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Gerald A. Fishman, MD; Edwin M. Stone, MD, PhD; David A. Eliason, BA; Chris M. Taylor, BS; Martin Lindeman, COMT; Deborah J. Derlacki, BA

Arch Ophthalmol. 2003;121:851-855.

Objective  To identify sequence variations in the ABCA4 gene in a cohort of patients with autosomal recessive cone-rod dystrophy.

Methods  The coding sequences of the ABCA4 gene were analyzed in 30 unrelated probands. In those patients with plausible disease-causing variations, correlations were made between genotype and fundus phenotype as well as with electrophysiological and visual field findings.

Results  Sixteen (53%) of 30 probands were found to harbor plausible disease-causing variations in the ABCA4 gene. Two distinctly different fundus phenotypes were observed in our cohort of patients. Twelve patients showed diffuse pigmentary degenerative changes, whereas 4 showed either no pigmentary changes or only a mild degree of peripheral pigment degeneration. An associa-tion between certain sequence variations and each of these 2 different phenotypes was observed.

Conclusions  Our findings confirm that a substantial percentage of patients with autosomal recessive cone-rod dystrophy are likely to harbor a mutation in the ABCA4 gene as the cause of their disease. The fundus phenotype observed in such patients is quite variable, and certain fundus phenotypes may be more associated with certain genotypes.

Clinical Relevance  Identification of the molecular genetic basis for various inherited human retinal dystrophies, such as cone-rod dystrophy, facilitates a potentially better understanding of the mechanisms by which photoreceptor cells degenerate. This in turn provides guidance as to how to better proceed in identifying the most optimal future therapeutic strategies.

From the Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago (Dr Fishman, Mr Lindeman, and Ms Derlacki); and the Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City (Dr Stone, Mr Eliason, and Ms Taylor). The authors have no relevant financial interest in this article.

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