title: Copy number variations of TBK1 in Australian patients with primary open-angle glaucoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia. Electronic address: mona.awadalla@flinders.edu.au.
authors.forename: Mona S
authors.initials: MS
authors.lastname: Awadalla
authors.affiliation: 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.
authors.forename: John H
authors.initials: JH
authors.lastname: Fingert
authors.affiliation: 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.
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Roos
authors.affiliation: Vitreoretinal Unit, Vision Eye Institute, Sydney, Australia.
authors.forename: Simon
authors.initials: S
authors.lastname: Chen
authors.affiliation: Palmerston North Hospital, Palmerston North, New Zealand.
authors.forename: Richard
authors.initials: R
authors.lastname: Holmes
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, Sydney, Australia.
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Graham
authors.affiliation: South Australian Institute of Ophthalmology, Royal Adelaide Hospital, Adelaide, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Chehade
authors.affiliation: South Australian Institute of Ophthalmology, Royal Adelaide Hospital, Adelaide, Australia.
authors.forename: Anna
authors.initials: A
authors.lastname: Galanopolous
authors.affiliation: Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia.
authors.forename: Bronwyn
authors.initials: B
authors.lastname: Ridge
authors.affiliation: Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Souzeau
authors.affiliation: Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia.
authors.forename: Tiger
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia.
authors.forename: Owen M
authors.initials: OM
authors.lastname: Siggs
authors.affiliation: Lions Eye Institute, Perth, Australia.
authors.forename: Alex W
authors.initials: AW
authors.lastname: Hewitt
authors.affiliation: Lions Eye Institute, Perth, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Mackey
authors.affiliation: Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia; Menzies Research Institute Tasmania, University of Tasmania, Hobart, Australia.
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: Burdon
authors.affiliation: Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia.
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Craig
mesh_terms: D000328:Adult; D000368:Aged; D001315:Australia; D016022:Case-Control Studies; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies
chemical_list: D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human