Abstract
RPE65 encodes a retinal pigment epithelium (RPE)-specific protein thought to be involved in the 11 -cis retinoid metabolism, a key process in vision.To evaluate the visual implications of defects in this gene, we screened patients with various types of inherited retinal dystrophies. We found two nonsense mutations, 1121delA and R234X, in two sibs with Leber’s congenital amaurosis. The presence of either one of the two mutations on each allele indicates that they were compound heterozygotes. In a subsequent screening, two missense mutations, L22P and H68Y, were found in a patient with autosomal recessive retinitis pigmentosa.This individual was also a compound heterozygote. These results suggest that the level of impairment of the RPE65 protein, presumably abnormal activity in the case of amino acid substitutions and absence of protein in the case of null mutations, controls the rate at which the photoreceptors degenerate, and hence the severity of the phenotype.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
K.M. Zinn and M.F. Marmor, 1978, The retinal pigment epithelium, Hrvard University Press, Cambridge.
R.W. Young and D. Bok, 1969, Participation of the retinal pigment epithelium in the rod outer segment renewal process, J. Cell Biol. 42:392–403.
D. Bok and M.O. Hall, 1971, The role of the pigment epithelium in the etiology of inherited retinal dystrophy in the rat, J. Cell Biol. 49:664–682.
G. Wald, 1968, The molecular basis of visual excitation, Nature 219:800–807.
C.P. Hamel, E. Tsilou, E. Harris, B.A. Pfeffer, J.J. Hooks, B. Detrick, and T.M. Redmond, 1993, A developmentally regulated microsomal protein specific for the pigment epithelium of the vertebrate retina, J. Neurosci. Res. 34:414–425.
R.K. Crouch, P. Goletz, S. Yu, and T.M. Redmond, 1997, A possible role for RPE65 in retinoid processing, Invest. Ophthalmol. Vis. Sci. 38:S304.
S.-M. Gu, D.A. Thompson, C.R. Srisailapathy Srikumari, B. Lorenz, U. Finckh, A. Nicoletti, K.R. Murthy, M. Rathmann, G. Kumaramanickavel, M.J. Denton, and A. Gal, 1997, Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy, Nature. Genet. 17:194–197.
F. Marlhens, C. Bareil, J.M. Griffoin, E. Zrenner, P. Amalric, C. Eliaou, S.Y. Liu, E. Harris, T.M. Redmond, B. Arnaud, M. Claustres, and C.P. Hamel, 1997, Mutations in RPE65 cause Leber’s congenital amaurosis, Nature Genet. 17:5–7.
H. Morimura, G.A. Fishman, S.A. Grover, A.B. Fulton, E.L. Berson, and T.P. Dryja, 1998, Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or Leber’s congenital amaurosis, Proc. Natl. Acad. Sci. USA 95:3088–3093.
F. Marlhens, J.-M. Griffoin, C. Bareil, B. Arnaud, M. Claustres, and C.P. Hamel, 1998, Autosomal recessive retinal dystrophy associated with two novel mutations in the RPE65 gene, Eur. J. Hum. Genet. in press.
A. Nicoletti, D.J. Wong, K. Kawase, K.H. Gibson, T. L. Yang-Feng, J.E. Richards, and D.A. Thompson, 1995, Molecular characterization of the human gene encoding an abundant 61 kDa protein specific to the retinal pigment epithelium, Hum. Molec. Genet. 4:641–649.
C.P. Hamel, E. Tsilou, B.A. Pfeffer, J.J. Hooks, B. Detrick, and T.M. Redmond, 1993, Molecular cloning and expression of RPE65, a novel retinal pigment epithelium-specific microsomal protein that is posttranscriptionally regulated in vitro, J. Biol. Chem. 268:15751–15757.
G. Manès, R. Leducq, J. Kucharczak, A. Pages, C.F. Schmitt-Bernard, and C.P. Hamel, 1998, Rat messenger RNA for the retinal pigment epithelium-specific protein RPE65 gradually accumulates in two weeks from late embryonic days, FEBS Lett. 423:133–137.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1999 Kluwer Academic / Plenum Publishers
About this chapter
Cite this chapter
Hamel, C.P., Marlhens, F., Griffoin, JM., Bareil, C., Claustres, M., Arnaud, B. (1999). Different Mutations in RPE65 Are Associated with Variability in the Severity of Retinal Dystrophy. In: Hollyfield, J.G., Anderson, R.E., LaVail, M.M. (eds) Retinal Degenerative Diseases and Experimental Therapy. Springer, Boston, MA. https://doi.org/10.1007/978-0-585-33172-0_3
Download citation
DOI: https://doi.org/10.1007/978-0-585-33172-0_3
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-306-46193-4
Online ISBN: 978-0-585-33172-0
eBook Packages: Springer Book Archive