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A Novel Missense Mutation in Both OPN1LW and OPN1MW Cone Opsin Genes Causes X-Linked Cone Dystrophy (XLCOD5)

  • Jessica C. Gardner
  • Tom R. Webb
  • Naheed Kanuga
  • Anthony G. Robson
  • Graham E. Holder
  • Andrew Stockman
  • Caterina Ripamonti
  • Neil D. Ebenezer
  • Olufunmilola Ogun
  • Sophie Devery
  • Genevieve A. Wright
  • Eamonn R. Maher
  • Michael E. Cheetham
  • Anthony T. Moore
  • Michel MichaelidesEmail author
  • Alison J. HardcastleEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 723)

Abstract

X-linked cone and cone-rod dystrophies (XLCOD and XLCORD) are an inherited group of retinal disorders primarily involving cone photoreceptors. The most common cause is mutation of RPGR. In a British family with XLCOD, we mapped the disorder to Xq26.1-qter, excluding RPGR and other known retinal degeneration genes. The cone opsin gene array on Xq28 was a positional candidate locus. A novel missense mutation (c.529T > C; p.W177R) was identified in exon 3 of both the long wavelength-sensitive (OPN1LW; LW, red) and medium wavelength-sensitive (OPN1MW; MW, green) cone opsin genes, which segregated with disease. Exon 3 sequences of both genes were identical, derived from the OPN1MW gene by partial gene conversion. The amino acid W177 is conserved in all opsins across species. We have shown that W177R in MW opsin results in protein misfolding and retention in the endoplasmic reticulum (ER). Mutations in the OPN1LW /OPN1MW cone opsin gene array can therefore cause a spectrum of phenotypes, from colour blindness to progressive cone dystrophy (XLCOD5).

Keywords

Cone opsin Cone dystrophy X-linked XLCOD5 Opsin array 

Notes

Acknowledgements

This research was supported by funding from Fight for Sight UK, The British Retinitis Pigmentosa Society, Wellcome Trust, Moorfields Special Trustees and the National Institute for Health Research UK to the Biomedical Research Centre for Ophthalmology Michel Michaelides is supported by an FFB Career Development Award.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Jessica C. Gardner
    • 1
  • Tom R. Webb
    • 1
  • Naheed Kanuga
    • 1
  • Anthony G. Robson
    • 1
    • 2
  • Graham E. Holder
    • 1
    • 2
  • Andrew Stockman
    • 1
  • Caterina Ripamonti
    • 1
  • Neil D. Ebenezer
    • 1
  • Olufunmilola Ogun
    • 1
  • Sophie Devery
    • 2
  • Genevieve A. Wright
    • 2
  • Eamonn R. Maher
    • 3
  • Michael E. Cheetham
    • 1
  • Anthony T. Moore
    • 1
    • 2
  • Michel Michaelides
    • 1
    • 2
    Email author
  • Alison J. Hardcastle
    • 1
    Email author
  1. 1.UCL Institute of OphthalmologyLondonUK
  2. 2.Moorfields Eye HospitalLondonUK
  3. 3.West Midlands Regional Genetics ServiceBirmingham Women’s HospitalBirminghamUK

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