Skip to main content

Thank you for visiting nature.com. 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.

Very mild muscular dystrophy associated with the deletion of 46% of dystrophin

Abstract

DUCHENNE muscular dystrophy (DMD)1 and Becker muscular dystrophy (BMD), a much milder form of the disease where the age of onset can sometimes be as late as the third or fourth decade of life, are caused by mutations in the same X-linked gene2–7, a 14 kilobase (kb) transcript6,7which is spread over more than 2 megabases of the human X chromosome8–10. The corresponding protein, dystrophin, has a relative molecular mass of 400,000 (ref. 11). Most mutations causing DMD and BMD are deleá-tions7,12,13 (reviewed in ref. 14) and deletions associated with both phenotypes are observed throughout the gene sequence. This observation led to the suggestion15 that DMD patients possess deletions that disrupt the reading frame of the protein, whereas BMD patients have deletions that retain the translational reading frame and enable the muscle cells to produce altered dystrophin products. This theory is supported by immunoblotting studies, which show that DMD patients lack dystrophin in their muscle cells or that dystrophin is present at very low levels, whereas BMD patients produce a protein with reduced abundance or abnormal size16. Here we describe a deletion of the dystrophin gene in a family segregating for very mild BMD, one member of which was still ambulant at age 61 years, which removes a central part of the dystrophin gene encompassing 5,106 base pairs of coding sequence, almost half the coding information. Immunological analysis of muscle from one of the patients demonstrates that this mutation results in the production of a truncated polypeptide localized correctly in the muscle cell. These results are particularly significant in the context of gene therapy which, if it is ever envisaged, would be facilitated by the replacement of the very large dystrophin gene with a more manipulatable mini-gene construct.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

References

  1. Emery, A. E. H. Duchenne Muscular Dystrophy (eds. Harper, P. & Bobrow, M) (Oxford University Press, 1987).

    Google Scholar 

  2. Davies, K. E. et al. Nucleic Acids Res. 11, 2302–2312 (1983).

    ADS  Article  Google Scholar 

  3. Kingston, H. M. et al. Lancet 2, 1200 (1983).

    CAS  Article  Google Scholar 

  4. Kunkel, L. M. et al. Nature 322, 73–77 (1986).

    ADS  CAS  Article  Google Scholar 

  5. Monaco, A. P. et al. Nature 316, 842–845 (1985).

    ADS  CAS  Article  Google Scholar 

  6. Ray, P. N. et al. Nature 318, 672–675 (1985).

    ADS  CAS  Article  Google Scholar 

  7. Koenig, M. et al. Cell 50, 509–517 (1987).

    CAS  Article  Google Scholar 

  8. Burmeister, M. & Lehrach, H. Nature 324, 582–585 (1986).

    ADS  CAS  Article  Google Scholar 

  9. van Ommen, G.-J. B. et al. Cell 47, 499–504 (1986).

    CAS  Article  Google Scholar 

  10. Kenwrick, S. et al. Cell 48, 351–357 (1987).

    CAS  Article  Google Scholar 

  11. Hoffman, E. P., Brown, R. H. & Kunkel, L. M. Cell 51, 919–928 (1987).

    CAS  Article  Google Scholar 

  12. Forrest, S. M. et al. Nature 329, 638–640 (1987).

    ADS  CAS  Article  Google Scholar 

  13. Darras, B. T. & Francke, U. Am. J. hum. Genet. 43, 612–619 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Love, D. R. & Davies, K. E. Molec biol. Med. 6, 7–17 (1989).

    CAS  PubMed  Google Scholar 

  15. Monaco, A. P. et al. Genomics 2, 90–95 (1988).

    CAS  Article  Google Scholar 

  16. Hoffman, E. P. et al. N. Engl J. Med. 318, 1363–1368 (1988).

    CAS  Article  Google Scholar 

  17. Davies, K. E. et al. J. Med. Genet. 99, 99 (1987).

    ADS  Google Scholar 

  18. Smith, T. J., Forrest, S. M., Cross, G. S. & Davies, K. E. Nucleic Acids Res. 15, 9761–9769 (1987).

    CAS  Article  Google Scholar 

  19. Forrest, S. M. et al. Genomics 2, 109–114 (1988).

    CAS  Article  Google Scholar 

  20. Koenig, M., et al. Am. J. hum. Genet. 45, 498–506 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Den Dunnen, J. T. Am. J. hum. Genet, in the press.

  22. Nicholson, L. V. B. et al. J. neurol. Sci. 94, 125–136 (1989).

    CAS  Article  Google Scholar 

  23. Nicholson, L. V. B. et al. J. neurol. Sci. 94, 137–146 (1989).

    CAS  Article  Google Scholar 

  24. Zubrzycka-Gaarn, E. E. et al. Nature 333, 466–469 (1988).

    ADS  CAS  Article  Google Scholar 

  25. Watkins, S. C., Hoffman, E. P., Slayter, H. S. & Kunkel, L. M. Nature 333, 863–866 (1988).

    ADS  CAS  Article  Google Scholar 

  26. Love, D. R. et al. Nature 339, 55–58 (1989).

    ADS  CAS  Article  Google Scholar 

  27. Davison, M. D. & Critchley, D. R. Cell 52, 159–160 (1988).

    CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

England, S., Nicholson, L., Johnson, M. et al. Very mild muscular dystrophy associated with the deletion of 46% of dystrophin. Nature 343, 180–182 (1990). https://doi.org/10.1038/343180a0

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/343180a0

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

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