Genetic testing of LRRK2 in Parkinson's disease: is there a clinical role?

Abstract

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.