RESUMEN
PURPOSE: Mutations in the myocilin gene (MYOC) account for 2%-4% of primary open angle glaucoma (POAG) cases. To date, a limited number of Indian POAG patients have been analyzed for the contribution of the gene towards the disease pathogenesis. In this study we provided a comprehensive analysis of a total of 765 eastern Indian POAG patients. METHODS: In the present study 450 POAG patients and 208 ethnically matched controls were screened for the coding region of MYOC by using the polymerase chain reaction-direct sequencing approach; 315 POAG patients were analyzed in a previous study. Thus, our total patient cohort considering both the studies was 765. In addition, 1 kb upstream region of the gene was also examined for variants in a subset of 250 patients and 100 control samples. RESULTS: Analysis of MYOC coding regions in 450 POAG patients revealed 10 novel variations including 2 frame-shift (R125SfsX158 and D273DfsX344) and 3 nonsynonymous changes (Arg33Lys, Ser331Leu, and Asp395Glu), 3 reported mutations and 4 reported polymorphisms. Gln48His, which has to date been reported only from Indian subcontinent, was identified in 4 individuals among 450 patients, taking the count to 7 individuals among 765 patients harboring the same mutation in eastern Indian cohort. Screening of 1 kb upstream region of MYOC in limited number of individuals yielded 5 variants but none are likely to contribute to the pathogenesis of the disease. CONCLUSIONS: MYOC mutations were found to account for 3% of POAG cases in our entire cohort (n=765) and Gln48His is the most common defect. This study, for the first time, reports the presence of deletion mutations in Indian patients, and represents the largest study performed in a single cohort in the Indian population.