title: Leber congenital amaurosis caused by mutations in GUCY2D.
abstract: Leber congenital amaurosis (LCA) is a clinically and genetically heterogeneous group of diseases that account for the most severe form of early-onset retinal dystrophy. Mutations in retinal guanylate cyclase-1 (GUCY2D) are associated with LCA1, a prevalent form. GUCY2D encodes guanylate cyclase-1 (GC1), a protein expressed in rod and cone photoreceptors that regulates cGMP and Ca(2+) levels within these cells. LCA1 patients present with severely impaired vision, reduced, or ablated electroretinogram and nystagmus. Despite a high degree of visual disturbance, LCA1 patients retain normal photoreceptor laminar architecture, except for foveal cone outer segment abnormalities and, in some patients, foveal cone loss. This article will summarize clinical characterization of patients and proof of concept gene replacement studies in several animal models of GC1 deficiency, both of which have laid the groundwork for clinical application of a gene therapy for treatment of LCA1.
authors.affiliation: Department of Ophthalmology and Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida 32610.
authors.forename: Shannon E
authors.initials: SE
authors.lastname: Boye
mesh_terms: D000818:Animals; D002645:Chickens; D004195:Disease Models, Animal; D006162:Guanylate Cyclase / Q000235:genetics*; D006801:Humans; D057130:Leber Congenital Amaurosis / Q000235:genetics*; D051379:Mice; D009154:Mutation / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*
chemical_list: D011956:Receptors, Cell Surface; C110715:guanylate cyclase 1; D006162:Guanylate Cyclase