title: Exclusion of five subunits of cGMP phosphodiesterase in Leber's congenital amaurosis.
abstract: Leber's congenital amaurosis (LCA) is the earliest and most severe of all inherited retinal dystrophies. Recently, we mapped an LCA gene to chromosome 17p13.1 (LCA1) and ascribed the disease to mutations of the retinal guanylate cyclase (ret GC) gene in a subset of families of North African ancestry. Owing to the genetic heterogeneity of LCA and considering that LCA1 results from an impaired production of cGMP in the retina (with permanent closure of cGMP-gated cation channels), we hypothesized that the activation of the cGMP phosphodiesterase (PDE) could trigger the disease by lowering the intracellular cGMP level in the retina. The rod and cone cGMP-PDE inhibitory subunits were regarded therefore as candidate genes in LCA. Here, we report the exclusion of five rod and cone cGMP-PDE subunits in LCA families unlinked to chromosome 17p13.
authors.affiliation: Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-393, Département de Génétique, Hôpital des Enfants-Malades, Paris, France.
authors.forename: I
authors.initials: I
authors.lastname: Perrault
authors.forename: S
authors.initials: S
authors.lastname: Châtelin
authors.forename: V
authors.initials: V
authors.lastname: Nancy
authors.forename: J M
authors.initials: JM
authors.lastname: Rozet
authors.forename: S
authors.initials: S
authors.lastname: Gerber
authors.forename: I
authors.initials: I
authors.lastname: Ghazi
authors.forename: E
authors.initials: E
authors.lastname: Souied
authors.forename: J L
authors.initials: JL
authors.lastname: Dufier
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: J
authors.initials: J
authors.lastname: de Gunzburg
authors.forename: J
authors.initials: J
authors.lastname: Kaplan
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000235:genetics*; D001766:Blindness / Q000151:congenital / Q000201:enzymology / Q000235:genetics*; D002877:Chromosomes, Human / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005796:Genes / Q000235:genetics; D008040:Genetic Linkage; D006801:Humans; D007438:Introns / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D017949:Retinal Cone Photoreceptor Cells; D012162:Retinal Degeneration / Q000151:congenital / Q000201:enzymology / Q000235:genetics*; D017948:Retinal Rod Photoreceptor Cells
chemical_list: D015106:3',5'-Cyclic-GMP Phosphodiesterases