Importance: Normal-tension glaucoma (NTG) is a common cause of vision loss.
Objective: To investigate the role of TANK binding kinase 1 (TBK1) gene duplications in NTG to gain insights into the causes of glaucoma that occurs at low intraocular pressure (IOP).
Design, setting, and participants: In this multicenter case-control study, we investigated patients who met the criteria for NTG, including glaucomatous optic neuropathy, visual field defects, and maximum recorded untreated IOP of 21 mm Hg or less, and matched controls. Participants (N = 755) were recruited from Southampton, United Kingdom (180 patients and 178 controls), Rochester, Minnesota (65 patients and 12 controls), New York, New York (96 patients and 16 controls), and Iowa City, Iowa (208 controls).
Main outcomes and measures: Detection of TBK1 gene duplications and comparison of the extent of the identified DNA that is duplicated with prior TBK1 copy number variations associated with NTG.
Results: A TBK1 gene duplication was detected in 1 of 96 patients (1.0%) from New York and none of the controls. Analysis of duplication borders with comparative genome hybridization demonstrated that this patient has a novel duplication that has not been previously reported. No gene duplications were detected in any of the other cohorts of patients or controls.
Conclusions and relevance: Duplication of the TBK1 gene is a rare cause of NTG. The identification of another case of NTG attributed to TBK1 gene duplication strengthens the case that this mutation causes glaucoma.