Comprehensive genetic screening of the South African Parkinson's disease study collection using the NeuroBooster...

Parkinson's disease (PD) is a complex neurodegenerative disorder with a substantial genetic influence. To better characterize the genetic landscape of PD in South Africa, we conducted the largest genetic screening to date for pathogenic single nucleotide and copy number variations (CNVs) using genotyping array data from 689 PD probands. We identified 16 unique missense variants, confirming 15 with Sanger sequencing, in 47 individuals across seven well-established PD genes, with GBA1 and PRKN being most frequent. Also in known PD genes, 18 variants of unknown significance were found. Additionally, CNV analysis using CNV-Finder revealed seven novel CNVs, five in PRKN and two in SNCA, of which, six were validated with Multiplex Ligation-dependent Probe Amplification. The findings highlight the contribution of both rare variants and structural rearrangements to PD in this underrepresented population. This study underscores the importance of expanding genetic research in African cohorts to improve global understanding of PD etiology.