Analysis of the ABCR (ABCA4) gene in 4-aminoquinoline retinopathy: Is retinal toxicity by chloroquine and hydroxychloroquine related to Stargardt disease?

PURPOSE: To determine if mutations in ABCR (ABCA4) are associated with chlo roquine/hydroxychloroquine retinopathy, METHODS: DNA from eight patients with chloroquine or hydroxychloroquine ret inopathy was studied. Controls were 80 individuals over age 65 years with n ormal retinal examinations. Ophthalmoscopy, color vision testing, visual fi elds, retinal photography, and fluorescein angiography were performed on th e eight patients, Direct DNA sequencing of the exons and nanking intronic r egions of the ABCR gene was completed for all patients. RESULTS: Clinical evaluation confirmed the diagnosis of chloroquine/hydroxy chloroquine retinopathy and excluded Stargardt disease in each patient, Two patients had heterozygous ABCR missense mutations previously associated wi th Stargardt disease. None of the controls had these missense mutations. Th ree other patients had other missense polymorphisms. CONCLUSIONS: Some individuals who have ABCR mutations may be predisposed to develop retinal toxicity when exposed to chloroquine/hydroxychloroquine. W e urge further study of a larger cohort of patients with chloroquine/hydrox ychloroquine retinopathy. (Am J Ophthalmol 2001;131:761-766. (C) 2001 by El sevier Science Inc. All rights reserved,).