Advertisement

Phenotypes of Carboxyl-Terminal Rhodopsin Mutations in Autosomal Dominant Retinitis Pigmentosa

  • Eckart Apfelstedt-Sylla
  • Susanna Bunge
  • Dezsö David
  • Klaus Rüther
  • Andreas Gal
  • Eberhart Zrenner

Abstract

We compared the ocular findings in 13 patients from 4 families with autosomal dominant retinitis pigmentosa and 4 different mutations in the carboxyl-terminal sequence of rhodopsin. Phenotypic similarities were found among patients with point mutations predicting the amino acid changes valine-345-methionine, proline-347-serine or proline-347-leucine in the rhodopin molecule. These patients had no measurable rod function and an early impairment of cone function, which was most profound in the proline-347-serine genotype. One patient with a valine-345-methionine mutation showed a regional predilection of fundus abnormalities and cone sensitivity loss. A different phenotype with relatively mild disease expression could be observed in a family with a deletion of 8 base pairs (codons 341–343). One 34 year-old member showed regionally varying rod sensitivity loss, which was less severe in the peripheral visual field, and well maintained cone function, as measured by electroretinography and psychophysical tests.

Keywords

Retinitis Pigmentosa Horizontal Meridian Ocular Finding Rhodopsin Gene Rhodopsin Molecule 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    T.P. Dryja, T.L. McGee, E. Reichel, L.B. Hahn, G.S. Cowley, D.W. Yandell, M.A. Sandberg, and E.L. Berson, A point mutation of the rhodopsin gene in one form of retinitis pigmentosa, Nature 343, 346–366 (1990).CrossRefGoogle Scholar
  2. 2.
    C.F. Ingleheam, T.J. Keen, R. Bashir, M. Jay, F. Fitzke, A.C. Bird, A. Crombie, and S. Bhattacharya, A completed screen for mutations of the rhodopsin gene in a panel of patients with autosomal dominant retinitis pigmentosa, Hum. Mol. Genet. 1, 41–45 (1992).CrossRefGoogle Scholar
  3. 3.
    T.P. Dryja, L.B. Hahn, G.S. Cowley, T.L. McGee, and E.L. Berson, Mutation spectrum of the rhodopsin gene among patients with autosomal dominant retinitis pigmentosa, Proc. Natl. Acad. Sci. USA 88, 9370–9374 (1991).PubMedCrossRefGoogle Scholar
  4. 4.
    S. Bunge, H. Wedemann, D. David, D.J. Terwillinger, C. Aulehla-Scholz, C. Sammans, M. Horn, J. Ott, E. Schwinger, E.M. Bleeker-Wagemakers, A.Schinzel, and A. Gal, Molecular analysis and genetic mapping of the rhodopsin gene in families with autosomal dominant retinitis pigmentosa, submitted for publication.Google Scholar
  5. 5.
    V.C. Sheffield, G.A. Fishman, J.S. Beck, A.E. Limura, and E.M. Stone, Identification of novel rhodopsin mutations associated with retinitis pigmentosa using GC-clamped denaturing gel electrophoresis, Am. J. Hum. Genet. 49, 699–706 (1991).PubMedGoogle Scholar
  6. 6.
    C.-H. Sung, C.M. Davenport, J.C. Hennessey, I.H. Maumenee, S.G. Jacobson, J.R. Heckenlively, R. Nowakowski, G. Fishman, P. Gouras, and J. Nathans, Rhodopsin mutations in autosomal dominant retinitis pigmentosa, Proc. Natl. Acad. Sci. USA 88, 6481–6485 (1991).PubMedCrossRefGoogle Scholar
  7. 7.
    P.A. Hargrave, and P.J. O’Brien, Speculations on the molecular basis of retinal degeneration in retinitis pigmentosa, in: “Retinal Degenerations”, R.E. Anderson, J.G. Hollyfield, and M.M. LaVail, Eds., Boca Raton, Florida, CRC Press Inc., 517–528 (1991).Google Scholar
  8. 8.
    P.A. Hargrave, and J.H. McDowell, Rhodopsin and phototransduction: a model system for G protein-linked receptors, FASEB 6, 2323–2331 (1992).Google Scholar
  9. 9.
    E.L. Berson, B. Rosner, M.A. Sandberg, C. Weigel-DiFranco, and T.P. Dryja, Ocular findings in patients with autosomal dominant retinitis pigmentosa and rhodopsin, proline-347-leucine, Am. J. Ophthalmol. 111, 614–623 (1991).PubMedGoogle Scholar
  10. 10.
    E.L. Berson, M.A. Sandberg, and T.P. Dryja, Autosomal dominant retinitis pigmentosa with rhodopsin, valine-345-methionine, Tr. Am. Ophth. Soc. 89, 117–130 (1991).PubMedGoogle Scholar
  11. 11.
    E. Apfelstedt-Sylla, M. Kunisch, M. Horn, K. Ruether, A. Gal, and E. Zrenner, Diffuse loss of rod function in autosomal dominant retinitis pigmentosa with pro-347-leu mutation of rhodopsin. German.J. Ophthalmol. 1: 319–327 (1992).Google Scholar
  12. 12.
    G. Niemeyer, P. Trueb, A. Schinzel, and A. Gal, Clinical and ERG data in a family with autosomal dominant RP and pro-347-arg mutation in the rhodopsin gene, Doc. Ophthalmol. 79, 303–311 (1992).PubMedCrossRefGoogle Scholar
  13. 13.
    S.G. Jacobson, C.M. Kemp, C.-H. Sung, and J. Nathans, Retinal function and rhodopsin levels in autosomal dominant retinitis pigmentosa with rhodopsin mutations. Am. J. Ophthalmol. 112, 256–271 (1991).PubMedGoogle Scholar
  14. 14.
    M. Horn, P. Humphries, M. Kunisch, C. Marchese, E. Apfelstedt-Sylla, L. Fugi, E. Zrenner, P. Kenna, A. Gal, and J. Farrar, Deletions in exon 5 of the human rhodopsin gene causing shift in the reading frame and autosomal dominant retinitis pigmentosa. Hum. Genet. 90, 255–257 (1992).PubMedCrossRefGoogle Scholar
  15. 15.
    G.A. Fishman, K.R. Alexander, and R.J. Anderson, Autosomal dominant retinitis pigmentosa: a method of classification, Arch. Ophthalmol. 103, 366–374 (1985).PubMedCrossRefGoogle Scholar
  16. 16.
    R.W. Massof, and D. Finkelstein, Rod sensitivity relative to cone sensitivity in retinitis pigmentosa, Invest. Ophthalmol. Vis. Sci. 18, 263–272 (1979).PubMedGoogle Scholar
  17. 17.
    W.W. Dawson, G.L. Trick, and C. Litzkow, Improved electrode for electroretinography, Invest. Ophthalmol. Vis. Sci. 18, 988–991 (1979).Google Scholar
  18. 18.
    M.F. Marmor, G.B. Arden, S.E.G. Nilsson, and E. Zrenner, Standard for clinical electroretinography, Arch. Ophthalmol. 107, 816–819 (1989).CrossRefGoogle Scholar
  19. 19.
    R.W. Massof, and D. Finkelstein, Two forms of autosomal dominant primary retinitis pigmentosa, Doc. Opthalmol. 51, 289–346 (1981).CrossRefGoogle Scholar
  20. 20.
    E.L. Berson, B. Rosner, M.A. Sandberg, and T.P. Dryja, Ocular findings in patients with autosomal dominant retinitis pigmentosa and a rhodopsin gene defect (pro-23-his), Arch. Ophthalmol. 109, 92–101 (1991).PubMedCrossRefGoogle Scholar
  21. 21.
    J.R. Heckenlively, J.A. Rodriguez, and P. Daiger, Autosomal dominant sectoral retinitis pigmentosa; two families with transversion mutation in codon 23 of rhodopsin, Arch. Ophthalmol. 109, 84–91 (1991).PubMedCrossRefGoogle Scholar
  22. 22.
    C.M. Kemp, S.G. Jacobson, A.J. Roman, C.-H. Sung, and J. Nathans, Abnormal rod dark adaptation in autosomal dominant retinitis pigmentosa with proline-23-histidine rhodopsin mutation, Am. J. Ophthalmol. 113, 165–174 (1992).PubMedGoogle Scholar
  23. 23.
    E.M. Stone, A.E. Kimura, B.E. Nichols, P. Khadivi, G.A. Sheffield, and V.C. Sheffield, Regional distribution of retinal degeneration in patients with the proline to histidine mutation in codon 23 of the rhodopsin gene, Ophthalmology 98, 1806–1813 (1991).PubMedGoogle Scholar
  24. 24.
    J.E. Richards, K. Chen-Yu, M. Boehnke, and P.A. Sieving, Rhodopsin thr58arg mutation in a family with autosomal dominant retinitis pigmentosa, Ophthalmology 98, 1797–1805 (1991).PubMedGoogle Scholar
  25. 25.
    G.A. Fishman, E.M. Stone, V.C. Sheffield, L.D. Gilbert, and A.E. Kimura, Ocular findings associated with rhodopsin gene codon 17 and codon 182 transition mutations in dominant retinitis pigmentosa, Arch. Ophtalmol. 110, 54–62 (1992).CrossRefGoogle Scholar
  26. 26.
    G.A. Fishman, E.M. Stone, L.D. Gilbert, and V.C. Sheffield, Ocular findings associated with a rhodopsin gene codon 106 mutation, Arch. Ophthalmol. 110, 646–653 (1992).PubMedCrossRefGoogle Scholar
  27. 27.
    C.-H. Sung, B.G. Schneider, N. Agarwal, D.S. Papermaster, and J. Nathans, Functional heterogeneity of mutant rhodopsins responsible for autosomal dominant retinitis pigmentosa, Proc. Natl. Acad. Sci. USA 88, 8840–8844 (1991).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Eckart Apfelstedt-Sylla
    • 1
  • Susanna Bunge
    • 2
  • Dezsö David
    • 2
  • Klaus Rüther
    • 1
  • Andreas Gal
    • 2
  • Eberhart Zrenner
    • 1
  1. 1.Department of Pathophysiology of Vision and Neuro-OphthalmologyUniversity Eye HospitalTuebingenGermany
  2. 2.Department of Human GeneticsMedical UniversityLuebeckGermany

Personalised recommendations