April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
The G1961E Mutant Allele in the Stargardt Disease Gene ABCA4 Causes Bull’s Eye Maculopathy
W. P. Cella; V. C. Greenstein; J. Zernant-Rajang; R. T. Smith; G. R. Barile; N.-K. Wang; J. Tosi; S. Chang; S. H. Tsang; R. Allikmets
Author Affiliations & Notes
  • W. P. Cella
    Ophthalmology,
    Edward S. Harkness Eye Institute, Columbia University, New York, New York
  • V. C. Greenstein
    Ophthalmology,
    Edward S. Harkness Eye Institute, Columbia University, New York, New York
    Ophthalmology, New York University, School of Medicine, New York, New York
  • J. Zernant-Rajang
    Ophthalmology,
    Edward S. Harkness Eye Institute, Columbia University, New York, New York
  • R. T. Smith
    Ophthalmology,
    Edward S. Harkness Eye Institute, Columbia University, New York, New York
  • G. R. Barile
    Ophthalmology,
    Edward S. Harkness Eye Institute, Columbia University, New York, New York
  • N.-K. Wang
    Ophthalmology,
    Edward S. Harkness Eye Institute, Columbia University, New York, New York
  • J. Tosi
    Ophthalmology,
    Edward S. Harkness Eye Institute, Columbia University, New York, New York
  • S. Chang
    Ophthalmology,
    Edward S. Harkness Eye Institute, Columbia University, New York, New York
  • S. H. Tsang
    Ophthalmology,
    Edward S. Harkness Eye Institute, Columbia University, New York, New York
  • R. Allikmets
    Ophthalmology,
    Pathology & Cell Biology,
    Edward S. Harkness Eye Institute, Columbia University, New York, New York
  • Footnotes
    Commercial Relationships  W.P. Cella, None; V.C. Greenstein, None; J. Zernant-Rajang, None; R.T. Smith, None; G.R. Barile, None; N.-K. Wang, None; J. Tosi, None; S. Chang, None; S.H. Tsang, None; R. Allikmets, None.
  • Footnotes
    Support  NIH Grant EY02115, NIH Grant EY013435, NIH Grant EY018213, Research to Prevent Blindness, Foundation Fighting Blindness, Schneeweiss Stargardt Fund, The Starr Foundation
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 4491. doi:
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      W. P. Cella, V. C. Greenstein, J. Zernant-Rajang, R. T. Smith, G. R. Barile, N.-K. Wang, J. Tosi, S. Chang, S. H. Tsang, R. Allikmets; The G1961E Mutant Allele in the Stargardt Disease Gene ABCA4 Causes Bull’s Eye Maculopathy. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4491.

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Abstract

Purpose: : To characterize the pathological and functional consequences of the G1961E mutant allele in the Stargardt disease gene ABCA4.

Methods: : Fifteen patients were enrolled in the study. All patients had at least one G1961E mutation. The following procedures were performed: a comprehensive ophthalmic examination, fundus autofluorescence imaging (FAF), full-field scotopic and photopic electroretinograms (ERGs) and pattern ERGs. In addition fundus tracking microperimetry, spectral-domain optical coherence tomography (SD-OCT), and fluorescein angiography were performed in selected cases. Genetic screening was performed using the ABCR500 micro-array that currently detects 496 distinct ABCA4 variants.

Results: : All patients (30 eyes) had normal full-field scotopic and photopic ERGs and abnormal PERGs. On FAF all eyes had bull’s eye maculopathy without retinal flecks. Of the 6 patients (12 eyes) examined with SD-OCT, horizontal mid-line scans showed that one had disorganization of photoreceptor outer segments in the fovea, 2 had outer nuclear layer thinning probably due to photoreceptor atrophy proximal to the foveal center, and 3 had additional retinal pigment epithelium atrophy. On microperimetry, 6 patients (12 eyes) had eccentric fixation superior to the fovea and 5 of these patients had an absolute scotoma in the foveal area. DNA analysis revealed that 3 patients were homozygous G1961E/G1961E and the rest were compound heterozygotes for G1961E and another ABCA4 mutation. The G1961E alleles in either homozygosity or heterozygosity were associated with anatomical and functional pathologies limited to the parafoveal region and with a trend to delayed onset of symptoms, relative to other manifestations of ABCA4 mutations.

Conclusions: : The G1961E allele contributes to localized macular changes rather than generalized retinal dysfunction, and is a cause of bull’s eye maculopathy in either the homozygous or heterozygous state. Genetic testing is imperative for precise diagnosis of the underlying maculopathy. Current non-invasive imaging techniques can be used to detect photoreceptor damage at the earliest clinical onset of the disease.

Keywords: degenerations/dystrophies • gene/expression • imaging/image analysis: clinical 
© 2009, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
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