Objective: To evaluate effectiveness of panel testing of known Parkinson’s disease (PD) related genes in clinical practice.

Background: It is widely recognised that monogenic forms of PD are responsible for development of clinical symptoms in 5-10% of patients, but due to the polygenic associations establishing the genetic cause in hereditary parkinsonism have not been widely available in clinical practice. Recent advantages in molecular genetics – emerging of massive parallel sequencing techniques- allow simultaneous analysis of several genes and therefore allow specification of genetic cause, mode of inheritance and familial recurrence risks in polygenic disorders (including PD) cost-effectively in clinical practice. Currently over 40 genes have a major causative role in development of PD and establishing the genetic background is helpful in patient’s management in terms of prognosis and genetic consultation.

Method: 22 subsequent patients with clinically suspected monogenic parkinsonism were tested for changes in 32 genes associated with hereditary PD. Genes were selected according to strong associations described in the literature and gene panel was regularly updated as new associations emerged. DNA was extracted from blood and sequenced by next-generation sequencing (NGS) and likely pathogenic variants were confirmed by Sanger sequencing. All patients with likely pathogenic variants were referred to genetic consultation.

Results: Genetic cause of PD was established in 4 patients (18%) – mutation in LRRK2 was present in all of them. Additionally previously undescribed variants in disease associated genes were detected in 2 patients- 1 patient with probable Perry syndrome had intronic variant in DCTN1 gene and the other patient had heterozygous variant in DNAJC6 gene. Complex genotypes with rare variants present in 2 different genes were detected in 3 patients and known risk factor – a heterozygous mutation in GBA gene was detected in 1 patient.

Conclusion: The panel testing of genes related to the monogenic PD is highly informative and cost-effective in diagnosing hereditary forms of disease in clinical setting. Panel testing using NGS analysis is flexible approach for genetic risk estimation with the potential of giving new insights to the genetic background of PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/genetic-panel-testing-in-parkinsons-disease/