Section of Clinical and Molecular Neurogenetics, Department of Neurology, University of Lübeck, Lübeck, Germany.
Curr Opin Neurol. 2012 Aug;25(4):466-74. doi: 10.1097/WCO.0b013e3283547627.
We will review the recent advances in the genetics of Parkinson disease and other movement disorders such as dystonia, essential tremor and restless legs syndrome (RLS).
Mutations in VPS35 were identified as a novel cause of autosomal dominant Parkinson disease using exome sequencing. Next generation sequencing (NGS) was also used to identify PRRT2 mutations as a cause of paroxysmal kinesigenic dyskinesia (DYT10). Using a different technique, that is linkage analysis, mutations in EIF4G1 were implicated as a cause of Parkinson disease and mutations in SLC20A2 as a cause of familial idiopathic basal ganglia calcification. Furthermore, genome-wide association studies (GWAS) and meta-analyses have confirmed known risk genes and identified new risk loci in Parkinson disease, RLS and essential tremor. New models to study genetic forms of Parkinson disease, such as stem cell-derived neurons, have helped to elucidate disease-relevant molecular pathways, such as the molecular link between Gaucher disease and Parkinson disease.
New genes have been implicated in Parkinson disease and other movement disorders through the use of NGS. The identification of risk variants has been facilitated by GWAS and meta-analyses. Furthermore, new models are being developed to study the molecular mechanisms involved in the pathogenesis of these diseases.
我们将回顾帕金森病和其他运动障碍（如肌张力障碍、特发性震颤和不宁腿综合征）遗传学的最新进展。
使用外显子组测序发现 VPS35 突变是常染色体显性遗传帕金森病的新病因。下一代测序（NGS）也被用于确定 PRRT2 突变是阵发性运动诱发运动障碍（DYT10）的病因。使用不同的技术，即连锁分析，发现 EIF4G1 突变是帕金森病的病因，SLC20A2 突变是家族性特发性基底节钙化的病因。此外，全基因组关联研究（GWAS）和荟萃分析证实了已知的风险基因，并在帕金森病、不宁腿综合征和特发性震颤中确定了新的风险位点。研究遗传形式帕金森病的新模型，如干细胞衍生神经元，有助于阐明与疾病相关的分子途径，如 Gaucher 病和帕金森病之间的分子联系。
通过使用 NGS，新的基因被牵连到帕金森病和其他运动障碍中。GWAS 和荟萃分析促进了风险变异的鉴定。此外，正在开发新的模型来研究这些疾病发病机制中涉及的分子机制。
