The myocilin GLN368Stop mutation in normal tension glaucoma

Abstract

Purpose : To determine the role of the myocilin GLN368Stop mutation in normal tension glaucoma (i.e. primary open angle glaucoma that occurs at intraocular pressures <22 mm Hg). The GLN368Stop mutation is of particular interest because it is the most common known molecular cause of primary open angle glaucoma.

Methods : Cohorts of patients with normal tension glaucoma (n = 748) and control subjects (n = 1780) were tested for the most common myocilin mutation, GLN368Stop, which has been previously associated with glaucoma that occurs with high intraocular pressures (i.e. 30 mm Hg). The GLN368Stop mutation was assessed with either whole exome analyses or with quantitative real-time PCR. All positive results were confirmed with Sanger sequencing.

Results : Seven of 748 (0.94%) normal tension glaucoma patients and 7 of 1780 (0.39%) controls were found to have a GLN368Stop myocilin mutation. The GLN368Stop mutation was 2.4X more frequent in NTG patients than in control subjects, however, this difference was not statistically significant (p > 0.05).

Conclusions : Myocilin mutations have been previously associated with primary open angle glaucoma that occurs with high intraocular pressure. Our pilot study suggests that some cases of normal tension glaucoma may also be caused by myocilin mutations. A larger study with greater power will be necessary to determine if the GLN368Stop mutation is statistically associated with normal tension glaucoma.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.