Awadalla, MS and Fingert, JH and Roos, BE and Chen, S and Holmes, R and Graham, SL and Chehade, M and Galanopolous, A and Ridge, B and Souzeau, E and Zhou, T and Siggs, OM and Hewitt, AW and Mackey, DA and Burdon, KP and Craig, JE, Copy number variations of TBK1 in Australian patients with primary open-angle glaucoma, American Journal of Ophthalmology, 159, (1) pp. 124-130. ISSN 0002-9394 (2015) [Refereed Article]
Copyright 2015 BY ELSEVIER INC.
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.
|Item Type:||Refereed Article|
|Keywords:||glaucoma, genetics, CNV|
|Research Division:||Medical and Health Sciences|
|Research Group:||Ophthalmology and Optometry|
|Objective Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Objective Field:||Hearing, Vision, Speech and Their Disorders|
|Author:||Hewitt, AW (Professor Alex Hewitt)|
|Author:||Burdon, KP (Associate Professor Kathryn Burdon)|
|Web of Science® Times Cited:||20|
|Deposited By:||Menzies Institute for Medical Research|
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