A single EFEMP1 mutation associated with both Malattia Leventinese and Doyne honeycomb retinal dystrophy (original) (raw)

Nature Genetics volume 22, pages 199–202 (1999)Cite this article

Abstract

Malattia Leventinese (ML) and Doyne honeycomb retinal dystrophy (DHRD) refer to two autosomal dominant diseases characterized by yellow-white deposits known as drusen that accumulate beneath the retinal pigment epithelium1,2,3,4 (RPE). Both loci were mapped to chromosome 2p16-21 (Refs 5,6) and this genetic interval has been subsequently narrowed6,7. The importance of these diseases is due in large part to their close phenotypic similarity to age-related macular degeneration (AMD), a disorder with a strong genetic component8,10 that accounts for approximately 50% of registered blindness in the Western world11,12,13,14. Just as in ML and DHRD, the early hallmark of AMD is the presence of drusen15,16. Here we use a combination of positional and candidate gene methods to identify a single non-conservative mutation (Arg345Trp) in the gene EFEMP1 (for EGF-containing fibrillin-like extracellular matrix protein 1) in all families studied. This change was not present in 477 control individuals or in 494 patients with age-related macular degeneration. Identification of this mutation may aid in the development of an animal model for drusen, as well as in the identification of other genes involved in human macular degeneration.

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Acknowledgements

We thank S. Sneed, T. Polk, J.D.M. Gass, J. Slakter, L. Yannuzzi, D. Keenum, A. Franceschetti, S. Forni, C. Anastasi-Forni, S. Sarks, C.A. Harper, P. Allen, R. Buttery, C. McCarty, G. Morgan, S. Kirmani and S. Bhattacharya for sharing patients or DNA samples; L. Streb, R. Hockey, H. Haines, L. Affatigato, G. Beck, C. Taylor, S. Krob, G. Metthez, F. Ahmad, V. Buchillier, V. Kaltenrieder, R. McNeil and M. Cain for technical assistance; and C. Fasser for support of retinal degeneration research. Supported in part by NIH grants EY10539 and EY11515, the Carver Charitable Trust, The Ruth and Milton Steinbach Foundation, The Grousbeck Family Foundation, The Foundation Fighting Blindness, the Swiss National Science Foundation grant 32-053750.98, the Fondation Telethon Action Suisse, The Royal Victorian Institute for the Blind and an unrestricted grant from Research to Prevent Blindness.

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Authors and Affiliations

  1. The Department of Ophthalmology, The University of Iowa College of Medicine, Iowa City, USA
    Edwin M. Stone, Andrew J. Lotery, Kimberlie Vandenburgh & Gregory S. Hageman
  2. Hôpital Jules Gonin, Lausanne, Switzerland
    Francis L. Munier, Bertrand Piguet & Pascal Cousin
  3. Division de Génétique Médicale, CHUV, Lausanne, Switzerland
    Francis L. Munier & Daniel F. Schorderet
  4. The Department of Ophthalmology, University of Toronto, Toronto, Canada
    Elise Héon
  5. Eye Research Institute of Canada, Toronto , Canada
    Elise Héon
  6. Centre for Eye Research Australia, The University of Melbourne, Royal Victorian Eye and Ear Hospital, Victoria, Australia
    Robyn H. Guymer & David A. Mackey
  7. The Department of Pediatrics, The University of Iowa College of Medicine, Iowa City, Iowa, USA
    Darryl Nishimura, Ruth E. Swiderski & Val C. Sheffield
  8. The Department of Ophthalmology, Royal Victoria Hospital, Belfast, Northern Ireland
    Giuliana Silvestri
  9. Menzies Centre for Population Health Research, The University of Tasmania, Tasmania, Australia
    David A. Mackey
  10. The Institute of Ophthalmology, Moorfields Eye Hospital , London, England
    Alan C. Bird
  11. The Howard Hughes Medical Institute, University of Iowa, Iowa City, Iowa, USA
    Val C. Sheffield

Authors

  1. Edwin M. Stone
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  2. Andrew J. Lotery
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  3. Francis L. Munier
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  4. Elise Héon
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  5. Bertrand Piguet
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  6. Robyn H. Guymer
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  7. Kimberlie Vandenburgh
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  8. Pascal Cousin
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  9. Darryl Nishimura
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  10. Ruth E. Swiderski
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  11. Giuliana Silvestri
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  12. David A. Mackey
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  13. Gregory S. Hageman
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  14. Alan C. Bird
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  15. Val C. Sheffield
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  16. Daniel F. Schorderet
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Corresponding authors

Correspondence toEdwin M. Stone, Francis L. Munier or Val C. Sheffield.

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Stone, E., Lotery, A., Munier, F. et al. A single EFEMP1 mutation associated with both Malattia Leventinese and Doyne honeycomb retinal dystrophy.Nat Genet 22, 199–202 (1999). https://doi.org/10.1038/9722

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