The Gly252arg Myocilin Mutation Confers Glaucoma of Intermediate Severity

Abstract

Purpose: : The purpose of this study is to examine the phenotype of an Australian pedigree with the Gly252Ala myocilin mutation and compare it to previously published descriptions of pedigrees carrying the same mutation.

Methods: : All recruited subjects underwent a comprehensive clinical examination, including: optic disc assessment; pachymetry; applanation tonometry; and visual field measurement. All data presented are the mean ± standard deviation. Mutation analysis was performed through direct sequencing. Haplotype analysis was performed using microsatellite markers around the myocilin gene.

Results: : Eight glaucoma affected people were identified from the same Australian pedigree. Their mean age at diagnosis was 41.5 ± 8.2 years (range 32 to 57). The mean age at review was 61.4 ± 13.9 years. The highest recorded intraocular pressure (IOP) ranged from 26 to 42mmHg (mean: 31.8 ± 6.4). The median central corneal thickness was 521µm (range 492–560µm). Cup to disc ratios in the worst eye ranged from 0.6 to 0.9. Five of these individuals have undergone filtration surgery. The mean age at glaucoma diagnosis in the published literature for Scottish and American patients with the Gly252Ala myocilin mutation is approximately 30.1 ± 6.9 years, whilst the mean highest recorded IOP is 42.6 ± 14.2mmHg. A common founding haplotype between MY5 and D1S218 was found across our pedigrees and affected individuals living in Scotland and the United States of America.

Conclusions: : Although a common founder for this mutation across the world was found, the phenotype from this Australian Gly252Arg myocilin mutation carrying pedigree is less severe than described in the literature. Our results indicate that the Gly252Arg mutation may be less severe than the Thr377Met mutation though more severe than the Gln368Stop mutation.

Keywords: genetics • mutations