Retinitis pigmentosa caused by a homozygous mutation in the Stargardt disease gene ABCR

Retinitis pigmentosa (RP) denotes a group of inherited eye disorders characterized by loss of rod photoreceptor function, leading to a progressive degeneration of the retina. It constitutes a major cause of genetic blindness in adults, with a prevalence of 1 in 3,000-7,000. One of the main features of RP is its extreme heterogeneity, both clinical and genetic. It can be inherited as an X-linked, an autosomal-dominant or an autosomal-recessive trait. Additionally, non-allelic heterogeneity is documented by more than twenty loci and genes, which account for less than 50% of RP cases. Mutations in ten of these loci can cause autosomal-recessive RP (arRP; ). Recently, we mapped a new arRP locus on 1p13-p21 (RP19), which co-localizes with the Stargardt (STGD1) and fundus flavimaculatus (FFM) loci. The causal gene for these allelic disorders has been identified as the retina-specific ATP-binding cassette transporter gene ABCR. Mutations in ABCR have also been identified in age-related macular degeneration (AMD). Although its function as a transporter is not yet well defined, ABCR is located exclusively in the outer segments of rods, and this makes the gene an excellent candidate for the RP19 locus. To test this hypothesis, we performed a mutational analysis of the ABCR gene in the RP19 consanguineous family M-33.