Spotlight on Leucin-Rich Repeat Kinase 2 (LRRK2) G2019S Mutation and Parkinson's Disease in Egyptians

Aim: Many causative genes and susceptibility loci have been identified to be associated with
Parkinson's disease (PD) in different ethnic populations. One of these genes is the Leucin-rich repeat
kinase 2 (LRRK2) gene. The G2019S substitution in that gene is the most common mutation identified
to co-segregates with PD. One of the significant mutations in LRRK2 linked to PD is the G2019S
which has been found associated with neuronal impairment and loss of dopaminergic neurons.
Furthermore, new monoclonal antibody assay has been developed to quantify LRRK2 G2019S kinase
pathway activity in Parkinson’s patients. This type of mutation has been investigated in the North part
of Egypt (Alexandria and nearby region), which showed an incidence of 9.7% of heterozygous
mutation in LRRK2 G2019S in a sample of Egyptians with sporadic PD. We investigated the same
mutation in 69 Egyptian patients with sporadic PD and 96 ethnically matched controls who all were
inhabitants of Upper Egypt to find out if it could be a susceptibility gene for PD among Egyptians.
Place and Duration of Study: Departments of pharmacology, neurology, and clinical pathology,
Assiut University (Egypt) and Department of Neurodegenerative Diseases, Hertie-Institute for Clinical
Brain Research, University of Tübingen, Tübingen, Germany between June 2010 and September
2011.
Methodology: Sixty nine patients with PD of sporadic type and ninety six controls were included in
the study and all were inhabitants of Assiut Governorate and nearby region in Upper Egypt. PCRgenotyping
analysis for the point mutation G2019S in the exon 41 was performed and presence or
absence of mutation was confirmed by direct sequencing of the probands identified of the DNA.
Results: Genotyping analysis and sequencing of DNA showed only one patient who was carrier to
the mutation G2019S (1/69; incidence: 1.45%) and it was of heterozygous style. The rest of subjects
(patients and control) were not carrying the mutation. This rarity of this kind of mutation among the
Egyptian sample studied suggests that it may be a rare cause of PD in Upper Egypt region. However,
if it is observed, it may have a trend of heterozygosity genotyping style as previously defined in the
Egyptians living in the North region of Egypt.
Conclusion: The very low incidence of G2019S mutation in Egyptians living in Upper Egypt
compared to Egyptians inhabitants in North Egypt suggests a prospective multicenter study on a large
number of Egyptians with Parkinson’s disease to reach a real incidence of that mutation and if it has
(or not) a correlation to causation and course of Parkinson’s disease among Egyptians. Also, genetic
assessment of other points of mutations other than G2019S on LRRK2 is required among Egyptians
with PD.