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

Area of Science:

• Neurogenetics
• Genomic Medicine

Background:

• Parkinson's disease (PD) has a significant genetic basis, with an increasing number of associated genes and variations identified.
• Establishing genotype-phenotype correlations is crucial for understanding PD inheritance and prognosis.
• Existing literature and ongoing research continuously expand the genetic landscape of PD.

Purpose of the Study:

• To identify genetic variants associated with Parkinson's disease using targeted gene panel next-generation sequencing (NGS).
• To explore the utility of re-analyzing variants of unknown significance (VUS) over time.
• To enhance the clinical and genetic understanding of Parkinson's disease.

Main Methods:

• Targeted gene panel next-generation sequencing (NGS) was employed to screen 18 known PD-related genes in 43 patients.
• Genetic variants were analyzed in patients attending an outpatient clinic between 2018-2019.
• Detected variants, including those classified as VUS, were re-evaluated after a 12-24 month interval.

Main Results:

• Fourteen distinct heterozygous variants were identified in 14 individuals from nonconsanguineous families.
• These variants were classified as pathogenic, likely pathogenic, or VUS.
• Re-analysis of 15 variants led to changes in their interpretation, demonstrating the dynamic nature of variant classification.

Conclusions:

• Targeted gene panel NGS is effective for confident identification of genetic variants linked to Parkinson's disease.
• Periodic re-analysis of genetic variants, particularly VUS, can refine diagnoses and improve clinical management.
• This study underscores the importance of dynamic genetic assessment in the evolving understanding of PD.