Comprehensive analysis of myocilin variants in east Indian POAG patients - PubMed (original) (raw)

Comprehensive analysis of myocilin variants in east Indian POAG patients

Deblina Banerjee et al. Mol Vis. 2012.

Abstract

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.

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Figures

Figure 1

Figure 1

Novel changes identified in myocilin in POAG patients. All the changes were identified in the heterozygous condition. The mutated base is indicated with an arrowhead in the chromatograms. A: The chromatogram on the left demonstrates location of a synonymous variant (c.372 G>C, Leu124Leu) and a deletion mutation (c.375, del G, R125SfsX158). On the right, the cartoons show all the known domains of normal MYOC and the truncated protein resulting from the deletion, including aberrant 33 amino acids at the COOH-terminal end. B: The chromatogram on the left demonstrates location of a deletion mutation (c.819, del C, D273DfsX344). On the right, the cartoons demonstrate the known domains of normal MYOC and the truncated protein resulting from the deletion, including aberrant 71 amino acids at the COOH-terminal end. C: The chromatogram on the left demonstrates location of a nonsynonymous variant (c.992 C>T, Ser331Leu). On the right, conservation status of the residue (indicated by arrowhead) is shown in homologous protein in other species.

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