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

N. Torben Bech-Hansen, Margaret J. Naylor, Tracy A. Maybaum, Rebecca L. Sparkes, Ben Koop, David G. Birch, Arthur A B Bergen, Clemens F M Prinsen, Robert C. Polomeno, Andreas Gal, Arlene V. Drack, Maria A. Musarella, Samuel G. Jacobson, Rockefeller S L Young, Richard Weleber

Research output: Contribution to journalArticle

234 Citations (Scopus)

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 postulated3-5. 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.

Original languageEnglish (US)
Pages (from-to)319-323
Number of pages5
JournalNature Genetics
Volume26
Issue number3
DOIs
StatePublished - 2000

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Proteoglycans
Leucine
Mutation
Retina
Night Vision
Night Blindness
Light
Color Vision
Photoreceptor Cells
Inborn Genetic Diseases
Mutant Proteins
Neurons
Congenital stationary night blindness
Genes
Proteins
Small Leucine-Rich Proteoglycans

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Mutations in NYX, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness. / Bech-Hansen, N. Torben; Naylor, Margaret J.; Maybaum, Tracy A.; Sparkes, Rebecca L.; Koop, Ben; Birch, David G.; Bergen, Arthur A B; Prinsen, Clemens F M; Polomeno, Robert C.; Gal, Andreas; Drack, Arlene V.; Musarella, Maria A.; Jacobson, Samuel G.; Young, Rockefeller S L; Weleber, Richard.

In: Nature Genetics, Vol. 26, No. 3, 2000, p. 319-323.

Research output: Contribution to journalArticle

Bech-Hansen, NT, Naylor, MJ, Maybaum, TA, Sparkes, RL, Koop, B, Birch, DG, Bergen, AAB, Prinsen, CFM, Polomeno, RC, Gal, A, Drack, AV, Musarella, MA, Jacobson, SG, Young, RSL & Weleber, R 2000, 'Mutations in NYX, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness', Nature Genetics, vol. 26, no. 3, pp. 319-323. https://doi.org/10.1038/81619
Bech-Hansen, N. Torben ; Naylor, Margaret J. ; Maybaum, Tracy A. ; Sparkes, Rebecca L. ; Koop, Ben ; Birch, David G. ; Bergen, Arthur A B ; Prinsen, Clemens F M ; Polomeno, Robert C. ; Gal, Andreas ; Drack, Arlene V. ; Musarella, Maria A. ; Jacobson, Samuel G. ; Young, Rockefeller S L ; Weleber, Richard. / Mutations in NYX, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness. In: Nature Genetics. 2000 ; Vol. 26, No. 3. pp. 319-323.
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AU - Sparkes, Rebecca L.

AU - Koop, Ben

AU - Birch, David G.

AU - Bergen, Arthur A B

AU - Prinsen, Clemens F M

AU - Polomeno, Robert C.

AU - Gal, Andreas

AU - Drack, Arlene V.

AU - Musarella, Maria A.

AU - Jacobson, Samuel G.

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AU - Weleber, Richard

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