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Autosomal recessive retinitis pigmentosa caused by mutations in the α subunit of rod cGMP phosphodiesterase

Nature Genetics volume 11, pages 468–471 (1995)Cite this article

Abstract

Retinitis pigmentosa (RP) constitutes a group of genetically heterogeneous progressive photore-ceptor degenerations leading to blindness and affecting 50,000–100,000 people in the U.S. alone. Over 20 different RP loci have been mapped1, of which six have been identified. Three of these encode members of the rod photoreceptor visual transduction cascade2: rhodopsin3, the rod cGMP-gated cation channel α subunit4, and the β subunit of cGMP-phosphodiesterase (PDEB)5. As null mutations in PDEB cause some cases of RP and since both α and β subunits are required for full phosphodiesterase activity, we examined the gene encoding the α 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.

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Authors and Affiliations

  1. The Berman-Gund Laboratory study of Retinal Degenerations and the Taylor smith Laboratory, Haward Medical school Massachusetts Eye and Ear Infirmary, 243 Charles street, Boston, Massachusetts, 02114, USA

    Sherleen H. Huang, Eliot L. Berson & Thaddeus P. Dryja

  2. Department of Biochemistry and Molecuar Biology, University of South Alabama College of Medicine, 307 University Boulevard, Mobile, Alabama, 36688, USA

    Steven J. Pittler, Xizhong Huang & Luanne Oliveira

  3. Department of Opthalmology, University of South Alabama College of Medicine, 307 University Boulevard, Mobile, Alabama, 36688, USA

    Steven J. Pittler

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Huang, S., Pittler, S., Huang, X. et al. Autosomal recessive retinitis pigmentosa caused by mutations in the α subunit of rod cGMP phosphodiesterase. Nat Genet 11, 468–471 (1995). https://doi.org/10.1038/ng1295-468

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