种形式,其中一小部分(<5%)是单基因性的,即由单个基因突变引起。目前,已确定了六种与临床经典帕金森症形式相关的基因,包括三种常染色体显性遗传基因(SNCA、LRRK2、VPS35)和三种常染色体隐性遗传基因(Parkin、PINK1、DJ-1)。此外,还有大量基因可导致非典型帕金森症形式。相比之下,特发性帕金森病具有多因素性质。全基因组关联研究已确定了这种疾病形式的总共26个基因位点;然而,对于这些位点中的大多数,尚未确定潜在的功能性遗传变异,相应的疾病机制仍未得到解决。此外,有许多环境和生活方式因素与特发性帕金森病相关。接触杀虫剂以及可能的头部外伤史是真正的风险因素。其他与帕金森病相关的因素,如吸烟、咖啡和酒精摄入,本身可能并非风险因素,而且对于这些因素中的大多数,因果关系尚未阐明。有阳性家族史和/或疾病发病年龄较早的患者应就可能的单基因疾病形式接受咨询。对于特发性帕金森病,基于遗传、环境和生活方式因素的疾病预测目前尚不可能,潜在的基因特异性疗法目前正处于开发或早期测试阶段。