Westenberger Ana, Brüggemann Norbert, Klein Christine
Institute of Neurogenetics, University of Lübeck and University Hospital Schleswig-Holstein, Campus Lübeck, 23538 Lübeck, Germany
Department of Neurology, University of Lübeck and University Hospital Schleswig-Holstein, Campus Lübeck, 23538 Lübeck, Germany.
Cold Spring Harb Perspect Med. 2024 Aug 12. doi: 10.1101/cshperspect.a041774.
The genetic architecture of Parkinson's disease (PD) comprises five autosomal dominantly inherited forms with a clinical picture overall resembling idiopathic disease (PARK-, PARK-, PARK-, PARK-, and PARK-) and three recessive types (PARK-, PARK-, and PARK-), several monogenic forms causing atypical parkinsonism, as well as a plethora of known genetic risk factors, most notably and including a recently discovered risk variant unique to individuals of African descent, as well as polygenic scores. The Movement Disorder Society Genetic mutation database (MDSGene) (www.mdsgene.org) provides PD genotype-phenotype relationships, whereas global PD genetics networks, such as the Global Parkinson's Genetics Program (www.gp2.org) elucidate PD genetic factors at an unprecedented scale. Two large studies in relatively unselected, multicenter PD samples estimate the frequency of genetic forms, including PARK-, at ∼15%. PD genetics are becoming increasingly actionable, with the first gene-targeted clinical trials underway. Furthermore, PD genetics has recently been incorporated into a new biological classification of PD.
帕金森病（PD）的遗传结构包括五种常染色体显性遗传形式，其临床表现总体上类似于特发性疾病（PARK - 、PARK - 、PARK - 、PARK - 和PARK - ）以及三种隐性类型（PARK - 、PARK - 和PARK - ），还有几种导致非典型帕金森症的单基因形式，以及大量已知的遗传风险因素，最显著的是 以及 ，包括最近发现的非洲裔个体特有的风险变异，还有多基因评分。运动障碍协会基因突变数据库（MDSGene）（www.mdsgene.org）提供了PD的基因型 - 表型关系，而全球PD遗传学网络，如全球帕金森病遗传学项目（www.gp2.org）以前所未有的规模阐明了PD的遗传因素。在相对未经过选择的多中心PD样本中进行的两项大型研究估计，包括PARK - 在内的遗传形式的频率约为15%。随着首个针对基因的临床试验正在进行，PD遗传学正变得越来越具有可操作性。此外，PD遗传学最近已被纳入PD的一种新的生物学分类中。
