Paucity of optineurin gene variants in Indian juvenile open-angle glaucoma patients

In the current study, we have screened the OPTN gene in a cohort of unrelated juvenile open-angle glaucoma (JOAG) patients negative for possible pathogenic variants in CYP1B1 and MYOC genes.

Polymerase chain reaction (PCR) amplification and sequencing were employed to identify nucleotide variants within the coding sequence and intron-exon boundaries of the OPTN gene in 85 JOAG patients and 100 controls. A pathogenicity prediction of identified variants was performed by six distinct online algorithms. Possible structural alterations caused by pathogenic variants were investigated using GOR IV, PyMol, ChimeraX, and molecular dynamics simulations using Gromacs software.

PCR amplification and sequencing revealed a total of 27 variations, encompassing eight missense, six synonymous, and 13 intronic changes. Out of the 85 patients, three JOAG individuals exhibited possible pathogenic variants. A novel missense variant p.(Q518L) was also observed and registered at NCBI with accession number PP898303. Computational algorithms identified three potential pathogenic variants. These variants induce disruptions and structural alterations which in turn compromise their functionality. This ultimately leads to retinal ganglion cells death and the eventual manifestation of glaucomatous damage resulting in vision loss.

This is the first report showing the involvement of pathogenic OPTN gene variants in JOAG cases from North Indian population which was unknown till now. This study provides population-specific data on genetic contribution of OPTN genes in JOAG pathogenesis. Genetic investigations like this may help in the understanding of disease pathogenesis and development of therapy for glaucoma management/treatment in the near future.