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Am J Ophthalmol. 2015 Jan;159(1):124-30.e1. doi: 10.1016/j.ajo.2014.09.044. Epub 2014 Oct 2.

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

Author information

1
Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia. Electronic address: mona.awadalla@flinders.edu.au.
2
Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa; Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa.
3
Vitreoretinal Unit, Vision Eye Institute, Sydney, Australia.
4
Palmerston North Hospital, Palmerston North, New Zealand.
5
Australian School of Advanced Medicine, Macquarie University, Sydney, Australia.
6
South Australian Institute of Ophthalmology, Royal Adelaide Hospital, Adelaide, Australia.
7
Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia.
8
Lions Eye Institute, Perth, Australia.
9
Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia; Menzies Research Institute Tasmania, University of Tasmania, Hobart, Australia.

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.

PMID:
25284765
PMCID:
PMC4355400
DOI:
10.1016/j.ajo.2014.09.044
[Indexed for MEDLINE]
Free PMC Article

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