Abstract
Peripherin/RDS, a photoreceptor-specific glycoprotein, located in the peripheral portion of the disc membranes of photoreceptor outer segments of both rods and cones (1–4). Although the precise function of this protein is still uncertain, it has been postulated that peripherm/RDS plays an important role in maintaining the unique structure of the disc membrane. Since a mutation in the peripherin/RDS gene was found to be responsible for retinal degeneration in the rds (retinal degeneration slow) mouse strain (3,4), mutations in the human peripherin/RDS gene have been identified in patients with autosomal dominant retinitis pigmentosa (adRP) (5–10). In addition to typical retinitis pigmentosa, increased numbers of mutations have been identified in the peripherin/RDS gene in families with several kinds of macular dystrophy (8,11), retinitis punctata albescens (12), butterfly-shaped pigment dystrophy of the fovea (13), and fundus flavimaculatus (14). Because peripherm/RDS commonly expressed in both rods and cones, mutations in the peripherin/RDS gene produce either rod- or cone-predominant retinal degeneration, depending on the kinds and locations of mutations. These genotype-phenotype correlations provide important clues not only for better understanding the mechanisms of photoreceptor degeneration produced by mutations in the peripherin/RDS gene, but also for proper genetic counseling based on the accumulated findings regarding clinical courses of patients with known mutations.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Arikawa, K, Molday, R.S., and Wlliams, D.S., 1992, Localization of peripherin/RDS in the disk membranes of cone and rod photoreceptors: relationship to disk membrane morphogenesis and retinal degeneration, J Cell Biol. 116: 659–667.
Connel, G., and Molday, R.S., 1990, Molecular cloning, primary structure and orientation of the vertebrate photoreceptor cell protein peripherin in the rod disc membrane. Biochemistry 29:4691–4698.
Connel, G., Bascom, R., Molday, L., Reid, D., Mclnnes, R.R., and Molday, R.S., 1991, Photoreceptor cell peripherin is the normal product of the gene responsible for the retinal degeneration in the RDS mouse. Proc. Natl. Acad. Sci. U.S.A. 88:723–726.
Travis, G.H., Brennan, M.B., Danielson, P.E., Kozak, C.A., and Sutcliffe, J.G., 1989, Nature 338:70–73.
Kajiwara, K., Hahn, L. B., Mukai, S., Travis, G. H., Berson, E. L., and Dryja, T.P., 1991, Mutations in the human retinal degeneration slow gene in autosomal dominant retinitis pigmentosa. Nature 354: 480–483.
Farrar, G. J., Kenna, P., Jordan, S. A., Kumar-Singh, R., Humphries, M. M., Sharp, E. M., Sheils, D., and Humphries, P., 1991, A three-base pair deletion in periphcrin/RDS gene in one form of retinitis pigmentosa. Nature 354: 478–480.
Farrar, G. J., Kenna, P., Jordan, S. A., Kumar-Singh, R., Humpgries, M. M., Sharp, E. M., Sheils, D., and Humphries, P., 1992, Autosomal dominant retinitis pigmentosa: A novel mutation at the peripherin/RDS locus in the original 6p-linked pedigree. Genomics 14: 805–807.
Wells, J., Wroblewski, J., Keen, J., Inglehearn, C., Jubb, C., Eckestein, A., Jay, M., Arden, G., Bhattacharya, S., Fitzke, F., and Bird, A., 1993, Mutations in the human retinal degeneration slow (RDS) gene can cause either retinitis pigmentosa or macular dystrophy. Nature Genet. 3: 213–218.
Kajiwara, K., Berson, E. L., and Dryja, T. P., Screen for mutations in the entire coding sequence of the human RDS/peripherin gene in patients with hereditary retinal degeneration. Invest. Ophthalmol. Vis. Sci. 34: 1149.
Saga, M., Mashima, Y., Akeo, K., Oguchi, Y, Kudoh, J., and Shimizu, N., 1993, A novel Cys-214-Ser mutation in the peripherin/RDS gene in a Japanese family with autosomal dominant retinitis pigmentosa. Human Genet. 92: 519–521.
Wroblewski, J. J., Wells III, J. A., Eckstein, A., Fitzke, F., Jubb, C., Keen, T. J., Inglehearn, C., Bhattacharya, S., Arden, G. B., Jay, M., and Bird, A., 1994, Macular dystrophy associated with mutations at codon 172 in the human retinal degeneration slow gene. Ophthalmology 101: 12–22.
Kajiwara, K., Sandberg, M. A., Berson, E. L., and Dryja, T. P., 1993, A null mutation in the human peripherin/ßAS gene in a family with autosomal dominant retinitis punctata albescens. Nature Genet. 3: 208–212.
Nichols, B. E., Shefield, V. C., Vandenburgh, K., Drack, A. V., Kimura, A., E., and Stone, E. M., 1993, Butterfly-shaped pigment dystrophy of the fovea caused by a point mutation in codon 167 of the RDS gene. Nature Genet. 3: 202–207.
Weieber, R. G., Carr, R. E., Murphy, W. H., Shefield, V. C., and Stone, E. M., 1993, Phenotypic variation including retinitis pigmentosa, pattern dystrophy, and fundus flavimaculatus in a single family with a deletion of codon 153 or 154 of the peripherin/RDS gene. Arch. Ophthatmol. 111: 1531–1542.
Kikawa, E., Nakazawa, M., Chida, Y, Shiono, T., and Tamai, M., 1994, A novel mutation (Asn244Lys) in the peripherin/RDS gene causing autosomal dominant retinitis pigmentosa associated with bull’s-eye maculopathy detected by nonradioisotopic SSCP. Genomics, 20:137–139.
Nakazawa, M., Kikawa, E., Chida, Y, and Tamai, M., 1994, Asn244His mutation of the peripherin/RDS gene causing autosomal dominant cone-rod degeneration. Human Mol. Genet. 3: 1195–1196.
Nakazawa, M., Kikawa, E., Chida, Y, Shiono, T., and Tamai, M., 1993, Nonradioactive single strand conformation polymorphism (PCR-SSCP): A simplified method applied to a molecular genetic screening of retinitis pigmentosa. In Hollyfield, J. G., LaVail, M. M., Anderson, R. E. (eds.): Retinal Degeneration: Clinical and Laboratory Applications, New York, Plenum Publishing Corp., pp. 181–188.
Gamier, J., Osguthorpe, D. J., and Robson, B., 1978, Analysis of the accuracy and implications of simple methods for predicting the second structure of globular proteins. J. Mol. Biol. 120:97–120.
Nakazawa, M., Kikawa, E., Kamio, K., Chida, Y., Shiono, T., and Tamai, M., 1994, Ocular findings in patients with autosomal dominant retinitis pigmentosa and transversion mutation in codon 244 (Asn244Lys) of the peripherin/RDS gene, Arch. Ophthalmol. 112:1567–1572.
Szlyk, J. P., Fishman, G. A., Alexander, K. R., Peachery, N. S., and Derlacki, D. J., 1993, Clinical subtypes of cone-rod dystrophy. Arch. Ophthalmol. 111: 781–788.
Hayasaka, S., 1983, Lysosomal enzymes in ocular tissues and diseases. Surv. Ophthalmol. 27: 245–258.
Hayasaka, S., Shiono, T., Hara, S., and Mizuno, K., 1981, Regional distribution of lysosomal enzymes in the retina and choroid of human eyes. Albrecht von Graefes Arch. Klin. Ophthalmol. 216: 269–273.
Deutman, A. F., 1977, Rod cone dystrophy: Primary hereditary pigmentary retinopathy, retinitis pigmentosa. In Krill, A. E. (ed.) Krill’s Hereditary Retinal and Choroidal Disease vol. II, Clinical Characteristics, Hagerstown, Harper and Row, pp. 479–576.
Pagon, R. A.: Retinitis pigmentosa. Surv. Ophthalmol. 33: 137–177.
Heckenlively, J. R., 1988, Autosomal dominant retinitis pigmentosa. In Heckenlively, J. R. (ed.) Retinitis Pigmentosa, Philadelphia, Lippincott, pp. 125–149.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1995 Springer Science+Business Media New York
About this chapter
Cite this chapter
Nakazawa, M. et al. (1995). Genotype-Phenotype Correlation in Autosomal Dominant Retinal Degeneration With Mutations in the Peripherin/RDS Gene. In: Anderson, R.E., LaVail, M.M., Hollyfield, J.G. (eds) Degenerative Diseases of the Retina. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1897-6_32
Download citation
DOI: https://doi.org/10.1007/978-1-4615-1897-6_32
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-5774-2
Online ISBN: 978-1-4615-1897-6
eBook Packages: Springer Book Archive