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

Mona S Awadalla; John H Fingert; Benjamin E Roos; Simon Chen; Richard Holmes; Stuart L Graham; Mark Chehade; Anna Galanopolous; Bronwyn Ridge; Emmanuelle Souzeau; Tiger Zhou; Owen M Siggs; Alex W Hewitt; David A Mackey; Kathryn P Burdon; Jamie E Craig

doi:10.1016/j.ajo.2014.09.044

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

Journal article

Open access

Peer reviewed

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

Mona S Awadalla, John H Fingert, Benjamin E Roos, Simon Chen, Richard Holmes, Stuart L Graham, Mark Chehade, Anna Galanopolous, Bronwyn Ridge, Emmanuelle Souzeau, …

American journal of ophthalmology, Vol.159(1), pp.124-130.e1

01/2015

DOI: 10.1016/j.ajo.2014.09.044

PMCID: PMC4355400

PMID: 25284765

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Abstract

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. A retrospective cohort study. 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. 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. 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.

Mutation

Australia

Glaucoma, Open-Angle - genetics

Humans

Middle Aged

Protein-Serine-Threonine Kinases - genetics

Male

DNA Copy Number Variations - genetics

Case-Control Studies

Comparative Genomic Hybridization

Pedigree

Adult

Female

Aged

Retrospective Studies

Real-Time Polymerase Chain Reaction

Details

Title: Subtitle: Copy number variations of TBK1 in Australian patients with primary open-angle glaucoma
Creators: Mona S Awadalla - Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia. Electronic address: mona.awadalla@flinders.edu.au
John H Fingert - 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
Benjamin E Roos - 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
Simon Chen - Vitreoretinal Unit, Vision Eye Institute, Sydney, Australia
Richard Holmes - Palmerston North Hospital, Palmerston North, New Zealand
Stuart L Graham - Australian School of Advanced Medicine, Macquarie University, Sydney, Australia
Mark Chehade - South Australian Institute of Ophthalmology, Royal Adelaide Hospital, Adelaide, Australia
Anna Galanopolous - South Australian Institute of Ophthalmology, Royal Adelaide Hospital, Adelaide, Australia
Bronwyn Ridge - Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia
Emmanuelle Souzeau - Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia
Tiger Zhou - Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia
Owen M Siggs - Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia
Alex W Hewitt - Lions Eye Institute, Perth, Australia
David A Mackey - Lions Eye Institute, Perth, Australia
Kathryn P Burdon - Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia; Menzies Research Institute Tasmania, University of Tasmania, Hobart, Australia
Jamie E Craig - Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia
Resource Type: Journal article
Publication Details: American journal of ophthalmology, Vol.159(1), pp.124-130.e1
DOI: 10.1016/j.ajo.2014.09.044
PMID: 25284765
PMCID: PMC4355400
NLM abbreviation: Am J Ophthalmol
ISSN: 1879-1891
eISSN: 1879-1891
Publisher: United States
Grant note: R01 EY023512 / NEI NIH HHS R01 EY018825 / NEI NIH HHS NEI EY018825 / NEI NIH HHS EY023512 / NEI NIH HHS
Language: English
Date published: 01/2015
Academic Unit: Ophthalmology and Visual Sciences
Record Identifier: 9983979977802771

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