Genetic Landscape of Monogenic Parkinson's Disease in the African Population-A Systematic Review

Most genetic studies on Parkinson's disease (PD) have been conducted in populations of European descent. The African population is under-represented in PD genetics research. The aim of this systematic review is to give a comprehensive and up-to-date overview of monogenic PD in Africa.

A systematic literature search was conducted across PubMed, Scopus, and Web of Science databases until July 2025. Studies that analyzed at least one of 13 well-established monogenic PD genes in individuals of African ancestry were included. Data were analyzed separately in North African (NA) and Sub-Saharan African (SSA) countries.

Among 6303 PD patients from 64 included studies, 720 (11.42%) were diagnosed with monogenic PD caused by 34 (likely) pathogenic variants in 7 genes. Autosomal dominant LRRK2-related PD was by far the most common diagnosis observed in 641 patients (10.17%) and nearly exclusively driven by the p.(Gly2019Ser) founder variant in NA with a weighted pooled prevalence of 28% (95% CI, 19%-37%). Autosomal recessive PD linked to PINK1 (0.57%) or PRKN (0.32%) and autosomal dominant GBA1-related PD (0.29%) were rare and showed no strong differences between NA and SSA. ATP13A2-, SYNJ1-, and PARK7-related autosomal recessive (atypical) PD was very rare (0.08%) and only observed in NA.

Monogenic PD in Africa shows allelic and locus heterogeneity with a very strong contribution of the LRRK2 p.(Gly2019Ser) founder variant in NA. Notably, in more than 98% of SSA PD patients no molecular cause was found. Next-generation sequencing-based technology could uncover novel causative variants that may be specific to these populations. © 2026 International Parkinson and Movement Disorder Society.