Abstract
The aim of the present study was to check the frequency of genetic variants in exons 8, 11, 13, and 17 of the WDR36 gene among primary open angle glaucoma (POAG) patients from Punjab, Pakistan, and to perform the in silico analysis of identified variants on protein function. Ninety-two individuals affected with primary open angle glaucoma were enrolled for this study. The clinical investigation involved the examination of the optic nerve head, visual field loss and elevated intraocular pressure (IOP). Selected exons (8, 11, 13, and 17) of the WDR36 gene was screened by Sanger sequencing. Sequencing results revealed a previously reported missense mutation p.D658G in exon 17 in two out of ninety-two POAG patients, while no mutation has been identified in the exons 8, 11, and 13. To predict the structural and functional effect of the p.D658G variant, SIFT, Polyphen-2, PROVEAN, mutation taster, I-mutant 3.0, and MuPRO were used. The MODELLER-CABS based hybrid approach was used for protein structure modelling. In silico analysis predicted the p.D658G variant to be deleterious, and it may affect the stability of protein and protein-protein interaction. The findings of this study suggested that the genetic variant p.D658G of the WDR36 gene is a rare genetic cause of POAG in Pakistani patients. The in silico tools predicted the variant p.D658G to be deleterious; however the modelled normal and mutant structure showed no effect on protein structure and function. To further confirm the pathogenic effect of this SNP, in vivo experiments, X-ray Crystallography of the WDR36 protein and population-based studies are needed.
Published Version
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