帕金森病和帕金森综合征基因发现的临床意义。
Clinical implications of gene discovery in Parkinson's disease and parkinsonism.
机构信息
Department of Neurology, Mayo Clinic, Jacksonville, Florida 32224, USA.
出版信息
Mov Disord. 2010;25 Suppl 1:S15-20. doi: 10.1002/mds.22723.
Over the past decade, major progress has been achieved in the identification of genes associated with Parkinson's disease (PD) and parkinsonism. Five genes have now been shown conclusively to play a role in PD susceptibility. Mutations in three of these genes, PRKN, PINK1, and DJ1, are important in early onset, recessively inherited PD, while mutations in LRRK2 and SNCA result in autosomal-dominant PD. LRRK2 has emerged as the most prevalent genetic cause of PD and has been implicated in both familial and sporadic forms of disease. In addition, autosomal-dominant dementia and Parkinsonism has been shown to be caused by mutations in the MAPT and PGRN genes. Molecular tests are now commercially available for several of these genes; however, in some of them, positive results need to be interpreted with caution until penetrance is better understood. In addition, clinical treatment of PD remains largely unaltered by the results of genetic testing.
在过去的十年中,与帕金森病(PD)和帕金森综合征相关的基因鉴定取得了重大进展。现在已经明确了五个基因在 PD 易感性中发挥作用。这三个基因中的突变,即 PRKN、PINK1 和 DJ1,在早发性、隐性遗传 PD 中很重要,而 LRRK2 和 SNCA 的突变导致常染色体显性 PD。LRRK2 已成为 PD 最常见的遗传原因,并与家族性和散发性疾病有关。此外,已经表明,MAPT 和 PGRN 基因突变会导致常染色体显性痴呆和帕金森综合征。现在已经有几种这些基因的分子检测可供商业使用;然而,在其中一些基因中,阳性结果需要谨慎解释,直到更好地了解外显率。此外,基因检测结果对 PD 的临床治疗并没有太大改变。