Department of Neurology, National Neuroscience Institute, Singapore.
Parkinsonism Relat Disord. 2014 Jan;20 Suppl 1:S54-6. doi: 10.1016/S1353-8020(13)70015-4.
Genetic testing has played an important role for the diagnosis of many rare monogenic disorders. However, the role and limitations of genetic testing have generated considerable debate in the medical community. In recent years, the identification of several monogenic genes in Parkinson's disease (PD), a common neurodegenerative disorder, has led to calls for genetic testing guidelines for this disorder. Genetic testing of LRRK2 provides an excellent platform to highlight some of the pertinent issues (generic and specific) related to genetic testing in PD. The identification of a common recurrent mutation (G2019S) worldwide provides an opportunity for developing guidelines that are applicable internationally. However, the incomplete penetrance of the mutation and the lack of clarity of the pathogenicity of many other reported LRRK2 mutations call for cautious implementation of genetic testing programs. The clinical utility of genetic testing is compounded by easy accessibility of Direct to Consumer genetic services and the relative lack of regulation on reliability of service providers in internet advertisements. Based on current literature, genetic testing of LRRK2 (particularly for G2019S) certainly has a clinical role, though it is applicable primarily in select scenarios and in certain at-risk populations.
遗传检测在许多罕见的单基因疾病的诊断中发挥了重要作用。然而，遗传检测的作用和局限性在医学界引起了相当大的争议。近年来，在常见的神经退行性疾病帕金森病（PD）中，几个单基因的鉴定导致了针对这种疾病的遗传检测指南的呼吁。LRRK2 的基因检测为突出与 PD 遗传检测相关的一些（通用和特定）问题提供了一个极好的平台。在全球范围内发现一种常见的反复突变（G2019S）为制定国际适用的指南提供了机会。然而，该突变的不完全外显率和许多其他报道的 LRRK2 突变的致病性不明确，要求谨慎实施遗传检测计划。由于直接面向消费者的基因服务的便捷获取以及互联网广告中对服务提供商可靠性的监管相对缺乏，遗传检测的临床实用性更加复杂。根据目前的文献，LRRK2 的基因检测（特别是针对 G2019S）肯定具有临床作用，尽管它主要适用于某些特定的情况和某些高危人群。
