Low prevalence of MYOC mutations in UK primary open-angle glaucoma patients limits the utility of genetic testing

Abstract

Primary open angle glaucoma (POAG) affects 1% of people over age 40. Early detection and treatment can prevent blindness, but the disease is often asymptomatic until a late stage. Positive family history is an important risk factor and previous studies indicate that approximately 5% of POAG results from mutations in the myocilin ( MYOC) gene, raising the possibility of identifying individuals genetically predisposed to glaucoma. We collected DNA samples from 426 unselected UK POAG patients and analyzed them for MYOC mutations. The Q368X mutation was found in six patients (1.4%). No other mutations were identified, suggesting that amongst patients unselected for family history, the prevalence of MYOC mutations in the UK is lower than in other populations. Genetic and glaucoma screening was offered to first-degree relatives of these six probands (group 1) and of age/sex-matched mutation-negative controls (group 2). Of 11 group-1 relatives, three carried Q368X, one of whom already had glaucoma. Notably, of the 13 relatives in both groups who were mutation negative, one was already being treated for ocular hypertension. We therefore caution against changing glaucoma surveillance regimens in such individuals and suggest that routine untargeted genetic testing for MYOC mutations in patients with POAG would be of limited value until additional significant genetic risk factors are identified.

Glaucoma screening: current trends, economic issues, technology, and challenges

“…Many mutations throughout the coding region of the myocilin gene and its promoter region have been found in patients with OAG. The incidence of these mutations, however, varies significantly among different glaucoma populations and has been estimated to range from 1 to 4% [85][86][87][88].…”

Primary Open-Angle Glaucoma

“…Approximately 4% of cases of adult-onset primary open-angle glaucoma and more than 10% of juvenile-onset cases are associated with MYOC mutations. 3,4 These adult-onset cases feature an elevated intraocular pressure with resultant optic-nerve damage and visual loss, and they are clinically indistinguishable from cases of primary open-angle glaucoma in patients without MYOC mutations. 5 To address the mechanisms of optic-nerve damage, we broaden the discussion to include primary open-angle glaucoma with elevated intraocular pressure, with or without MYOC mutations.…”

Genetics of glaucoma

“…62 Similarly, in southern India, MYOC mutations were found in only 2% of patients with POAG. The hope was that those at greatest risk would be identified so that closer monitoring and timely intervention would prevent vision loss.…”