Leber congenital amaurosis and retinitis pigmentosa with coats-like exudative vasculopathy are associated with mutations in the crumbs homologue 1 (CRB1) gene

Mutations in the crumbs homologue 1 (CRB1) gene cause a specific form of re tinitis pigmentosa (RP) that is designated "RP12" and is characterized by a preserved para-arteriolar retinal pigment epithelium (PPRPE) and by severe loss of vision at age <20 years. Because of the early onset of disease in patients who have RP with PPRPE, we considered CRB1 to be a good candidate gene for Leber congenital amaurosis (LCA). Mutations were detected in 7 (13 %) of 52 patients with LCA from the Netherlands, Germany, and the United St ates. In addition, CRB1 mutations were detected in five of nine patients wh o had RP with Coats-like exudative vasculopathy, a relatively rare complica tion of RP that may progress to partial or total retinal detachment. Given that four of five patients had developed the complication in one eye and th at not all siblings with RP have the complication, CRB1 mutations should be considered an important risk factor for the Coats-like reaction, although its development may require additional genetic or environmental factors. Al though no clear-cut genotype-phenotype correlation could be established, pa tients with LCA, which is the most severe retinal dystrophy, carry null all eles more frequently than do patients with RP. Our findings suggest that CR B1 mutations are a frequent cause of LCA and are strongly associated with t he development of Coats-like exudative vasculopathy in patients with RP.