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Myocilin Mutations in a Zambian Population Attending Selected Referral Eye Health Facilities

Purpose: Research has shown that primary open-angle glaucoma (POAG) in Zambia has an earlier age of onset and is more clinically severe than in Europe and the United States of America. Mutations of Myocilin have been reported to be associated with POAG in multiple populations. We therefore, investigated the role of myocilin gene mutations in Primary Open Angle Glaucoma in a Zambian population. Methods: The unrelated POAG patients and unaffected controls seen at the University Teaching Hospitals Eye Hospital, Kitwe Teaching Eye Hospital and Lusaka Eye Hospital were recruited for this study. Glaucoma specialists from the participating institutions ascertained all POAG and control patients. Age, sex and ethnicity matched unaffected controls were obtained in patients with an IOP < 22 mm Hg, clear ocular media and normal-appearing optic nerve heads. A complete eye examination, including visual field assessment, was performed in all cases. Genomic DNA was extracted from whole peripheral blood, then subjected to polymerase chain reaction to amplify exons, flanking introns and promoter regions of the myocilin gene. The amplified products were screened for base mutations by autosequence based on the Sanger method. The study used the chi square test and conditional logistic regression to compare the cases and controls. Identified mutations were compared to known myocilin mutations. Results: Unrelated 165 POAG patients and unaffected 173 controls enrolled for the study. The analysis revealed four variants of myocilin mutations in 49 participants which included one synonymous (silent) mutation (Thr474Thr; 45/338) and three missense mutations (Ala446Thr; 16/338), (Leu158Arg; 4/338) and (Arg342Lys; 1/338). The prevalence of myocilin (MYOC) gene mutations in this study was 14.5% (49/338). The study observed two previously reported mutations, Ala446Thr and Arg342Lys, as glaucoma causing mutations. The variant (Lys158Arg) observed in the study was a novel finding. These mutations were detected in age, sex and ethnically matched controls. The missense mutation, Ala446Thr, was found in eight cases and eight controls. Twenty (20) controls and 25 cases had the synonymous or silent (neutral) mutation, (Thr474Thr). Conclusions: The myocilin mutations represent a prevalence of 14.5 in a Zambian population. The Leu158Arg seems to represent novel glaucoma, causing missense mutation. Mutations in myocilin appear to play a big role in the pathogenesis of POAG in a Zambian population.