Copy Number Variations of TBK1 in Australian Patients With Primary Open-Angle Glaucoma

被引：63

作者：

Awadalla, Mona S. ^{[1
]}

Fingert, John H. ^{[2
,3
]}

Roos, Benjamin E. ^{[2
,3
]}

Chen, Simon ^{[4
]}

Holmes, Richard ^{[5
]}

Graham, Stuart L. ^{[6
]}

Chehade, Mark ^{[7
]}

Galanopolous, Anna ^{[7
]}

Ridge, Bronwyn ^{[1
]}

Souzeau, Emmanuelle ^{[1
]}

Zhou, Tiger ^{[1
]}

Siggs, Owen M. ^{[1
]}

Hewitt, Alex W. ^{[8
]}

Mackey, David A. ^{[8
]}

Burdon, Kathryn P. ^{[1
,9
]}

Craig, Jamie E. ^{[1
]}

机构：

[1] Flinders Univ S Australia, Flinders Med Ctr, Dept Ophthalmol, Adelaide, SA 5001, Australia

[2] Univ Iowa, Carver Coll Med, Dept Ophthalmol & Visual Sci, Iowa City, IA USA

[3] Univ Iowa, Carver Coll Med, Stephen Wynn Inst Vis Res, Iowa City, IA USA

[4] Vis Eye Inst, Vitreoretinal Unit, Sydney, NSW, Australia

[5] Palmerston N Hosp, Palmerston North, New Zealand

[6] Macquarie Univ, Australian Sch Adv Med, Sydney, NSW 2109, Australia

[7] Royal Adelaide Hosp, South Australian Inst Ophthalmol, Adelaide, SA 5000, Australia

[8] Lions Eye Inst, Perth, WA, Australia

[9] Univ Tasmania, Menzies Res Inst Tasmania, Hobart, Tas, Australia

来源：

AMERICAN JOURNAL OF OPHTHALMOLOGY | 2015年 / 159卷 / 01期

基金：

英国医学研究理事会;

关键词：

NORMAL-TENSION GLAUCOMA; OPTINEURIN; ASSOCIATION; GENE; SUSCEPTIBILITY; DUPLICATION; PREVALENCE; MUTATIONS; AUTOPHAGY;

D O I：

10.1016/j.ajo.2014.09.044

中图分类号：

R77 [眼科学];

学科分类号：

100212 ;

摘要：

center dot 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. center dot DESIGN: A retrospective cohort study. center dot 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. center dot 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. center dot 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. (C) 2015 by Elsevier Inc. All rights reserved.

引用

页码：124 / 130

页数：7

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