Using whole exome sequencing in determining the genetic cause of Parkinson disease in an Iranian family

Abstract

Objective: Parkinson?s disease (PD) is the second most common neurodegenerative disorder. Identification of PD and Parkinson-plus genes will inform us for further elucidation of the disease mechanisms and therapeutic approaches. Accordingly, in this study, an Iranian pedigree with familial PD was selected to investigate the underlying genetic causes by whole exome sequencing (WES). Methods: WES was performed on two affected family members to identify shared pathogenic putative variants. WES finding was confirmed by Sanger sequencing in two sisters. Results: Prioritizing genes related to parkinsonism identified one homozygous pathogenic mutation: g.20655C>T, c.1366C>T (p.Q456X) on the 7th exon of PINK1 gene. This homozygous C to T transition which introduces a premature termination codon (PTC) was predicted to be disease causing. Conclusion: In the present study, we report the successful application of WES to identify the molecular pathogenesis of autosomal recessive PD, which is a genetically heterogeneous disorder. The presence of this mutation in patients with family history draws attentions to the importance of genetic counseling.