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Electroretinographic Abnormalities in Parents of Patients With Leber Congenital Amaurosis Who Have Heterozygous GUCY2D Mutations
Robert K. Koenekoop, MD, PhD;
Gerald A. Fishman, MD;
Alessandro Iannaccone, MD;
Hany Ezzeldin, PhD;
Maria L. Ciccarelli, COMT, CO;
Alfonso Baldi, MD;
Janet S. Sunness, MD;
Andrew J. Lotery, MD;
Monica M. Jablonski, PhD;
Steven J. Pittler, PhD;
Irene Maumenee, MD
Arch Ophthalmol. 2002;120:1325-1330.
Background Leber congenital amaurosis (LCA) is an infrequently encountered congenital
form of retinitis pigmentosa with marked genetic and clinical heterogeneity.
Thus far, 10 genes have been identified in this disorder since 1996. In the
future, LCA may become treatable by gene and/or pharmacological intervention,
and these therapies will likely be gene specific, giving major significance
to rapid gene identification and gene-phenotype studies.
Objective To test the hypothesis that parents of patients with LCA have identifiable
electroretinographic and psychophysical changes.
Subjects, Materials, and Methods Complete eye examinations and electroretinographic studies were performed
on 2 sets of parents whose offspring were diagnosed as having LCA and who
were found to carry a mutation in 1 of the 10 LCA genes—GUCY2D. One set of parents also underwent static perimetry threshold
measurements.
Results We found that single flash-light–adapted a- and b-wave amplitudes,
30-Hz flicker, or both cone signals were significantly decreased in amplitude
in 4 heterozygotes, while 2 parents showed delayed 30-Hz flicker implicit
times. Electroretinographic rod-mediated signals were normal in 2 of the heterozygotes,
but subnormal in 2. Static perimetry testing showed normal thresholds in the
2 heterozygotes tested.
Main Outcome Measures Single flash-light–adapted a- and b-wave amplitudes and implicit
times, 30- or 32-Hz flicker amplitudes and implicit times, rod-mediated signals,
and dark-adapted, rod-mediated thresholds.
Conclusions Some carrier parents of patients with LCA and a GUCY2D mutation develop measurable, cone and possibly rod abnormalities most
consistent with a mild cone-rod dysfunction. This correlates well with the
known retinal expression pattern of GUCY2D, which
is considerably higher in cone compared with rod photoreceptor cells.
From the McGill Ocular Genetics Laboratory, Montreal Children's Hospital,
McGill University, Montreal, Quebec (Dr Koenekoop); Department of Ophthalmology,
University of Illinois at Chicago (Dr Fishman); Retinal Degeneration Research
Center, University of Tennessee Health Sciences Center, Memphis (Drs Iannaccone
and Jablonski); Vision Science Research Center, University of Alabama, Birmingham
(Drs Ezzeldin and Pittler); Division of Ophthalmology, Fatebenefratelli Hospital
(Ms Ciccarelli), and the Regina Elena Institute (Dr Baldi), Rome, Italy; Lions
Vision Center of the Wilmer Eye Institute (Dr Sunness), and The Johns Hopkins
Center for Hereditary Eye Diseases (Dr Maumenee), The Johns Hopkins University,
Baltimore, Md; and the Department of Ophthalmology, University of Iowa, Iowa
City (Dr Lotery).
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