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

Ehab. S. El Desoky; Eman. M. Khedr; Mohamed. S. Khalil; Thomas Gasser

Ehab. S. El Desoky Department of Pharmacology, Faculty of Medicine, Assiut University Hospital, Assiut, Egypt.
Eman. M. Khedr Department Neurology, Faculty of Medicine, Assiut University Hospital, Assiut, Egypt.
Mohamed. S. Khalil Department Clinical Pathology, Faculty of Medicine, Assiut University Hospital, Assiut, Egypt.
Thomas Gasser Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of T�bingen, T�bingen, Germany.

Keywords: Leucin-rich repeat kinase 2 G2019S, mutation, parkinson's, Egyptians

Abstract

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 Parkinsons 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 Tingen, Tingen, 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 Parkinsons disease to reach a real incidence of that mutation and if it has (or not) a correlation to causation and course of Parkinsons disease among Egyptians. Also, genetic assessment of other points of mutations other than G2019S on LRRK2 is required among Egyptians with PD.