Abstract
A number of mutations in the rhodopsin gene have been shown to cause both dominant and recessive retinitis pigmentosa. Here we describe another phenotype associated with a defect in this gene. We discovered a patient with congenital stationary night blindness who carries the missense mutation Ala292Glu. When coupled with 11–cis–retinal in vitro, Ala292Glu rhodopsin is able to activate transducin in a light–dependent manner like wild–type rhodopsin. However, without a chromophore, Ala292Glu opsin anomalously activates transducin. We speculate that the rod dysfunction in this patient is due to an abnormal, continuous activation of transducin by mutant opsin molecules in photoreceptor outer segments.
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References
Schubert, G. & Bornschein, H. Beitrag zur Analyse des menschlichen Elektroretinogramms. Ophthalmologica 123, 396–413 (1952).
Goodman, G. & Bornschein, H. Comparative electroretinographic studies in congenital night blindness and total color blindness. Arch. Ophthalmol. 58, 174–182 (1957).
Hill, D.A., Arbel, K.F. & Berson, E.L. Cone electroretinograms in congenital nyctalopia with myopia. Am. J. Ophthalmol. 78, 127–136 (1974).
Carr, R.E., Ripps, H., Siegel, I.M. & Weale, R.A. Rhodopsin and the electrical activity of the retina in congenital night blindness. Invest. Ophthal. Vis. Sci. 5, 497–507 (1966).
Peachey, N.S. et al. A form of congenital stationary night blindness with apparent defect of rod phototransduction. Invest. Ophthal. Vis. Sci. 31, 237–246 (1990).
Franceschetti, A., Francois, J. & Babel, J. Chorioretinal Heredodegenerations (Charles C. Thomas, Springfield, Illinois, 1963).
Nettleship, E. A history of congenital stationary night-blindness in nine consecutive generations. Trans. Ophthalmol. Soc. UK 27, 269–293 (1907).
Dejean, C. & Gassenc, R. Note sur la genealogie de la famille Nougaret, de Vendemian. Bull. Soc. Ophtal. France 1, 96–99 (1949).
Berson, E.L. in Adler's Physiology of the Eye 9th edn (ed. Hart, W.M.) 641–707 (C.V. Mosby, St. Louis, 1992).
Berson, E.L. Retinitis pigmentosa and allied retinal diseases: electrophysiologic findings. Trans. Am. Acad. Ophthalmol. Otolaryngol. 81, 659–666 (1976).
Oprian, D.D., Molday, R.S., Kaufman, R.S. & Khorana, H.G. Expression of a synthetic rhodopsin gene in monkey kidney cells. Proc. natn. Acad. Sci. U.S.A. 84, 8874–8878 (1987).
Zhukovsky, E.A., Robinson, P.R. & Oprian, D.D. Transducin activation by rhodopsin without a covalent bond to the 11-cis-retinal chromophore. Science 251, 558–560 (1991).
Nakayama, T.A. & Khorana, H.G. Mapping of the amino acids in membrane-embedded helices that interact with the retinal chromophore in bovine rhodopsin. J. biol. Chem. 266, 4269–4275 (1991).
Defoe, D.M. & Bok, D. Rhodopsin chromophore exchanges among opsin molecules in the dark. Invest. Ophthal. Vis. Sci. 24, 1211–1226 (1983).
Van Kuijk, F.J.G.M. et al. Spectrophotometric quantitation of rhodopsin in human retina. Invest. Ophthal. Vis. Sci. 32, 1962–1967 (1991).
Curcio, C.A., Sloan, K.R., Kalina, R.E. & Hendrickson, A.E. Human photoreceptor topography. J. comp. Neurol. 292, 497–523 (1990).
Fulton, A.B. et al. The quantity of rhodopsin in human eyes. Curr. Eye Res. 9, 1211–1216 (1990).
Baylor, D.A., Nunn, B.J. & Schnapf, J.L. The photocurrent, noise and spectral sensitivity of rods of the monkey Macaca fascicularis. J. Physiol. 357, 575–607 (1984).
Sandberg, M.A., Berson, E.L. & Effron, M.H. Rod-cone interaction in the distal human retina. Science 212, 829–831 (1981).
Birch, D.G. & Sandberg, M.A. Dependence of cone b-wave implicit time on rod amplitude in retinitis pigmentosa. Vision Res. 27, 1105–1112 (1987).
Robinson, P.R., Cohen, G.B., Zhukovsky, E.A. & Oprian, D.D. Constitutively active mutants of rhodopsin. Neuron 9, 719–725 (1992).
Inglehearn, C.F. et al. A completed screen for mutations of the rhodopsin gene in a panel of patients with autosomal dominant retinitis pigmentosa. Hum. molec. Genet. 1, 41–45 (1992).
Nathans, J. & Hogness, D.S. Isolation and nucleotide sequence of the gene encoding human rhodopsin. Proc. natn. Acad. Sci. U.S.A. 81, 4851–4855 (1984).
Orita, M., Iwahana, H., Kanazawa, H., Hayashi, K. & Sekiya, T. Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc. natn. Acad. Sci. U.S.A. 86, 2766–2770 (1989).
Dryja, T.P., Hahn, L.B., Cowley, G.S., McGee, T.L. & Berson, E.L. Mutation spectrum of the rhodopsin gene among patients with autosomal dominant retinitis pigmentosa. Proc. natn. Acad. Sci. U.S.A. 88, 9370–9374 (1991).
Yandell, D.W. & Dryja, T.P. in Cold Spring Harbor Symposium Series: Cancer Cells 7 - Molecular Diagnostics of Human Cancer (eds Furth, M. & Greaves, M.) 223–227 (Cold Spring Harbor Press, New York, 1989).
Berson, E.L., Gouras, P. & Gunkel, R.D. Rod responses in retinitis pigmentosa, dominantly inherited. Arch. Ophthalmol. 80, 58–67 (1968).
Reichel, E., Bruce, A.M., Sandberg, M.A. & Berson, E.L. An electroretinographic and molecular genetic study of X-linked cone degeneration. Am. J. Ophthalmol. 108, 540–547 (1989).
Ferretti, L., Karnik, S.S., Khorana, H.G., Nassal, M. & Oprian, D.D. Total synthesis of a gene for bovine rhodopsin. Proc. natn. Acad. Sci. U.S.A. 83, 599–603 (1986).
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Dryja, T., Berson, E., Rao, V. et al. Heterozygous missense mutation in the rhodopsin gene as a cause of congenital stationary night blindness. Nat Genet 4, 280–283 (1993). https://doi.org/10.1038/ng0793-280
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DOI: https://doi.org/10.1038/ng0793-280
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