Genetic testing for Parkinson's disease in clinical practice

Abstract

The identification of disease-causing mutations or strong risk factors for Parkinson's disease in genes encoding proteins such as α-synuclein (SNCA), leucine-rich repeat kinase-2 (LRRK2), or glucocerebrosidase (GBA1) has led to a better understanding of the different components of disease pathogenesis. Many gene and mutation-specific targeted disease-modifying treatments are under development and several studies are under way. It is, therefore, important to raise awareness among patients and their families and to offer genetic testing, at least to those patients who are considering to participate in innovative trials.

Keywords: Disease mechanisms; Gene mutations; Glucocerebrosidase; LRRK2; Parkinson’s disease; Synuclein.

Fig. 1

Genetic architecture of Parkinson’s disease (PD). Rare mutations in several genes confer a high or very high risk to develop the disease, they can be considered as “causative”, while a large number of common risk variants have a small, but measurable effect on disease risk. Some variants with intermediate frequency, for example the LRRK2 G2019S variant or variants in the GBA1 gene are strong “driver” risk variants of moderate effect strengths. Modified from Manolio et al. (2009)