Identification and genotype phenotype correlation of novel mutations in SIX6 gene in primary open angle glaucoma

ABSTRACT

Background: Recently SIX1 and SIX6 genes have been associated with primary open angle glaucoma (POAG). This study was planned to do mutation screening in SIX1 and SIX6 genes in North Indian POAG patients and correlate with clinical phenotypes.

Materials and Methods: SIX1 and SIX6 genes were amplified by PCR and sequenced in 115 POAG cases and 105 controls. Four pathogenecity prediction tools (MutationTaster, PolyPhen-2 HumDiv, PolyPhen-2 HumVar and SIFT) were used to predict the pathogenicity of the missense mutations. Protein modeling studies were done to predict the effect of the missense mutations on the protein structure and function.

Results: Two novel mutations p.R116G and p.R116E were observed in the SIX6 gene of patients with POAG. The mutations p.R116G and p.R116E were predicted to be pathogenic and replacement of R116 by G or E might lead to loss of interaction between DNA and R116 of wild type SIX6 protein. The patients with the mutation p.R116E had significantly more visual field damage (MD) and early age of onset of the disease. No sequence variations were observed in the SIX1 gene.

Conclusion: These results expand the mutation spectrum of SIX6 gene and suggest that SIX6 gene plays an important role in POAG pathogenesis.

KEYWORDS:

• Glaucoma
• SIX1
• SIX6
• visual field

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This work was funded by the Indian Council of Medical Research (ICMR), Government of India.