Genome sequencing in the Parkinson’s disease clinic

Abstract

Background and ObjectivesGenetic variants impact both Parkinson’s disease (PD) risk and manifestations. While genetic information is of potential interest to patients and clinicians, genetic testing is rarely performed during routine PD clinical care. The goal of this study was to perform genome sequencing and examine patient interest in comprehensive genetic testing for PD in 2 academic movement disorder clinics.MethodsIn 208 subjects with PD (age=63 years, 67% male), genome sequencing was performed and filtered using a custom panel, including 49 genes associated with PD, parkinsonism, or related disorders, as well as a 90-variant PD genetic risk score. Separately, 231 patients (age=67 years, 63% male) were surveyed on interest in genetic testing at baseline and in response to vignettes covering (i) familial risk of PD (LRRK2); (ii) risk of PD dementia (GBA); (iii) PD genetic risk score; and (iv) secondary, medically-actionable variants (BRCA1).ResultsGenome sequencing revealed a LRRK2 variant in 3.4% and a GBA risk variant in 10.1% of our clinical sample. The genetic risk score was normally distributed, identifying 42 subjects with high risk of PD. Medically-actionable findings were discovered in 2 subjects (1%). In our survey, the majority (82%) responded they would share a LRRK2 variant with relatives. Most registered unchanged or increased interest in testing when confronted with potential risk for dementia or medically- actionable findings, and most (75%) expressed interest in learning their PD genetic risk score.DiscussionOur results highlight broad interest in comprehensive genetic testing among patients with PD and may facilitate integration of genome sequencing in clinical practice.

GiOPARK Project: The Genetic Study of Parkinson’s Disease in the Croatian Population

“…In a Central Asian study of an early-onset Parkinson's disease population in Kazakhstan, pathogenic mutations were found in only 6% of cases and only in the LRRK2 and PRKN genes, confirming regional differences between populations [46]. Another study on a heterogeneous population of 203 patients and all types of presentation showed a high yield of pathological variants of 20.19%, mainly in the GBA (10%) and LRRK2 (3%) genes [47]. Slightly lower but significant percentages were found in American patients of European origin, where the percentage of GBA variants was 7.1%, and SNCA, LRRK2, and PRKN variants were 2% [48].…”