Mutations in nyx, encoding the leucine-rich proteoglycan nyctalopin, cause x-linked complete congenital stationary night blindness

ABSTRACT During development, visual photoreceptors, bipolar cells and other neurons establish connections within the retina enabling the eye to process visual images over approximately 7 log

units of illumination1. Within the retina, cells that respond to light increment and light decrement are separated into ON- and OFF-pathways. Hereditary diseases are known to disturb these

retinal pathways, causing either progressive degeneration or stationary deficits2. Congenital stationary night blindness (CSNB) is a group of stable retinal disorders that are characterized

by abnormal night vision. Genetic subtypes of CSNB have been defined and different disease actions have been postulated3,4,5. The molecular bases have been elucidated in several subtypes,

providing a better understanding of the disease mechanisms and developmental retinal neurobiology2. Here we have studied 22 families with 'complete' X-linked CSNB (CSNB1; MIM

310500; ref. 4) in which affected males have night blindness, some photopic vision loss and a defect of the ON-pathway. We have found 14 different mutations, including 1 founder mutation in

7 families from the United States, in a novel candidate gene, _NYX_. _NYX_, which encodes a glycosylphosphatidyl (GPI)-anchored protein called nyctalopin, is a new and unique member of the

small leucine-rich proteoglycan (SLRP) family6. The role of other SLRP proteins suggests that mutant nyctalopin disrupts developing retinal interconnections involving the ON-bipolar cells,

leading to the visual losses seen in patients with complete CSNB. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution

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families for participation; K. Boycott, J. Friedman, D. Rancourt, S. Robbins, P. Schnetkamp, W. Stell, M. Walter and R. Winkfein for discussions; and J. Whitehead, D. Martindale and L. Yong

for technical assistance. This research was supported in part by operating grants to N.T.B.-H. from the RP Research Foundation (Foundation Fighting Blindness), the Medical Research Council

of Canada, and the I.D. Bebensee Foundation, and from the Foundation Fighting Blindness to D.G.B., S.G.J. and R.G.W. In addition, R.G.W. was supported by an unrestricted grant from Research

to Prevent Blindness, S.G.J. by NIH grant EY-05627 and D.G.B. by NIH grant EY05235. N.T.B.-H. was also supported by the Roy Allen Endowment, The Alberta Children's Hospital Foundation

and the Department of Ophthalmology, University of Alberta (W.G. Pearce and I.M. MacDonald). AUTHOR INFORMATION Author notes * Margaret J. Naylor and Tracy A. Maybaum: These authors

contributed equally to this work. AUTHORS AND AFFILIATIONS * Department of Medical Genetics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada N.Torben Bech-Hansen, 

Margaret J. Naylor, Tracy A. Maybaum & Rebecca L. Sparkes * Department of Biology, and Centre for Environmental Research, University of Victoria, Victoria, British Columbia, Canada Ben

Koop * Retina Foundation of the Southwest, Dallas, Texas, USA David G. Birch * The Netherlands Ophthalmic Research Institute, Amsterdam, The Netherlands Arthur A.B. Bergen * Department of

Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada Clemens F.M. Prinsen * Department of Ophthalmology, Children's Hospital, and McGill University, Montreal,

Quebec, Canada Robert C. Polomeno * Institut fur Humangenetik, Universitats-Klinikum Hamburg-Eppendorf, Hamburg, Germany Andreas Gal * Department of Ophthalmology, Emory Eye Center, Atlanta,

Georgia, USA Arlene V. Drack * Department of Ophthalmology, SUNY Downstate, Brooklyn Medical Center, Brooklyn, New York Maria A. Musarella * Scheie Eye Institute, University of

Pennsylvania, Philadelphia, Pennsylvania, USA Samuel G. Jacobson * Department of Ophthalmology and Visual Sciences, Texas Tech University Health Sciences Center, Lubbock, Texas, USA

Rockefeller S.L. Young * Casey Eye Institute, Oregon Health Sciences University, Portland, Oregon, USA Richard G. Weleber Authors * N.Torben Bech-Hansen View author publications You can also

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Scholar CORRESPONDING AUTHOR Correspondence to N.Torben Bech-Hansen. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Bech-Hansen, N., Naylor, M.,

Maybaum, T. _et al._ Mutations in _NYX_, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness. _Nat Genet_ 26, 319–323 (2000).

https://doi.org/10.1038/81619 Download citation * Received: 17 April 2000 * Accepted: 10 August 2000 * Issue Date: November 2000 * DOI: https://doi.org/10.1038/81619 SHARE THIS ARTICLE

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