Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Butterfly–shaped pigment dystrophy of the fovea caused by a point mutation in codon 167 of the RDS gene


Butterfly–shaped pigment dystrophy of the fovea is an autosomal dominant eye disease characterized by a bilateral accumulation of yellowish or pigmented material at the level of the retinal pigment epithelium. It shares some clinical and histopathologic features with age related macular degeneration which is the most common cause of legal blindness in older patients. We screened affected patients from a three generation family with butterfly dystrophy for mutations in candidate genes. A base substitution was identified in the peripherin (RDS) gene and DMA sequencing revealed a G to A transition in codon 167 that substitutes aspartic acid for a highly conserved glycine. The mutation segregates with the disease phenotype (Zmax = 4, Θ = 0) strongly suggesting that it causes the macular disease in this family.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Deutman, A.F., van Blommestein, J.D.A., Henkes, H.E., Waardenburg, P.J. & Solleveld-van Driest, E. Butterfly-shaped pigment dystrophy of the fovea. Arch. Ophthalmol. 83, 558–569 (1970).

    CAS  Article  Google Scholar 

  2. 2

    Gass, J.D.M. A clinicopathologic study of a peculiar faveomacular dystrophy. Trans. Am. Ophth. Soc. 72, 139–155 (1974).

    CAS  Google Scholar 

  3. 3

    Marmor, M.F. & Byers, B. Pattern dystrophy of the pigment epithelium. Am. J. Ophthalmol. 84, 32–44 (1977).

    CAS  Article  Google Scholar 

  4. 4

    Hsieh, R.C., Fine, B.S. & Lyons, J.S. Patterned dystrophies of the retinal pigment epithelium. Arch. Ophthalmol. 95, 429–435 (1977).

    CAS  Article  Google Scholar 

  5. 5

    de Jong, P.T.V.M. & Delleman, J.W. Pigment epithelial pattern dystrophy: Four different manifestations in a family. Arch. Ophthalmol. 100, 1416–1421 (1982).

    CAS  Article  Google Scholar 

  6. 6

    Watzke, R.C., Folk, J.C. & Lang, R.M. Pattern dystrophy of the retinal pigment epithelium. Ophthalmology. 89, 1400–1406 (1982).

    CAS  Article  Google Scholar 

  7. 7

    McKusick, V.A. Mendelian Inheritance in Man 9th edn (Johns Hopkins University, Baltimore, 1990).

    Google Scholar 

  8. 8

    Liebowitz, H.M., Krueger, D.E. & Maunder, L.R. The Framingham eye study. Surv. Ophthalmol. 24 (suppl) 335–610 (1980).

    Article  Google Scholar 

  9. 9

    Molday, R.S., Hicks, D. & Molday, L.Peripherin. A rim-specific membrane protein of rod outer segment discs. Invest. Ophthalmol. Vis. Sci. 28, 50–61 (1987).

    CAS  PubMed  Google Scholar 

  10. 10

    Travis, G.H., Brennan, M.B., Danielson, P.E., Kozak, C.A. & Sutcliffe, J.G. Identification of a photoreceptor-specific mRNA encoded by the gene responsible for retinal degeneration slow (rds). Nature 338, 70–73 (1989).

    CAS  Article  Google Scholar 

  11. 11

    Connell, G., Bascom, R., Molday, L., Reid, D., McInnes, R.R. & Molday, R.S. Photoreceptor peripherin is the normal product of the gene responsible for retinal degeneration in the rds mouse. Proc. natn. Acad. Sci. U.S.A. 88, 723–726 (1991).

    CAS  Article  Google Scholar 

  12. 12

    Travis, G.H. et al. The human retinal degeneration slow (RDS) gene: Chromosome assignment and structure of the mRNA. Genomics 10, 733–739 (1991).

    CAS  Article  Google Scholar 

  13. 13

    Farrar, J.F. et al. A three-base-pair deletion in the peripherin-RDS gene in one form of retinitis pigmentosa. Nature 354, 478–480 (1991).

    CAS  Article  Google Scholar 

  14. 14

    Kajiwara, K. et al. Mutations in the human retinal degeneration slow gene in autosomal dominant retinitis pigmentosa. Nature 354, 480–483 (1991).

    CAS  Article  Google Scholar 

  15. 15

    Kajiwara, K., Hahn, L.B., Mukai, S., Berson, E.L. & Dryja, T.P. Mutations in the human RDS gene in patients with autosomal dominant retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci. (Suppl). 33/4, 1396 (1992).

    Google Scholar 

  16. 16

    Meyers, R.M., Fischer, S.G., Lerman, L.S. & Maniatis, T. Nearly all single base substitutions in DNA fragments joined to a GC-clamp can be detected by denaturing gradient gel electrophoresis. Nucl. Acids Res. 13, 3131–3145 (1985).

    Article  Google Scholar 

  17. 17

    Sheffield, V.C., Cox, D.R., Myers, R.M. Attachment of a 40-base-pair G+C−rich sequence (GC-clamp) to genomic DNA fragments by the polymerase chain reaction results in improved detection of single-base changes. Proc. natn. Acad. Sci. U.S.A. 86, 232–236 (1989).

    CAS  Article  Google Scholar 

  18. 18

    Sheffield, V.C. et al. Detection of multiallele polymorphisms within gene sequences by GC-clamped denaturing gradient gel electrophoresis. Am. J. hum. Genet. 50, 567–575 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 19

    Sheffield, V.C., Fishman, G.A., Beck, J.S., Kimura, A.E. & Stone, E.M. Identification of novel rhodopsin mutations associated with retinitis pigmentosa by GC-clamped denaturing gradient gel electrophoresis. Am. J. hum. Genet. 49, 699–706 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20

    Polymeropoulos, M.H., Xiao, H., Rath, D.S. & Merril, C.R. Tetranucleotide repeat polymorphism at the human dihydrofolate reductase psi-2 pseudogene (DHFRP2). Nucl. Acids Res. 19, 4792 (1991).

    PubMed  Google Scholar 

  21. 21

    Kumar-Singh, R., Jordan, S.A., Farrar, G.J. & Humphries, P. Poly (TYA) polymorphism at the human retinal degeneration slow (RDS) locus. Nucl.Acids Res. 19, 5800 (1991).

    CAS  Article  Google Scholar 

  22. 22

    Gass, J.D.M. Stereoscopic Atlas of Macular Diseases. 60–91 (C.V. Mosby, St. Louis, 1987).

  23. 23

    Pearce, W.G. Doyne's honeycomb retinal degeneration. Clinical and genetic features. Br. J. Ophthalmol. 52, 73–78 (1968).

    CAS  Article  Google Scholar 

  24. 24

    Deutman, A.F. & Jansen, L.M.A.A. Dominantly inherited drusen of Bruch's membrane. Br. J. Ophthalmol. 54, 373–382 (1970).

    CAS  Article  Google Scholar 

  25. 25

    Hyman, L.G., Lilienfeld, A.M., Ferris, F.L. & Fine, S.L. Senile macular degeneration: A case-control study. Am. J. Epidemiol. 118, 213–227 (1983).

    CAS  Article  Google Scholar 

  26. 26

    Meyers, S.M. & Zachary, A.A. Monozygotic twins with age-related macular degeneration. Arch. Ophthalmol. 106, 651–653 (1988).

    CAS  Article  Google Scholar 

  27. 27

    Melrose, M.A., Magaragal, L.E. & Lucier, A.C. Identical twins with subretinal neovascularization complicating senile macular degeneration. Ophthal. Surg. 16, 648–651 (1985).

    CAS  Google Scholar 

  28. 28

    Stone, E.M., Nichols, B.E., Streb, L.M., Kimura, A.E. & Sheffield, V.C. Genetic linkage of vitelliform macular degeneration (Best's disease) to chromosome 11q13. Nature Genet. 1, 246–250 (1992).

    CAS  Article  Google Scholar 

  29. 29

    Bascom, R.A. et al. Cloning of the cDNA for a novel photoreceptor membrane protein (rom-1) identifies a disk rim protein family implicated in human retinopathies. Neuron 8, 1171–1184 (1992).

    CAS  Article  Google Scholar 

  30. 30

    Connell, G.J. & Molday, R.S. Molecular cloning, primary structure, and orientation of the vertebrate photoreceptor cell protein peripherin in the rod outer segment disk membrane. Biochemistry 29, 4691–4698 (1990).

    CAS  Article  Google Scholar 

  31. 31

    Hawkins, R.K., Jansen, H.G. & Sanyal, S. Development and degeneration of retina in rds mutant mice: Photoreceptor abnormalities in the heterozygotes. Exp. Eye Res. 41, 701–720 (1985).

    CAS  Article  Google Scholar 

  32. 32

    Jansen, H.G. & Sanyal, S. Development and degeneration of retina in rds mutant mice: Electron microscopy. J. comp. Neurol. 224, 71–84 (1984).

    CAS  Article  Google Scholar 

  33. 33

    Nathans, J. et al. Molecular genetics of human blue cone monochromacy. Science 245, 831–838 (1989).

    CAS  Article  Google Scholar 

  34. 34

    Reichel, E., Bruce, A.M., & Berson, E.L. An electroretinographic and molecular genetic study of X-linked cone degeneration. Am. J. Ophthalmol. 108, 540–547 (1989).

    CAS  Article  Google Scholar 

  35. 35

    Grimberg, J. et al. A simple and efficient non-organic procedure for the isolation of genomic DNA from blood. Nucl. Acids Res. 17, 8390 (1989).

    CAS  Article  Google Scholar 

  36. 36

    Nichols, B.E., Stone, E.M. & Sheffield, V.C. A user-friendly Macintosh interface for DOS-based linkage analysis. Am. J. hum. Genet. (Suppl.) (in the press).

  37. 37

    Lathrop, G.M. & Lalouel, J.M. Easy calculations of lod scores and genetic risks on small computers. Am. J. hum. Genet. 36, 460–465 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information



Rights and permissions

Reprints and Permissions

About this article

Cite this article

Nichols, B., Sheffield, V., Vandenburgh, K. et al. Butterfly–shaped pigment dystrophy of the fovea caused by a point mutation in codon 167 of the RDS gene. Nat Genet 3, 202–207 (1993).

Download citation

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing