TBK1 gene duplication and normal-tension glaucoma.
OBJECTIVE
Normal-tension glaucoma (NTG) is a common cause of vision loss.


OBJECTIVE
To investigate the role of TANK binding kinase 1 (TBK1) gene duplications in NTG to gain insights into the causes of glaucoma that occurs at low intraocular pressure (IOP).


METHODS
In this multicenter case-control study, we investigated patients who met the criteria for NTG, including glaucomatous optic neuropathy, visual field defects, and maximum recorded untreated IOP of 21 mm Hg or less, and matched controls. Participants (N = 755) were recruited from Southampton, United Kingdom (180 patients and 178 controls), Rochester, Minnesota (65 patients and 12 controls), New York, New York (96 patients and 16 controls), and Iowa City, Iowa (208 controls).


METHODS
Detection of TBK1 gene duplications and comparison of the extent of the identified DNA that is duplicated with prior TBK1 copy number variations associated with NTG.


RESULTS
A TBK1 gene duplication was detected in 1 of 96 patients (1.0%) from New York and none of the controls. Analysis of duplication borders with comparative genome hybridization demonstrated that this patient has a novel duplication that has not been previously reported. No gene duplications were detected in any of the other cohorts of patients or controls.


CONCLUSIONS
Duplication of the TBK1 gene is a rare cause of NTG. The identification of another case of NTG attributed to TBK1 gene duplication strengthens the case that this mutation causes glaucoma.
Einhorn Clinical Research Center, New York Eye and Ear Infirmary, New York.
Robert
R
Ritch
Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City3Institute for Vision Research, University of Iowa, Iowa City.
Ben
B
Darbro
Department of Ophthalmology, Frimley Part Hospital, Surrey, United Kingdom.
Geeta
G
Menon
Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota.
Cheryl L
CL
Khanna
Institute for Vision Research, University of Iowa, Iowa City6Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City.
Frances
F
Solivan-Timpe
Institute for Vision Research, University of Iowa, Iowa City6Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City.
Ben R
BR
Roos
Department of Surgery, University of Connecticut Health Center, Farmington.
Mansoor
M
Sarfarzi
Department of Ophthalmology, Gifu University Graduate School of Medicine, Gifu, Japan.
Kazuhide
K
Kawase
Department of Ophthalmology, Gifu University Graduate School of Medicine, Gifu, Japan.
Tetsuya
T
Yamamoto
Department of Ophthalmology, Johns Hopkins University, Baltimore, Maryland10Department of International Health, Johns Hopkins University, Baltimore, Maryland11Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.
Alan L
AL
Robin
Southampton Eye Unit, Southampton General Hospital, Southampton, United Kingdom.
Andrew J
AJ
Lotery
Institute for Vision Research, University of Iowa, Iowa City6Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City.
John H
JH
Fingert
D000368:Aged; D004247:DNA / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020440:Gene Duplication; D020022:Genetic Predisposition to Disease; D006801:Humans; D007429:Intraocular Pressure / Q000502:physiology*; D057066:Low Tension Glaucoma / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies
D004247:DNA; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human