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Alex W. Hewitt, MBBS; Sonya L. Bennett, FRANZCO; Julia E. Richards, PhD; David P. Dimasi, BBiotech; Adam P. Booth, FRCOphth, PhD; Chris Inglehearn, PhD; Rashida Anwar, PhD; Tetsuya Yamamoto, MD; John H. Fingert, MD, PhD; Elise Héon, MD; Jamie E. Craig, DPhil, FRANZCO; David A. Mackey, MD, FRANZCO

Arch Ophthalmol. 2007;125(1):98-104.

Objective  To determine the phenotype of an Australian pedigree with the myocilin (MYOC) Gly252Arg mutation, comparing it with other pedigrees carrying the same mutation.

Methods  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 MYOC gene.

Results  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 ± SD, 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 MYOC Gly252Arg mutation and a novel MYOC Gly244Val variant.

Conclusions  Although a common founder for Gly252Arg across Caucasian subjects was found, the phenotype from this Australian MYOC mutation–carrying pedigree is less severe than previously described. The severity of glaucoma caused by the Gly252Arg mutation may be similar to the Thr377Met MYOC mutation, yet is more severe than the most common Gln368Stop mutation.

Clinical Relevance  Since its implication in glaucoma, much work has been performed investigating the clinical features of MYOC-related glaucoma. Given the strong genotype-phenotype correlations with MYOC 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 MYOC Gly252Arg is less severe than previously described in other pedigrees with this specific mutation.

Author Affiliations: Clinical Genetics Unit, Eye Research Australia, University of Melbourne, Royal Victorian Eye & Ear Hospital, Melbourne (Drs Hewitt and Bennett); Department of Ophthalmology, Flinders Medical Centre, Flinders University, Adelaide, Australia (Drs Hewitt, Craig, and Mackey, and Mr Dimasi); Department of Ophthalmology, University of Michigan, Ann Arbor (Drs Richards and Booth); Leeds Institute of Molecular Medicine, Wellcome Trust Brenner Building, St James's University Hospital, Leeds, England (Drs Booth, Inglehearn, and Anwar); Department of Ophthalmology, Gifu University, Gifu, Japan (Dr Yamamoto); Department of Ophthalmology and Visual Sciences, University of Iowa Hospitals and Clinics, Iowa City (Dr Fingert); Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, Toronto, Ontario (Dr Héon); and Department of Ophthalmology, University of Tasmania, Royal Hobart Hospital, Hobart, Australia (Dr Mackey).

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