ABCA4 Variations in Patients with Bull's-eye Maculopathy

Abstract

Abstract: : Purpose: To evaluate the coding sequences of the ABCA4 gene in a cohort of patients with bull's-eye maculopathy. Methods: Bull's-eye maculopathy is characterized by a contiguous ring of atrophic pigment epithelium or pigment epithelium mottling surrounding a central spared region. Phenotypic variations in forty-seven patients, including six sibling pairs, with bull's-eye maculopathy have been previously reported. Electrodiagnostic testing classified patients as having macular dystrophy (MD), cone-rod dystrophy (CRD), rod-cone dystrophy (RCD), or cone dystrophy (CD). For this study, blood samples from each patient were used to prepare genomic DNA. The entire coding sequence of the ABCA4 gene of each patient was then screened for sequence variations using single-stranded conformational polymorphism analysis (SSCP) followed by automated DNA sequencing. Results: Thirteen patients (28%) were found to have a potential disease-causing sequence change on at least on allele. Of these, nine had MD, three had CRD, and one had RCD. Three patients harbored a Gly1961Glu variation, the most common ABCA4 change in patients with Stargardt disease. Of these three, two had MD and a second ABCA4 base change, Cys1490Tyr or Asn905Ser, which has also been associated with Stargardt disease. The remaining patient with a Gly1961Glu variation had CRD and no other detected base changes. The second most common Stargardt ABCA4 change, Ala1038Val, was seen in one patient with CRD. One patient with MD had a Leu1201Arg change, which has been associated with CRD. Five previously unreported variations were seen in four different exons. Conclusions: Variations in the ABCA4 gene are common in bull's-eye maculopathy. ABCA4 changes can be seen in macular dystrophy, cone-rod dystrophy, and rod-cone dystrophy. The same ABCA4 variation may be associated with the clinically distinct entities of Stargardt disease and bull's-eye maculopathy.

Keywords: retinal degenerations: hereditary • molecular biology