April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
Cone Mosaic Disruption Caused by L/M Opsin Mutations in Bornholm Eye Disease
Author Affiliations & Notes
  • Jay Neitz
    Univ of Washington, Seattle, Washington
  • Melissa Wagner-Schuman
    Medical College of Wisconsin, Milwaukee, Wisconsin
  • Alfredo Dubra
    Flaum Eye Institute, University of Rochester, Rochester, New York
  • Stacy A. Sjoberg
    Crosby Eye Clinic, Crosby, Minnesota
  • Anthony T. Moore
    Ophthalmology, Institute of Ophthalmology, London, United Kingdom
  • Terri L. Young
    Duke University Medical Center, Durham, North Carolina
  • Maureen Neitz
    Univ of Washington, Seattle, Washington
  • Joseph Carroll
    Medical College of Wisconsin, Milwaukee, Wisconsin
  • Michel Michaelides
    Moorfields Eye Hospital, London, United Kingdom
  • Footnotes
    Commercial Relationships  Jay Neitz, None; Melissa Wagner-Schuman, None; Alfredo Dubra, None; Stacy A. Sjoberg, None; Anthony T. Moore, None; Terri L. Young, None; Maureen Neitz, None; Joseph Carroll, None; Michel Michaelides, None
  • Footnotes
    Support  RPB, FFS, NIH, Moorfields Special Trustees and the National Institute for Health Research UK, NHS Foundation Trust & UCL Institute of Ophthalmology. AD holds a Burroughs Wellcome Fund Career Award
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 4896. doi:
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      Jay Neitz, Melissa Wagner-Schuman, Alfredo Dubra, Stacy A. Sjoberg, Anthony T. Moore, Terri L. Young, Maureen Neitz, Joseph Carroll, Michel Michaelides; Cone Mosaic Disruption Caused by L/M Opsin Mutations in Bornholm Eye Disease. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4896.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Bornholm Eye Disease (BED) is an X-linked cone dysfunction syndrome with myopia, astigmatism and optic nerve changes. The underlying gene mapped to Xq28, as do the L/M cone opsin genes. We found two combinations of amino acids at the polymorphic positions 153, 171, 174, 178, and 180 encoded by exon 3 of L/M opsin genes that cause cone dysfunction and are never seen in males with normal vision. These combinations, LIAVA and LVAVA, have consistently been found in opsin genes of BED patients. Another mutation, C203R, was found in one family with X-linked cone dysfunction. We investigated the affect of these mutations on the cone mosaics in BED patients.

Methods: : 7 protanopes from 3 families were recruited from previously reported pedigrees (Michaelides et al., 2005 Ophthal. 112:1448; Young et al., 2004 Arch Ophthal. 122:897). Cone mosaic images were obtained using an adaptive optics ophthalmoscope and/or an adaptive optics scanning laser ophthalmoscope. SD-OCT images were examined for retinal lamination and thickness.

Results: : Families with the mutations, LIAVA, LVAVA and C203R were examined. From ocular biometry, the predicted SER ranged from +1D to -11D. Photoreceptor mosaic images revealed significant but variable disruption, with cone density ranging from near normal to reduced by >75%. Retinal thickness was reduced to a variable degree, with some subjects having significant macular thinning and others having normal thickness. Of note, two brothers showed disparate retinal thickness topography and cone mosaic disruption, despite harboring the same mutation, LIAVA.

Conclusions: : There was a wide range of photoreceptor mosaic phenotypes. While LIAVA and LVAVA opsins always lead to dysfunction of cones that express them, the degree to which they lead to vision disorder depends on the relative number of cones expressing the aberrant pigment, and on whether the pigment is LVAVA or LIAVA. Michaelides et al. (2004 BJO 88:291) stated that in BED, other genetic factors "within which the primary disease causing mutation is expressed may determine the final phenotype". Our anatomical data indicate that these "other factors" include ones that affect L:M cone ratio, which is known to be highly variable.

Keywords: myopia • color pigments and opsins • genetics 

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