Leucine rich repeat kinase 2 (LRRK2) GLY2019SER mutation is absent in a second cohort of Nigerian Africans with Parkinson disease

Abstract

To date the LRRK2 p.G2019S mutation remains the most common genetic cause of Parkinson disease (PD) worldwide. It accounts for up to 6% of familial and approximately 1.5% of sporadic cases. LRRK2 has a kinase enzymatic domain which provides an attractive potential target for drug therapies and LRRK2 kinase inhibitors are in development. Prevalence of the p.G2019S has a variable ethnic and geographic distribution, the highest reported among Ashkenazi Jews (30% in patients with familial PD, 14% in sporadic PD, 2.0% in controls) and North African Berbers (37% in patients with familial PD, 41% in sporadic PD, and 1% in controls). Little is known about the frequency of the LRRK2 p.G2019S among populations in sub-Saharan Africa. Our group and others previously reported that the p.G2019S is absent in a small cohort of Nigerian PD patients and controls. Here we used Kompetitive Allele Specific PCR (KASP) assay to screen for the p.G2019S in a larger cohort of Black African PD patients (n = 126) and healthy controls (n = 54) from Nigeria. Our analysis confirmed that all patients and controls are negative for the p.G2019S mutation. This report provides further evidence that the LRRK2 p.G2019S is not implicated in PD in black populations from Nigeria and support the notion that p.G2019S mutation originated after the early human dispersal from sub-Saharan Africa. Further studies using larger cohorts and advance sequencing technology are required to underpin the genetic causes of PD in this region.

Fig 1. KASP assay cluster plots of the p.G2019S (rs34637584).

Genotypes cluster are visualised using SNP Viewer software. Samples marked red are p.G2019S homozygous (G:G), those marked green are p.G2019S heterozygous (G:A) and those marked black are non-template control (NTC). Plot (1-a) shows two distinctive clusters: the red cluster obtained from samples known to be homozygous (G;G) and the green cluster obtained from samples known to be heterozygous (G:A). Those samples with known genotypes were used to validate the assay prior to running the test samples. No known p.G2019S homozygous (A:A) sample was available to be included. Plots(1-b) and (1-c) show the data from the Nigerian cohort. All PD patients and controls are homozygous for the normal p.G2019S allele (G:G).