Documenta Ophthalmologica

, Volume 107, Issue 1, pp 3–11 | Cite as

RDH5 gene mutations and electroretinogram in fundus albipunctatus with or without macular dystrophy

  • Makoto Nakamura
  • Jason Skalet
  • Yozo Miyake
Article

Abstract

The aim of this study was to analyze the RDH5 gene in patients with fundus albipunctatus with and without macular dystrophy, and correlate the identified mutations with the electrophysiological results. Twenty-one patients from 19 unrelated Japanese families with fundus albipunctatus were examined. Ten unrelated patients had macular dystrophy. In 18 patients, either a homozygous or a compound heterozygous mutation in the RDH5 gene was identified. The bright-flash, mixed rod-cone ERG had a negative configuration with reduced a-wave amplitudes after a short period of dark-adaptation (20 or 30 min). After a prolonged dark-adaptation period (2 or 3 h), the waveform attained normal amplitudes in patients without macular dystrophy but the a-waves were still subnormal in patients with macular dystrophy. The photopic ERG responses were significantly reduced in patients with macular dystrophy, indicating that they also had cone dystrophy. The photopic ERGs were reduced in only some of the patients without macular dystrophy. In patients without macular dystrophy, the scotopic b-wave amplitudes were nonrecordable or significantly reduced after a short dark-adaptation period but then improved to normal levels. However, they did not fully recover in some patients with macular dystrophy. Three patients with macular dystrophy in whom a RDH5 gene mutation could not be detected by our routine method had atypical ERG responses. We conclude that RDH5 gene mutations cause a progressive cone dystrophy or macular dystrophy as well as night blindness. The clinical phenotype including electrophysiological responses varied among patients with the RDH5 gene mutations.

cone dystrophy fundus albipunctatus macular dystrophy molecular genetics RDH5 gene 

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References

  1. 1.
    Krill AE. Hereditary retinal and choroidal diseases. Hagerstown: Harper and Row 1977; 2: 739–824.Google Scholar
  2. 2.
    Marmor MF. Long-term follow-up of the physiologic abnormalities and fundus changes in fundus albipunctatus. Ophthalmology 1990; 97: 380–4.Google Scholar
  3. 3.
    Heckenlively J. Congenital stationary night blindness. Genetic diseases of the eye. New York: Oxford University Press 1998; 389–96.Google Scholar
  4. 4.
    Yamamoto H, Simon A, Eriksson U, Harris E, Berson EL, Dryja TP. Mutations in the gene encoding 11-cis retinol dehydrogenase cause delayed dark adaptation and fundus albipunctatus. Nat Genet 1999; 22: 188–91.Google Scholar
  5. 5.
    Nakamura M, Hotta Y, Tanikawa A, Terasaki H, Miyake Y. A high association with cone dystrophy in fundus albipunctatus caused by mutations of the RDH5 gene. Invest Ophthalmol Vis Sci 2000; 41: 3925–32.Google Scholar
  6. 6.
    Gonzalez-Fernandez F, Kurz D, Bao Y, Newman S, Conway BP, Young JE, Han DP, Khani SC. 11-cis Retinol dehydrogenase mutations as a major cause of the congenital nightblindness disorder known as fundus albipunctatus. Mol Vision 1999; 5: 41.Google Scholar
  7. 7.
    Wada Y, Abe T, Fuse N, Tamai M. A frequent 1085delC/insGAAG mutation in the RDH5 gene in Japanese patients with fundus albipunctatus. Invest Ophthalmol Vis Sci 2000; 41: 1894–7.Google Scholar
  8. 8.
    Hirose E, Inoue Y, Morimura H, Okamoto N, Fukuda M, Yamamoto S, Fujikado T, Tano Y. Mutations in the 11-cis retinol dehydrogenase gene in Japanese patients with fundus albipunctatus. Invest Ophthalmol Vis Sci 2000; 41: 3933–5.Google Scholar
  9. 9.
    Kuroiwa S, Kikuchi T, Yoshimura N. A novel compound heterozygous mutation in the RDH5 gene in a patient with fundus albipunctatus. Am J Ophthalmol 2000; 130: 672–5.Google Scholar
  10. 10.
    Yamamoto H, Fishman GA, Berson EL, Dryja TP. Three novel mutations in the RDH5 gene encoding 11-cis retinol dehydrogenase in patients with fundus albipunctatus. Invest Ophthalmol Vis Sci 2000; 41: s615.Google Scholar
  11. 11.
    Nakamura M, Hotta Y, Miyake Y. Japanese patients with fundus albipunctatus caused by RDH5 gene mutations. In Anderson RE, LaVail MM, Hollyfield JG, eds. New insights into retinal degenerative diseases. NewYork: Kluwer Academic/ Plenum. 2001: 29–35.Google Scholar
  12. 12.
    Wada Y, Abe T, Sato H, Tamai M. A novel Gly35Ser mutation in the RDH5 gene in a Japanese family with fundus albipunctatus associated with cone dystrophy. Arch Ophthalmol 2001; 119: 1059–63.Google Scholar
  13. 13.
    Driessen CA, Janssen BP, Winkens HJ, Kuhlmann LD, Van Vugt AH, Pinckers AJ, Deutman AF, Janssen JJ. Null mutation in the human 11-cis retinol dehydrogenase gene associated with fundus albipunctatus. Ophthalmology 2001; 108: 1479–84.Google Scholar
  14. 14.
    Nakamura M, Miyake Y. Macular dystrophy in a 9-year-old boy with fundus albipunctatus. Am J Ophthalmol 2002; 133: 278–80.Google Scholar
  15. 15.
    Miyazaki K, Murakami A, Imamura S, Yoshii M, Ishida M, Washio N, Okisaka S. A case of fundus albipunctatus with a retinol dehydrogenase 5 gene mutation in a child. Jpn J Ophthalmol 2002; 46: 121–2.Google Scholar
  16. 16.
    Miyake Y, Shiroyama N, Sugita S, Horiguchi M, Yagasaki K. Fundus albipunctatus associated with cone dystrophy. Br J Ophthalmol 1992; 76: 375–9.Google Scholar
  17. 17.
    Morimura H, Berson EL, Dryja TP. Recessive mutations in the RLBP1 gene encoding cellular retinaldehyde-binding protein in a form of retinitis punctata albescens. Invest Ophthalmol Vis Sci 1999; 40: 1000–4.Google Scholar
  18. 18.
    Katsanis N, Shroyer NF, Lewis RA, Cavender JC, Al-Rajhi AA, Jabak M, Lupski JR. Fundus albipunctatus and retinitis punctata albescens in a pedigree with an R150Q mutation in RLBP1. Clin Genet 2001; 59: 424–9.Google Scholar

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Makoto Nakamura
    • 1
  • Jason Skalet
    • 1
  • Yozo Miyake
    • 1
  1. 1.Department of OphthalmologyNagoya University School of MedicineShowa-ku, NagoyaJapan

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