Myocilin Mutations in Patients With Normal-Tension Glaucoma

Area of Science:

• Ophthalmology
• Genetics
• Molecular Biology

Background:

• Mutations in the myocilin (MYOC) gene are a common cause of primary open-angle glaucoma, typically associated with high intraocular pressure (IOP).
• The MYOC p.Gln368Ter mutation has been identified in primary open-angle glaucoma cases with elevated IOP.
• The role of this mutation in normal-tension glaucoma (NTG), characterized by normal IOPs (≤21 mm Hg), has not been previously investigated.

Purpose of the Study:

• To investigate the prevalence and association of the MYOC p.Gln368Ter mutation in patients diagnosed with normal-tension glaucoma (NTG).

Main Methods:

• A case-control study was conducted using two cohorts comprising patients with NTG and healthy controls from the United States and England.
• Genotyping for the p.Gln368Ter mutation was performed using real-time polymerase chain reaction, Sanger sequencing, or analysis of genome-wide association study/whole-exome sequence data.
• Statistical analysis, including the Fisher exact test, was employed to compare mutation frequencies between NTG cases and controls.

Main Results:

• The p.Gln368Ter mutation was detected in 0.91% of NTG patients and 0.33% of controls in cohort 1 (P=.03).
• In cohort 2, the mutation was found in 0.71% of NTG patients and 0.38% of controls (P=.15).
• Pooled analysis of both cohorts revealed a statistically significant association between the p.Gln368Ter mutation and NTG (odds ratio, 2.3; P=.04).

Conclusions:

• The MYOC p.Gln368Ter mutation was identified in patients with normal-tension glaucoma (IOP ≤21 mm Hg).
• Although found at a lower frequency than in high-IOP glaucoma, the mutation's presence in NTG patients suggests a potential role in glaucoma development across different IOP levels.
• These findings indicate that the p.Gln368Ter mutation may be a risk factor for glaucoma in both normal and elevated IOP conditions.