Mutations in RPE65 cause Leber's congenital amaurosis

RPE65 is a 65-kD protein specific to the retinal pigment epithelium (RPE; refs 1,2), a monolayer epithelium in close contact with the photoreceptor outer segments. Although the precise role of RPE65 remains unclear, its participation in retinoid metabolism seems certain, and implies a functional relationship of RPE65 with photoreceptor physiology. Given that mutations in photoreceptor-specific genes cause retinal dystrophies, and assuming that a genetic defect in a photoreceptor-related function of RPE, as in the absence of RPE65, might cause an early degeneration of photoreceptors, mutations in the RPE65 gene were sought in patients with Leber's congenital amaurosis (LCA), a disorder characterized by blindness at birth. We sequenced the human RPE65 gene, which contains fourteen coding exons spanning 20 kb. Twelve unrelated LCA patients from whom informed consent had been obtained were screened.