The discovery of LRRK2 mutations as a cause of Parkinson's disease (PD), including the sporadic late-onset form, established the decisive role of genetics in the field of PD research. Among LRRK2 mutations, the G2019S, mostly lying in a haplotype originating from a common Middle Eastern ancestor, has been identified in different populations worldwide. The G2385R and R1628P variants represent validated risk factors for PD in Asian populations. Here, we describe in detail the origin, the present worldwide epidemiology, and the penetrance of LRRK2 mutations. Furthermore, this chapter aims to characterize other definitely/probably pathogenic mutations and risk variants of LRRK2. Finally, we provide some general guidelines for a LRRK2 genetic testing and counseling. In summary, LRRK2 discovery revolutionized the understanding of PD etiology and laid the foundation for a promising future of genetics in PD research.
Keywords: Dardarin; Familial Parkinson’s disease; LRRK2; LRRK2 mutations; Leucine-rich repeat kinase 2; PARK8; Parkinson’s disease; Parkinson’s disease genetics.