Analysis of the ABCR (ABCA4) gene in 4-aminoquinoline retinopathy: is retinal toxicity by chloroquine and hydroxychloroquine related to Stargardt disease?
OBJECTIVE
To determine if mutations in ABCR (ABCA4) are associated with chloroquine/hydroxychloroquine retinopathy.


METHODS
DNA from eight patients with chloroquine or hydroxychloroquine retinopathy was studied. Controls were 80 individuals over age 65 years with normal retinal examinations. Ophthalmoscopy, color vision testing, visual fields, retinal photography, and fluorescein angiography were performed on the eight patients. Direct DNA sequencing of the exons and flanking intronic regions of the ABCR gene was completed for all patients.


RESULTS
Clinical evaluation confirmed the diagnosis of chloroquine/hydroxychloroquine retinopathy and excluded Stargardt disease in each patient. Two patients had heterozygous ABCR missense mutations previously associated with Stargardt disease. None of the controls had these missense mutations. Three 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. We urge further study of a larger cohort of patients with chloroquine/hydroxychloroquine retinopathy.
Shroyer
N F
NF
Program in Cell and Molecular Biology, Baylor College of Medicine, (Mr Shroyer and Dr Lupski), Houston, Texas, USA
Lewis
R A
RA
Lupski
J R
JR
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000368:Aged; D000634:Aminoquinolines / Q000009:adverse effects*; D002738:Chloroquine / Q000009:adverse effects*; D020022:Genetic Predisposition to Disease; D006801:Humans; D006886:Hydroxychloroquine / Q000009:adverse effects*; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D012016:Reference Values; D012160:Retina / Q000473:pathology; D012164:Retinal Diseases / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology
C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters; D000634:Aminoquinolines; D006886:Hydroxychloroquine; D002738:Chloroquine; C001920:4-aminoquinoline