title: Autosomal recessive retinitis pigmentosa caused by mutations in the alpha subunit of rod cGMP phosphodiesterase.
abstract: Retinitis pigmentosa (RP) constitutes a group of genetically heterogeneous progressive photoreceptor degenerations leading to blindness and affecting 50,000-100,000 people in the U.S. alone. Over 20 different RP loci have been mapped, of which six have been identified. Three of these encode members of the rod photoreceptor visual transduction cascade: rhodopsin, the rod cGMP-gated cation channel alpha subunit, and the beta subunit of cGMP-phosphodiesterase (PDEB). As null mutations in PDEB cause some cases of RP and since both alpha and beta subunits are required for full phosphodiesterase activity, we examined the gene encoding the alpha subunit of cGMP phosphodiesterase (PDEA) in 340 unrelated patients with RP. We found three point mutations in PDEA in affected members of two pedigrees with recessive RP. Each mutation alters an essential functional domain of the encoded protein and likely disrupts its catalytic function. PDEA is the seventh RP gene identified, highlighting the extensive genetic heterogeneity of the disorder and encouraging further investigation into the role of other members of the phototransduction cascade in RP.
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002895:Chromosomes, Human, Pair 5; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D018740:Genetic Heterogeneity; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D017948:Retinal Rod Photoreceptor Cells / Q000201:enzymology*; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000503:physiopathology
chemical_list: D005136:Eye Proteins; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; C410522:PDE6A protein, human; C096885:PDE6C protein, human