METTL23 Variants and Patients With Normal-Tension Glaucoma

Area of Science:

• Ophthalmology
• Genetics
• Molecular Biology

Background:

• Normal-tension glaucoma (NTG) is a common form of glaucoma.
• Genetic factors play a significant role in the pathogenesis of NTG.
• Previous research has identified several genes associated with NTG, but the genetic basis remains incompletely understood.

Purpose of the Study:

• To investigate the frequency of pathogenic variants in the METTL23 gene in a cohort of patients with NTG.
• To determine if METTL23 variants are associated with an increased risk of developing NTG.

Main Methods:

• A case-control study was conducted with 331 NTG patients and 362 controls.
• Participants were recruited from the University of Iowa clinics.
• Exclusion criteria included a history of trauma, steroid use, or variants in known glaucoma genes (MYOC, TBK1, OPTN).

Main Results:

• Four unique METTL23 pathogenic variants were detected in 3 patients (0.91%) with NTG.
• Three of these variants were classified as likely pathogenic.
• The overall frequency of detected METTL23 variants was not statistically higher in NTG patients compared to controls.

Conclusions:

• Pathogenic variants in METTL23 are associated with autosomal dominant normal-tension glaucoma.
• METTL23 variants account for approximately 1% of NTG cases, comparable to other identified NTG genes.
• These findings suggest METTL23 is involved in a biological pathway contributing to glaucoma at lower intraocular pressures.