A Next-Generation Sequencing Study in a Cohort of Sicilian Patients with Parkinson's Disease

Abstract

Parkinson's disease (PD) is a multisystem and multifactorial disorder and, therefore, the application of modern genetic techniques may assist in unraveling its complex pathophysiology. We conducted a clinical-demographic evaluation of 126 patients with PD, all of whom were Caucasian and of Sicilian ancestry. DNA was extracted from the peripheral blood for each patient, followed by sequencing using a Next-Generation Sequencing system. This system was based on a custom gene panel comprising 162 genes. The sample underwent further filtering, taking into account the allele frequencies of genetic variants, their presence in the Human Gene Mutation Database, and their association in the literature with PD or other movement/neurodegenerative disorders. The largest number of variants was identified in the leucine-rich repeat kinase 2 (LRRK2) gene. However, variants in other genes, such as acid beta-glucosidase (GBA), DNA polymerase gamma catalytic subunit (POLG), and parkin RBR E3 ubiquitin protein ligase (PRKN), were also discovered. Interestingly, some of these variants had not been previously associated with PD. Enhancing our understanding of the genetic basis of PD and identifying new variants possibly linked to the disease will contribute to improved diagnostic accuracy, therapeutic developments, and prognostic insights for affected individuals.

Keywords: NGS; Parkinson’s disease; gene variants; movement disorders.

Figure 1

Scheme differentiating patients listed in Table 1 by sex, “DM” and “DM?”, and the presence/absence of cognitive impairment. Each dot also reports the genes and the number of patients in whom it was found. Please see the text for gene abbreviations.

Figure 2

Diagram highlighting all variants and genes not associated with Parkinson’s disease but with other neurodegenerative or neuromuscular disorders (located outside the central circle), while PD-associated genes are represented within the circle (please also refer to Table S2 for additional details). Please see the legend of Table 1 for abbreviations.