John H Fingert1, Alan L Robin1, Todd E Scheetz1, Young H Kwon1, Jeffrey M Liebmann1, Robert Ritch1, Wallace L M Alward1. 1. Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa (Dr Fingert, Dr Scheetz, Dr Kwon, Dr Alward); the Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa (Dr Fingert, Dr Scheetz, Dr Kwon, Dr Alward); the Departments of Ophthalmology and International Health, School of Medicine and the Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland (Dr Robin); the Department of Ophthalmology, University of Maryland, Baltimore, Maryland (Dr Robin); Columbia University Medical Center, New York, New York (Dr Liebmann); the Einhorn Clinical Research Center, New York Eye and Ear Infirmary of Mount Sinai, New York, New York (Dr Ritch).
Abstract
PURPOSE: To investigate the role of TANK-binding kinase 1 (TBK1) gene copy-number variations (ie, gene duplications and triplications) in the pathophysiology of various open-angle glaucomas. METHODS: In previous studies, we discovered that copy-number variations in the TBK1 gene are associated with normal-tension glaucoma. Here, we investigated the prevalence of copy-number variations in cohorts of patients with other open-angle glaucomas-juvenile-onset open-angle glaucoma (n=30), pigmentary glaucoma (n=209), exfoliation glaucoma (n=225), and steroid-induced glaucoma (n=79)-using a quantitative polymerase chain reaction assay. RESULTS: No TBK1 gene copy-number variations were detected in patients with juvenile-onset open-angle glaucoma, pigmentary glaucoma, or steroid-induced glaucoma. A TBK1 gene duplication was detected in one (0.44%) of the 225 exfoliation glaucoma patients. CONCLUSIONS: TBK1 gene copy-number variations (gene duplications and triplications) have been previously associated with normal-tension glaucoma. An exploration of other open-angle glaucomas detected a TBK1 copy-number variation in a patient with exfoliation glaucoma, which is the first example of a TBK1 mutation in a glaucoma patient with a diagnosis other than normal-tension glaucoma. A broader phenotypic range may be associated with TBK1 copy-number variations, although mutations in this gene are most often detected in patients with normal-tension glaucoma.
PURPOSE: To investigate the role of TANK-binding kinase 1 (TBK1) gene copy-number variations (ie, gene duplications and triplications) in the pathophysiology of various open-angle glaucomas. METHODS: In previous studies, we discovered that copy-number variations in the TBK1 gene are associated with normal-tension glaucoma. Here, we investigated the prevalence of copy-number variations in cohorts of patients with other open-angle glaucomas-juvenile-onset open-angle glaucoma (n=30), pigmentary glaucoma (n=209), exfoliation glaucoma (n=225), and steroid-induced glaucoma (n=79)-using a quantitative polymerase chain reaction assay. RESULTS: No TBK1 gene copy-number variations were detected in patients with juvenile-onset open-angle glaucoma, pigmentary glaucoma, or steroid-induced glaucoma. A TBK1 gene duplication was detected in one (0.44%) of the 225 exfoliation glaucomapatients. CONCLUSIONS:TBK1 gene copy-number variations (gene duplications and triplications) have been previously associated with normal-tension glaucoma. An exploration of other open-angle glaucomas detected a TBK1 copy-number variation in a patient with exfoliation glaucoma, which is the first example of a TBK1 mutation in a glaucomapatient with a diagnosis other than normal-tension glaucoma. A broader phenotypic range may be associated with TBK1 copy-number variations, although mutations in this gene are most often detected in patients with normal-tension glaucoma.
Authors: John H Fingert; Alan L Robin; Jennifer L Stone; Ben R Roos; Lea K Davis; Todd E Scheetz; Steve R Bennett; Thomas H Wassink; Young H Kwon; Wallace L M Alward; Robert F Mullins; Val C Sheffield; Edwin M Stone Journal: Hum Mol Genet Date: 2011-03-29 Impact factor: 6.150
Authors: Francesca Pasutto; Kate E Keller; Nicole Weisschuh; Heinrich Sticht; John R Samples; Yong-Feng Yang; Matthias Zenkel; Ursula Schlötzer-Schrehardt; Christian Y Mardin; Paolo Frezzotti; Beth Edmunds; Patricia L Kramer; Eugen Gramer; André Reis; Ted S Acott; Mary K Wirtz Journal: Hum Mol Genet Date: 2011-12-08 Impact factor: 6.150
Authors: Tin Aung; Mineo Ozaki; Takanori Mizoguchi; R Rand Allingham; Zheng Li; Aravind Haripriya; Satoko Nakano; Steffen Uebe; Jeffrey M Harder; Anita S Y Chan; Mei Chin Lee; Kathryn P Burdon; Yury S Astakhov; Khaled K Abu-Amero; Juan C Zenteno; Yildirim Nilgün; Tomasz Zarnowski; Mohammad Pakravan; Leen Abu Safieh; Liyun Jia; Ya Xing Wang; Susan Williams; Daniela Paoli; Patricio G Schlottmann; Lulin Huang; Kar Seng Sim; Jia Nee Foo; Masakazu Nakano; Yoko Ikeda; Rajesh S Kumar; Morio Ueno; Shin-ichi Manabe; Ken Hayashi; Shigeyasu Kazama; Ryuichi Ideta; Yosai Mori; Kazunori Miyata; Kazuhisa Sugiyama; Tomomi Higashide; Etsuo Chihara; Kenji Inoue; Satoshi Ishiko; Akitoshi Yoshida; Masahide Yanagi; Yoshiaki Kiuchi; Makoto Aihara; Tsutomu Ohashi; Toshiya Sakurai; Takako Sugimoto; Hideki Chuman; Fumihiko Matsuda; Kenji Yamashiro; Norimoto Gotoh; Masahiro Miyake; Sergei Y Astakhov; Essam A Osman; Saleh A Al-Obeidan; Ohoud Owaidhah; Leyla Al-Jasim; Sami Al Shahwan; Rhys A Fogarty; Paul Leo; Yaz Yetkin; Çilingir Oğuz; Mozhgan Rezaei Kanavi; Afsaneh Nederi Beni; Shahin Yazdani; Evgeny L Akopov; Kai-Yee Toh; Gareth R Howell; Andrew C Orr; Yufen Goh; Wee Yang Meah; Su Qin Peh; Ewa Kosior-Jarecka; Urszula Lukasik; Mandy Krumbiegel; Eranga N Vithana; Tien Yin Wong; Yutao Liu; Allison E Ashley Koch; Pratap Challa; Robyn M Rautenbach; David A Mackey; Alex W Hewitt; Paul Mitchell; Jie Jin Wang; Ari Ziskind; Trevor Carmichael; Rangappa Ramakrishnan; Kalpana Narendran; Rangaraj Venkatesh; Saravanan Vijayan; Peiquan Zhao; Xueyi Chen; Dalia Guadarrama-Vallejo; Ching Yu Cheng; Shamira A Perera; Rahat Husain; Su-Ling Ho; Ulrich-Christoph Welge-Luessen; Christian Mardin; Ursula Schloetzer-Schrehardt; Axel M Hillmer; Stefan Herms; Susanne Moebus; Markus M Nöthen; Nicole Weisschuh; Rohit Shetty; Arkasubhra Ghosh; Yik Ying Teo; Matthew A Brown; Ignacio Lischinsky; Jonathan G Crowston; Michael Coote; Bowen Zhao; Jinghong Sang; Nihong Zhang; Qisheng You; Vera Vysochinskaya; Panayiota Founti; Anthoula Chatzikyriakidou; Alexandros Lambropoulos; Eleftherios Anastasopoulos; Anne L Coleman; M Roy Wilson; Douglas J Rhee; Jae Hee Kang; Inna May-Bolchakova; Steffen Heegaard; Kazuhiko Mori; Wallace L M Alward; Jost B Jonas; Liang Xu; Jeffrey M Liebmann; Balram Chowbay; Elke Schaeffeler; Matthias Schwab; Fabian Lerner; Ningli Wang; Zhenglin Yang; Paolo Frezzotti; Shigeru Kinoshita; John H Fingert; Masaru Inatani; Kei Tashiro; André Reis; Deepak P Edward; Louis R Pasquale; Toshiaki Kubota; Janey L Wiggs; Francesca Pasutto; Fotis Topouzis; Michael Dubina; Jamie E Craig; Nagahisa Yoshimura; Periasamy Sundaresan; Simon W M John; Robert Ritch; Michael A Hauser; Chiea-Chuen Khor Journal: Nat Genet Date: 2015-02-23 Impact factor: 38.330
Authors: Francesca Pasutto; Tomoya Matsumoto; Christian Y Mardin; Heinrich Sticht; Johann H Brandstätter; Karin Michels-Rautenstrauss; Nicole Weisschuh; Eugen Gramer; Wishal D Ramdas; Leonieke M E van Koolwijk; Caroline C W Klaver; Johannes R Vingerling; Bernhard H F Weber; Friedrich E Kruse; Bernd Rautenstrauss; Yves-Alain Barde; André Reis Journal: Am J Hum Genet Date: 2009-09-17 Impact factor: 11.025
Authors: Robert Ritch; Ben Darbro; Geeta Menon; Cheryl L Khanna; Frances Solivan-Timpe; Ben R Roos; Mansoor Sarfarzi; Kazuhide Kawase; Tetsuya Yamamoto; Alan L Robin; Andrew J Lotery; John H Fingert Journal: JAMA Ophthalmol Date: 2014-05 Impact factor: 7.389
Authors: Ryan Zukerman; Alon Harris; Alice Verticchio Vercellin; Brent Siesky; Louis R Pasquale; Thomas A Ciulla Journal: Genes (Basel) Date: 2020-12-31 Impact factor: 4.096