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

Citation

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 Statement

 Copyright 2015 BY ELSEVIER INC.

DOI: doi:10.1016/j.ajo.2014.09.044

Abstract

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 Details

Item Type:Refereed Article
Keywords:glaucoma, genetics, CNV
Research Division:Medical and Health Sciences
Research Group:Ophthalmology and Optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Hearing, Vision, Speech and Their Disorders
Author:Hewitt, AW (Dr Alex Hewitt)
Author:Burdon, KP (Associate Professor Kathryn Burdon)
ID Code:98082
Year Published:2015
Web of Science® Times Cited:18
Deposited By:Menzies Institute for Medical Research
Deposited On:2015-02-02
Last Modified:2016-02-09
Downloads:0

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