Mutation Spectrum of the Gene Encoding the β Subunit of Rod Phosphodiesterase Among Patients with Autosomal Recessive Retinitis Pigmentosa

• Published in: Proceedings of the National Academy of Sciences - PNAS 1995-04, Vol.92 (8), p.3249-3253
• Main Authors: McLaughlin, Margaret E., Ehrhart, Traci L., Berson, Eliot L., Dryja, Thaddeus P.
• Format: Article
• Language: English
• Subjects: 3',5'-Cyclic-GMP Phosphodiesterases - genetics; 3',5'-cyclic-nucleotide phosphodiesterase; Amino Acid Sequence; Amino acids; Base Sequence; Cohort Studies; Disease; DNA; Exons; Exons - genetics; Female; Genes; Genes, Recessive - genetics; Genetic mutation; Genetic screening; Humans; Introns; Male; man; Medical screening; Molecular Sequence Data; Mutation; mutation frequency; Pedigree; Photoreceptors; Polymerase Chain Reaction; Polymorphism, Genetic; population genetics; Retina; Retinal degeneration; Retinal Rod Photoreceptor Cells - enzymology; Retinitis pigmentosa; Retinitis Pigmentosa - genetics; rods; Sequence Analysis, DNA
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.8.3249

Mutations in the gene encoding the β subunit of rod cGMP phosphodiesterase are known causes of photoreceptor degeneration in two animal models of retinitis pigmentosa, the rd (retinal degeneration) mouse and the Irish setter dog with rod/cone dysplasia. Here we report a screen of 92 unrelated patients with autosomal recessive retinitis pigmentosa for defects in the human homologue of this gene. We identified seven different mutations that cosegregate with the disease. They were found among four patients with each patient heterozygously carrying two mutations. All of these mutations are predicted to affect the putative catalytic domain, probably leading to a decrease in phosphodiesterase activity and an increase in cGMP levels within rod photoreceptors. Mutations in the gene encoding the β subunit of rod phosphodiesterase are the most common identified cause of autosomal recessive retinitis pigmentosa, accounting for ≈4% of cases in North America.