Spotlight on Leucin-Rich Repeat Kinase 2 (LRRK2) G2019S Mutation and Parkinson's Disease in Egyptians | Chapter 06 | New Insights into Disease and Pathogen Research Vol. 1
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. PCR-genotyping 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.
Author(s) Details
Professor Ehab S. EL
Desoky M.D, PhD
Department of Pharmacology,
Faculty of Medicine, Assiut University Hospital, Assiut, Egypt.
Dr. Thomas Gasser
Department of
Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research,
University of Tübingen, Tübingen, Germany.
View Volume: https://doi.org/10.9734/bpi/nidpr/v1
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