Copy number variations of TBK1 in Australian patients with primary open-angle glaucoma

<p><strong>Purpose:</strong> To investigate the presence of <i>TBK1</i> copy number variations in a large, well-characterized Australian cohort of patients with glaucoma comprising both normal-tension glaucoma and high-tension glaucoma cases.</p> <p><strong>Design:</strong> A retrospective cohort study.</p> <p><strong>Methods:</strong> DNA samples from patients with normal-tension glaucoma and high-tension glaucoma and unaffected controls were screened for <i>TBK1</i> copy number variations using real-time quantitative polymerase chain reaction. Samples with additional copies of the <i>TBK1</i> gene were further tested using custom comparative genomic hybridization arrays.</p> <p><strong>Results:</strong> Four out of 334 normal-tension glaucoma cases (1.2%) were found to carry <i>TBK1</i> copy number variations using quantitative polymerase chain reaction. One extra dose of the <i>TBK1</i> gene (duplication) was detected in 3 normal-tension glaucoma patients, while 2 extra doses of the gene (triplication) were detected in a fourth normal-tension glaucoma patient. The results were further confirmed by custom comparative genomic hybridization arrays. Further, the <i>TBK1</i> copy number variation segregated with normal-tension glaucoma in the family members of the probands, showing an autosomal dominant pattern of inheritance. No <i>TBK1</i> copy number variations were detected in 1045 Australian patients with high-tension glaucoma or in 254 unaffected controls.</p> <p><strong>Conclusion:</strong> We report the presence of <i>TBK1</i> copy number variations in our Australian normal-tension glaucoma cohort, including the first example of more than 1 extra copy of this gene in glaucoma patients (gene triplication). These results confirm <i>TBK1</i> to be an important cause of normal-tension glaucoma, but do not suggest common involvement in high-tension glaucoma.</p>