title: Retinal diseases linked with photoreceptor guanylate cyclase.
abstract: Inherited retinal dystrophies are the main causes of progressive visual impairment often leading to blindness. They represent a clinically and genetically heterogenous group of disorders. Continuously increasing body of evidence links retinal dystrophies to mutations in numerous genes. These genes code for retinal proteins of various function (phototransduction, visual cycle, transcription factors, structural and metabolic functions). Mutations in the gene coding for photoreceptor specific guanylate cyclase type 1, ROS-GC1, were found to be the cause for the type 1 Leber's congenital amaurosis (LCAI) and cone-rod dystrophy type 6 (CORD6). The LCA1-linked mutations are distributed over almost the entire ROS-GCI coding sequence but the CORD6-linked mutations are restricted to three positions, E786, R787 and T788, located within the putative ROS-GC1 dimerization domain. A linkage between the biochemical effect of the mutation and its phenotypic manifestation was provided for only one LCA1 mutation, F514S. This was followed by biochemical analyses of the consequences of the CORD6-causing mutations. Here, an overview on the existing results and a discussion of the possible physiological implications are presented.
authors.affiliation: Department of Cell Biology, SOM and NJMS, University of Medicine and Dentistry of New Jersey, Stratford 08084, USA. dudatm@umdnj.edu
authors.forename: Teresa
authors.initials: T
authors.lastname: Duda
authors.forename: Karl-Wilhelm
authors.initials: KW
authors.lastname: Koch
mesh_terms: D006162:Guanylate Cyclase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009154:Mutation / Q000235:genetics; D029242:Optic Atrophy, Hereditary, Leber / Q000201:enzymology / Q000235:genetics; D020419:Photoreceptor Cells, Vertebrate / Q000201:enzymology*; D012164:Retinal Diseases / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D012374:Rod Cell Outer Segment / Q000201:enzymology
chemical_list: D006162:Guanylate Cyclase