ABCR UNITES WHAT OPHTHALMOLOGISTS DIVIDE(S)

Over the last years, the molecular causes of monogenic chorioretinal d iseases have been elucidated at an increasing pace. In contrast, only recently have genetic factors been found that contribute to multifacto rial eye disorders such as age-related macular degeneration (AMD). Mut ations in the retina-specific ATP-binding cassette transporter gene (A BCR) cause recessive Stargardt's disease (STGD) and fundus flavimacula tus (FFM), and were also found in 16% of patients with AMD. In additio n, ABCR mutations were identified in families with recessive retinitis pigmentosa (RP), cone dystrophy (COD), and cone-rod dystrophy (CRD). In this review, we summarize these findings and propose a model which provides a framework to explain the observed genotypes and phenotypes. We hypothesize that most ABCR mutations can be classified in differen t classes of severity, and that, depending on the remaining total acti vity of ABCR, the phenotype can range from AMD at the mild end to RP a t the severe end of the spectrum. This model allows us to make several predictions on the type and/or severity of ABCR mutations that are pr esent in patients with AMD, STGD/FFM, GOD, CRD, and RP.