title: ABCR unites what ophthalmologists divide(s)
abstract: Over the last years, the molecular causes of monogenic chorioretinal diseases have been elucidated at an increasing pace. In contrast, only recently have genetic factors been found that contribute to multifactorial eye disorders such as age-related macular degeneration (AMD). Mutations in the retina-specific ATP-binding cassette transporter gene (ABCR) cause recessive Stargardt's disease (STGD) and fundus flavimaculatus (FFM), and were also found in 16% of patients with AMD. In addition, 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 different classes of severity, and that, depending on the remaining total activity of ABCR, the phenotype can range from AMD at the mild end to RP at 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 present in patients with AMD, STGD/FFM, COD, CRD, and RP.
authors.forename: M A
authors.initials: MA
authors.lastname: van Driel
authors.forename: A
authors.initials: A
authors.lastname: Maugeri
authors.forename: B J
authors.initials: BJ
authors.lastname: Klevering
authors.forename: C B
authors.initials: CB
authors.lastname: Hoyng
authors.forename: F P
authors.initials: FP
authors.lastname: Cremers
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D003001:Cloning, Molecular; D005128:Eye Diseases / Q000235:genetics*; D005808:Genes, Recessive / Q000235:genetics; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics; D008957:Models, Genetic; D012174:Retinitis Pigmentosa / Q000235:genetics
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters