PLA2G6 and NOTCH3 variants associated with familial Parkinson’s disease in two suspected families based on whole genome sequencing

چکیده مقاله

Introduction: Parkinson’s disease is a progressive, destructive, and long-term disorder of the central nervous system that mainly disrupts the movement system of the body. In the advanced stages of Parkinson’s disease, sometimes dementia is also common. In the present study, two patients from two families of five suspected to have Parkinson’s disease were investigated to identify pathogenic variants. Methods and materials: After confirmation by a neurologist and a geneticist, blood samples were taken. Then DNA was extracted from the target sample and analyzed by exome sequencing. The VCF file of WES was extracted using the databases 1000 Genomes, EXAC, NHLBI Sequencing project, GMA variom, HIX (Healthy Exoues), CAD and also with the help of bioinformatics analysis using the HGMD site, all the genes and mutations of this disease were extracted. Then, using the POLY PHEN and SIFT sites, the effect of mutations in causing the disease was investigated separately. Results: In total, we obtained 3420 variants. After several stages of filtering, 181 variants were reported in 11 genes related to Parkinson’s disease, of which 4 variants were new. Two variants related to the PLA2G6 gene and 2 variants related to the NOTCH3 gene, were introduced as pathogenic variants after data analysis using Finch TV software with the help of trench sequencing of NOTCH3 and PLA2G6 gene variants. Conclusion: It was conducted that the variant reported as heterozygous mutations in NOTCH3 and PLA2G6 genes can be related to the occurrence of Parkinson’s disease.