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

journal contribution
posted on 2023-05-18, 06:55 authored by Awadalla, MS, Fingert, JH, Roos, BE, Chen, S, Holmes, R, Graham, SL, Chehade, M, Galanopolous, A, Ridge, B, Souzeau, E, Zhou, T, Siggs, OM, Alexander HewittAlexander Hewitt, Mackey, DA, Kathryn BurdonKathryn Burdon, Craig, JE

Purpose: To investigate the presence of TBK1 copy number variations in a large, well-characterized Australian cohort of patients with glaucoma comprising both normal-tension glaucoma and high-tension glaucoma cases.

Design: A retrospective cohort study.

Methods: DNA samples from patients with normal-tension glaucoma and high-tension glaucoma and unaffected controls were screened for TBK1 copy number variations using real-time quantitative polymerase chain reaction. Samples with additional copies of the TBK1 gene were further tested using custom comparative genomic hybridization arrays.

Results: Four out of 334 normal-tension glaucoma cases (1.2%) were found to carry TBK1 copy number variations using quantitative polymerase chain reaction. One extra dose of the TBK1 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 TBK1 copy number variation segregated with normal-tension glaucoma in the family members of the probands, showing an autosomal dominant pattern of inheritance. No TBK1 copy number variations were detected in 1045 Australian patients with high-tension glaucoma or in 254 unaffected controls.

Conclusion: We report the presence of TBK1 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 TBK1 to be an important cause of normal-tension glaucoma, but do not suggest common involvement in high-tension glaucoma.


Publication title

American Journal of Ophthalmology








Menzies Institute for Medical Research


Elsevier Science Inc

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? Copyright 2015 BY ELSEVIER INC.

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Clinical health not elsewhere classified

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