Myocilin mutations among primary open angle glaucoma patients of Kanyakumari district, South India

Abstract

Purpose: Glaucoma can be defined as optic neuropathy leading to irreversible blindness if not treated in time. Primary open angle glaucoma (POAG) is the most common form of glaucoma. The myocilin (MYOC) gene has been found to mutate in both sporadic and familial cases of POAG worldwide. About 90% of these mutations have been seen to cluster at exon III of the gene. There are documented reports of mutations in the MYOC gene among POAG patients from different parts of India. The southernmost tip of the Indian subcontinent (Kanyakumari district) has remained isolated from all these studies. The aim of this study was to indicate or rule out the disease causative role of the MYOC gene mutations in these patients by screening the MYOC gene for mutations among POAG patients of the Kanyakumari district.

Methods: One hundred POAG patients from the Kanyakumari District of South India were recruited for the study. The MYOC gene was screened using the PCR-SSCP methodology followed by DNA sequencing. The sequences were analyzed using BLAST. Secondary structures of the amino acid sequences with a variation were predicted.

Results: Two probable disease-causing variations (mutations), Ser331Thr and Pro370Leu, were each observed in one patient apiece. Two polymorphisms, (Tyr347Tyr and Thr325Thr) were also observed in the patients. Ser331Thr is a novel conservative change while Pro370Leu is a widely reported mutation with an associated severe disease phenotype.

Conclusions: The presence of the mutations in the patients suggests the causative role of the MYOC gene among POAG patients in the Kanyakumari district of India. The mutation frequency of 2% corresponds well with the other reports from India and other countries. However, the mutation rate reported from a population in the eastern part of India was much higher. Screening of patients from different parts of India is essential to estimate the overall mutation frequency. More functional studies on the MYOC gene are required to elucidate the pathophysiology of POAG.

Figure 1

Heterozygous Ser331Thr mutation and Thr325Thr polymorphism in the MYOC gene. Chromatogram sequence derived from patient Ngl 12 with the T>A transversion and G>A transition (indicated by arrows) compared to the normal control.

Figure 2

Heterozygous Pro370Leu mutation in the MYOC gene. Comparison of chromatogram sequences derived from patient R6 and normal control. Arrow marks the C>T transition compared to the normal control.

Figure 3

Secondary structure prediction of the mutant sequence (Ser331Thr) using the GOR method. Comparison between the predicted secondary structures of control (A) amino acid sequences of myocilin and the amino acid sequences of myocilin with the Ser331Thr variant (B; only the region where there was a change in the predicted secondary structure has been shown).