Parkinson's Disease in Saudi Patients: A Genetic Study

• Published in: PloS one Vol. 10; no. 8; p. e0135950
• Main Authors: Al-Mubarak, Bashayer R, Bohlega, Saeed A, Alkhairallah, Thamer S, Magrashi, Amna I, AlTurki, Maha I, Khalil, Dania S, AlAbdulaziz, Basma S, Abou Al-Shaar, Hussam, Mustafa, Abeer E, Alyemni, Eman A, Alsaffar, Bashayer A, Tahir, Asma I, Al Tassan, Nada A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.08.2015; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Analysis; Basal ganglia; Brain diseases; Brain research; Case-Control Studies; Central nervous system diseases; Child; Child, Preschool; Dopamine receptors; Dosage; Etiology; Family medical history; Female; Gene dosage; Gene expression; Gene sequencing; Genes; Genetics; Genomes; Humans; Infant; LRRK2 protein; Male; Medical research; Mesencephalon; Middle Aged; Molecular chains; Molecular modelling; Movement disorders; Mutation; Neurodegenerative diseases; Neurology; Neurosciences; Oxidative stress; PARK7 protein; Parkin protein; Parkinson Disease - genetics; Parkinson's disease; Patients; Populations; Proteins; PTEN-induced putative kinase; Saudi Arabia; Screening; Saudi Arabia; United States > US; Riyadh Saudi Arabia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0135950

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.