Aasly Jan O
Department of Neurology, St. Olav's Hospital, Trondheim, Norway.
Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.
J Mov Disord. 2020 May;13(2):81-96. doi: 10.14802/jmd.19080. Epub 2020 May 29.
Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects 1-2% of people by the age of 70 years. Age is the most important risk factor, and most cases are sporadic without any known environmental or genetic causes. Since the late 1990s, mutations in the genes SNCA, PRKN, LRRK2, PINK1, DJ-1, VPS35, and GBA have been shown to be important risk factors for PD. In addition, common variants with small effect sizes are now recognized to modulate the risk for PD. Most studies in genetic PD have focused on finding new genes, but few have studied the long-term outcome of patients with the specific genetic PD forms. Patients with known genetic PD have now been followed for more than 20 years, and we see that they may have distinct and different prognoses. New therapeutic possibilities are emerging based on the genetic cause underlying the disease. Future medication may be based on the pathophysiology individualized to the patient's genetic background. The challenge is to find the biological consequences of different genetic variants. In this review, the clinical patterns and long-term prognoses of the most common genetic PD variants are presented.
帕金森病（PD）是一种进行性神经退行性疾病，在70岁人群中的发病率为1%-2%。年龄是最重要的风险因素，大多数病例为散发性，无任何已知的环境或遗传病因。自20世纪90年代末以来，已证明基因SNCA、PRKN、LRRK2、PINK1、DJ-1、VPS35和GBA中的突变是帕金森病的重要风险因素。此外，现在认识到效应大小较小的常见变异可调节帕金森病的风险。大多数遗传性帕金森病研究都集中在寻找新基因上，但很少有研究关注特定遗传性帕金森病形式患者的长期预后。已知患有遗传性帕金森病的患者现已被随访超过20年，我们发现他们可能有不同的预后。基于该疾病潜在的遗传病因，新的治疗可能性正在出现。未来的药物治疗可能基于针对患者遗传背景个体化的病理生理学。挑战在于找出不同基因变异的生物学后果。在本综述中，介绍了最常见遗传性帕金森病变异的临床模式和长期预后。
