MUTATION SPECTRUM OF THE GENE ENCODING THE BETA-SUBUNIT OF ROD PHOSPHODIESTERASE AMONG PATIENTS WITH AUTOSOMAL RECESSIVE RETINITIS-PIGMENTOSA

Mutations in the gene encoding the beta subunit of rod cGMP phosphodie sterase are known causes of photoreceptor degeneration in two animal m odels 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 pigmentos a for defects in the human homologue of this gene. We identified seven different mutations that cosegregate with the disease. They were foun d among four patients with each patient heterozygously carrying two mu tations. All of these mutations are predicted to affect the putative c atalytic domain, probably leading to a decrease in phosphodiesterase a ctivity and an increase in cGMP levels within rod photoreceptors. Muta tions in the gene encoding the beta subunit of rod phosphodiesterase a re the most common identified cause of autosomal recessive retinitis p igmentosa, accounting for approximate to 4% of cases in North America.