Parkinson’s Disease in Saudi Patients: A Genetic Study

Abstract

Parkinson’s disease (PD) is one of the major causes of parkinsonism syndrome. Its characteristic motor symptoms are attributable to dopaminergic neurons loss in the midbrain. Genetic advances have highlighted underlying molecular mechanisms and provided clues to potential therapies. However, most of the studies focusing on the genetic component of PD have been performed on American, European and Asian populations, whereas Arab populations (excluding North African Arabs), particularly Saudis remain to be explored. Here we investigated the genetic causes of PD in Saudis by recruiting 98 PD-cases (sporadic and familial) and screening them for potential pathogenic mutations in PD-established genes; SNCA, PARKIN, PINK1, PARK7/DJ1, LRRK2 and other PD-associated genes using direct sequencing. To our surprise, the screening revealed only three pathogenic point mutations; two in PINK1 and one in PARKIN. In addition to mutational analysis, CNV and cDNA analysis was performed on a subset of patients. Exon/intron dosage alterations in PARKIN were detected and confirmed in 2 cases. Our study suggests that mutations in the ORF of the screened genes are not a common cause of PD in Saudi population; however, these findings by no means exclude the possibility that other genetic events such as gene expression/dosage alteration may be more common nor does it eliminate the possibility of the involvement of novel genes.

Levodopa-Carbidopa Intestinal Gel Infusion Therapy in Advanced Parkinson's Disease: Single Middle Eastern Center Experience

“…However, we did not find any significant difference in improvement scores among the different age groups, which may be attributed to the limited number of patients included in our study. Of interest, the JP case in our cohort was proven to carry a PARK2 ( PARKIN p.T240M) mutation [23]. …”

“…Interestingly, we had a great number of YOPD and one case of JP in our study, which was not seen in other populations. This can be attributed to the high consanguinity and unique structure of the Saudi population, as young people form a majority of the population; we have recently reported high numbers of these subgroups among Saudi PD patients [23]. Therefore, a marked improvement is expected in such individuals due to the higher motivational status and absence of other comorbidities.…”

Parkinson's Disease in the Gulf Countries: An Updated Review

“…This could be attributed to the ancestral differences between GCC Arabs and North African Arabs, the latter community being much more closely associated with Berber ancestry [13] . The absence of LRRK2 G2019S mutations in the Saudi population studied by Al-Mubarak et al [15] further demonstrates the genetic distinction between GCC Arabs and North African Arabs. These findings, however, do not prove the specificity of LRRK2 G2019S mutations to North African Arabs, and are a reminder of the need for further exploration of the role of the genetics of PD in the GCC.…”

Copy number variability in Parkinson’s disease: assembling the puzzle through a systems biology approach

“…For this reason, more than 200 putative pathogenic mutations have been reported so far, affecting numerous ethnic populations (Wang et al 2010, 2013; Keyser et al 2010; Nuytemans et al 2009; Chaudhary et al 2006; Klein et al 2005; Shadrina et al 2007; Choi et al 2008; Pankratz et al 2009; Kay et al 2010; Guerrero Camacho et al 2012; Moura et al 2012; Yonova-Doing et al 2012; Chu et al 2014; Al-Mubarak et al 2015; Guo et al 2015; Mata et al 2005). The PARK2 mutation spectrum includes homozygous or compound heterozygous missense and nonsense point mutations, as well as several exon rearrangements (both duplications and deletions) involving all the originally cloned 12 exons and the promoter region.…”