ABSTRACT
PURPOSE: Investigators have noted that primary open-angle glaucoma (POAG) in West Africa has an earlier age of onset and appears to be more clinically severe than in the United States and Europe. Primary open-angle glaucoma patients with mutations in myocilin have a similar phenotype. Therefore, we investigated the role of mutations in myocilin in patients with POAG in a West African population. MATERIALS AND METHODS: Patients seen at the Emmanuel Eye Clinic in Accra, Ghana, were recruited for this study. Informed consent was obtained from all study patients. Glaucoma specialists from the sponsoring institution (PC, LWH, or RRA) ascertained all POAG and control patients. Age-matched unaffected controls were obtained in patients with an IOP < 22 mm Hg and normal-appearing optic nerves. PCR amplification of each of the three myocilin exons was performed. Denaturing high-performance liquid chromatography (Transgenomics Corp.) was used to detect allelic differences and samples demonstrating a mobility shift were sequenced in both directions. RESULTS: Ninety unrelated affecteds with POAG and 76 control patients were recruited. Four individuals with severe POAG were found to have novel missense mutations in exon 3. Two exhibit an Asp380Asn mutation and two an Arg342Lys mutation. These changes were not detected in 152 ethnically matched control chromosomes. Fourteen affected individuals and eight controls exhibit a translationally silent polymorphism in codon 325 (Thr325Thr). CONCLUSIONS: A total of 4.4% of patients with POAG have novel disease-associated mutations in myocilin. Mutations in myocilin appear to play a limited role in the pathogenesis of POAG in this region of West Africa.
