Adult-Onset Primary Open-Angle Glaucoma Caused by Mutations in Optineurin

American Association for the Advancement of Science (AAAS) - Tập 295 Số 5557 - Trang 1077-1079 - 2002
Tayebeh Rezaie1, Anne H. Child2,3, Roger A. Hitchings3, Glen Brice2,3, Lauri Miller4, Miguel Coca‐Prados5, Elise Héon6, Theodore Krupin7, Robert Ritch8, Donald L. Kreutzer4, Ronald P. Crick9, Mansoor Sarfarazi1
1Molecular Ophthalmic Genetics Laboratory, Surgical Research Center, Department of Surgery, University of Connecticut Health Center, Farmington, CT 06030, USA.
2Department of Cardiological Sciences, St. George's Hospital Medical School, London, SW17 0RE, UK.
3Glaucoma Research Unit, Moorfields Eye Hospital, London, ECIV 2PD, UK.
4Department of Pathology, University of Connecticut Health Center, Farmington, CT 06030, USA
5Department of Ophthalmology and Visual Science, Yale University, New Haven, CT 06520, USA.
6Department of Ophthalmology, Vision Research Program UHN, Toronto, Canada M5T 2S8.
7University Eye Specialists, 676 North St. Clair, Suite 320, Chicago, IL 60611, USA.
8New York Eye and Ear Infirmary, and New York Medical College, Valhalla, NY 10003, USA.
9International Glaucoma Association, 108C Warner Road, London, SE5 9HQ, UK.

Tóm tắt

Primary open-angle glaucoma (POAG) affects 33 million individuals worldwide and is a leading cause of blindness. In a study of 54 families with autosomal dominantly inherited adult-onset POAG, we identified the causative gene on chromosome 10p14 and designated it OPTN (for “optineurin”). Sequence alterations in OPTN were found in 16.7% of families with hereditary POAG, including individuals with normal intraocular pressure. The OPTN gene codes for a conserved 66-kilodalton protein of unknown function that has been implicated in the tumor necrosis factor–α signaling pathway and that interacts with diverse proteins including Huntingtin, Ras-associated protein RAB8, and transcription factor IIIA. Optineurin is expressed in trabecular meshwork, nonpigmented ciliary epithelium, retina, and brain, and we speculate that it plays a neuroprotective role.

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Tài liệu tham khảo

10.1136/bjo.80.5.389

Quigley H. A., Vitale S., Invest. Ophthalmol. Vis. Sci. 38, 83 (1997).

J. M. Tielsch et al. JAMA 266 369 (1991).

10.1136/bjo.76.8.494

10.1097/00004397-199403430-00016

E. B. Werner in The Glaucomas R. Ritch M. B. Shields T. Krupin Eds. (Mosby St. Louis MO 1996) vol. 2 chap. 36.

10.1136/bjo.67.12.818

10.1093/hmg/6.10.1667

10.1093/hmg/6.4.641

I. Stoilov et al. Am. J. Hum. Genet. 62 573 (1998).

E. M. Stone et al. Science 275 668 (1997).

10.1128/MCB.18.3.1601

M. Sarfarazi et al. Am. J. Hum. Genet. 62 641 (1998).

10.1074/jbc.M001500200

P. W. Faber et al. Hum. Mol. Genet. 7 1463 (1998).

R. J. Moreland et al. Nucleic Acids Res. 28 1986 (2000).

10.1016/S0960-9822(00)00864-2

Supplementary Web material is available on Science Online at www.sciencemag.org/cgi/content/full/295/5557/1077/DC1.

T. Rezaie M. Sarfarazi unpublished data.

10.1002/1098-1136(200010)32:1<42::AID-GLIA40>3.0.CO;2-3

10.1523/JNEUROSCI.20-23-08693.2000

10.1007/s004390100505

We thank P. Kaufman J. Seeman J. Suchecki and T. Digiulio for aqueous humors and eye specimens and P. Reynolds for clinical evaluation and interpretation of patients' notes. M.S. is supported by grants from the National Eye Institute (EY-09947) the International Glaucoma Association (IGA-G249) and the University of Connecticut General Clinical Research Center (M01-RR-06192). A.C. is supported by Bluff Field Charitable Trust U.K. the International Glaucoma Association and St. George's Hospital Medical School and National Health Service Trust. G.B. is supported by the Royal National Institute for the Blind.

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American Association for the Advancement of Science (AAAS)

Tập 295 Số 5557

1077-1079

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