Re-evaluation of Genetic Variants in Parkinson's Disease Using Targeted Panel and Next-Generation Sequencing

KABLAN A., SILAN F., Ozdemir O.

Twin research and human genetics : the official journal of the International Society for Twin Studies, vol.26, no.2, pp.164-170, 2023 (SCI-Expanded) identifier identifier


Parkinson's disease (PD) is a complex disorder with a significant genetic component. Genetic variations associated with PD play a crucial role in the disease's inheritance and prognosis. Currently, 31 genes have been linked to PD in the OMIM database, and the number of genes and genetic variations identified is steadily increasing. To establish a robust correlation between phenotype and genotype, it is essential to compare research findings with existing literature. In this study, we aimed to identify genetic variants associated with PD using a targeted gene panel with next-generation sequencing (NGS) technology. Our objective was also to explore the idea of re-analyzing genetic variants of unknown significance (VUS). We screened 18 genes known to be related to PD using NGS in 43 patients who visited our outpatient clinic between 2018-2019. After 12-24 months, we re-evaluated the detected variants. We found 14 different heterozygous variants classified as pathogenic, likely pathogenic, or VUS in 14 individuals from nonconsanguineous families. We re-evaluated 15 variants and found changes in their interpretation. Targeted gene panel analysis with NGS can help identify genetic variants associated with PD with confidence. Re-analyzing certain variants at specific time intervals can be especially beneficial in selected situations. Our study aims to expand the clinical and genetic understanding of PD and emphasizes the importance of re-analysis.