Objective: Parkinson’s disease (PD) is a neurodegenerative disorder that affects millions of people. There is growing evidence on both gene mutations associated with PD and genetic factors contributing to PD risk. The object of this study is to design, validate, and implement a clinical comprehensive NextGen (NGS) gene panel for PD diagnosis.

Background: The number of known monogenic causal genes for PD has increased significantly, similarly to susceptibility genes. The advancement of NGS technology opened the avenue for efficient genetic testing. However, most genetic PD tests focus on classic PD genes and often consider a positive family history before testing. To bring up-to-date genetics to PD clinician’s toolbox, we developed a 94-gene Parkinson Disease Panel to evaluate both inherited and sporadic forms of PD as a comprehensive clinical test.

Method: A multidisciplinary team of experts in Mayo Clinic Neurology, Genetics, and Laboratory Medicine and Pathology collaborated to develop this PD gene panel. We identified genes associated with PD based on primary literature, clinical guideline, and expert input. Upon expert consensus, 94 genes were included for clinical testing, doubling the gene counts over most existing tests. Both public and private mutation databases, with >100,000 entries, were considered for technical evaluation by NGS method. We also evaluated challenging mutations and common disease-causing mutations, some of which have higher frequency in certain populations.

Technical performance of this 94 gene Parkinson Disease Panel is validated to detect 95% of deletions up to 75base pairs (bp) and insertions up to 47bp (including certain mobile element), and high-resolution copy number analysis to single and multi-exon events. All detected variants are reported according to American College of Medical Genetics and Genomics (ACMG) recommendations.

Results: Overall, the launch of a 94 gene Parkinson Disease Panel represents a significant step towards personalized medicine for PD patients. With streamlined laboratory workflows and optimized clinical turnaround time, this test showed initial success in PD evaluation.

Conclusion: Incorporating gene panels into PD management will improve patient outcomes and enhance our understanding of the disease, as the interplay between genetic and nongenetic factors. Developing this clinical comprehensive PD panel also serves as a platform for incorporating new discoveries into clinical practice timely.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinal-comprehensive-next-gen-gene-panel-for-parkinsons-disease/