The Assessment of RAB32 p. Ser71Arg Variant Prevalence in Parkinson's Disease Across Selected African, European, and South American Cohorts

Monogenic forms of Parkinson's disease (PD) have demonstrated a heterogeneous disorder involving multiple biological pathways.1 Familial forms of PD have been linked to variants in LRRK2, SNCA, VPS35, PARKIN, and PINK1. 1 Heterozygous GBA mutation carriers are associated with higher disease risk, earlier onset, and accelerated clinical progression. 1 Recently, RAB32 has emerged as a nominated PD gene.It encodes a Rab GTPase involved in mitochondrial and vesicular trafficking pathways.A rare substitution, p.Ser71Arg (rs200251693), has been proposed as a potential susceptibility factor.2,3 Reported carriers exhibit late-onset, levodopa-responsive parkinsonism with familial clustering; the only available autopsy case lacked Lewy bodies.1-3 Across published studies, RAB32 c.213C>G was detected in 0.22% to 2.3% of patients, primarily within Mediterranean and North American cohorts, and was absent in large East Asian datasets.This pattern suggests regional specificity and a possible shared Mediterranean haplotype.2-6 Limited data exist from several regions, including Eastern Europe, Ireland, sub-Saharan Africa, and South America.To address this gap, we screened 1730 patients with PD from Colombia (n = 188), Czech Republic (n = 31), Ecuador (n = 390), Ireland (n = 314), Nigeria (n = 52), Poland (n = 627), and Ukraine (n = 128).We analyzed 523 healthy control subjects from Colombia, Ireland, Poland, and Ukraine.Genotyping was performed at Mayo Clinic Florida.No carriers were identified (Table 1, Supporting Information Table S1, Fig. 1).Age at onset was typically in the late 50s to early 60s in the Czech, Ecuadorian, Nigerian, Polish, and Ukrainian groups, whereas the Colombian cohort demonstrated a younger disease onset.Family history was highest in Ireland (57%) and Ukraine (45%).Interestingly, Ireland exhibits one of the highest GBA carrier rates in Europe and a low LRRK2 mutation frequency.7 Absence of RAB32 p.Ser71Arg suggests that vesicular-trafficking pathways may play a lesser role in Irish PD relative to lysosomal pathways.7 Although case-control imbalance limits formal association testing, and may reduce statistical power, the - -------------------