Myocilin Gly252Arg mutation and glaucoma of intermediate severity in Caucasian individuals

<p><strong>Objective:</strong> To determine the phenotype of an Australian pedigree with the myocilin (<i>MYOC</i>) Gly252Arg mutation, comparing it with other pedigrees carrying the same mutation.</p> <p><strong>Methods:</strong> All recruited subjects underwent a comprehensive clinical examination, including optic disc assessment, applanation tonometry, and visual field measurement. Mutation analysis was performed through direct sequencing. Haplotype analysis was performed using microsatellite markers around the <i>MYOC</i> gene.</p> <p><strong>Results:</strong> Eight Gly252Arg mutation carriers with glaucoma were identified from the same pedigree. Carriers' mean ± SD age at diagnosis was 46.3 ± 11.4 years (range, 31-60 years). Highest recorded intraocular pressure ranged from 27 to 42 mm Hg (mean ± D, 32.4 ± 5.6 mm Hg). Cup-disc ratios in the worst eye ranged from 0.6 to 0.9. Six of the 8 individuals had undergone filtration surgery. A common founding haplotype between MY5 and D1S218 was found for Caucasian individuals tested with this mutation. One subject was compound heterozygotic for the <i>MYOC</i> Gly252Arg mutation and a novel <i>MYOC</i> Gly244Val variant.</p> <p><strong>Conclusions:</strong> Although a common founder for Gly252Arg across Caucasian subjects was found, the phenotype from this Australian <i>MYOC</i> mutation-carrying pedigree is less severe than previously described. The severity of glaucoma caused by the Gly252Arg mutation may be similar to the Thr377Met <i>MYOC</i> mutation, yet is more severe than the most common Gln368Stop mutation.</p> <p><strong>Clinical Relevance:</strong> Since its implication in glaucoma, much work has been performed investigating the clinical features of <i>MYOC</i>-related glaucoma. Given the strong genotype-phenotype correlations with <i>MYOC</i> disease-causing variants, health care professionals armed with such molecular information are able to accurately counsel patients on their likely disease course. Our work suggests that the disease associated with <i>MYOC</i> Gly252Arg is less severe than previously described in other pedigrees with this specific mutation.</p>