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Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy


MYOTONIC Received 2 December 1991; accepted 7 January 1992. dystrophy is the commonest adult form of muscular dystrophy, with an estimated incidence of 1 per 7,500, although this is likely to be an underestimate because of the difficulty of detecting minimally affected individuals. It is a multisystem autosomal dominant disorder of unknown biochemical basis1. No case of new mutation has been proven. We have isolated a human genomic clone that detects novel restriction fragments specific to individuals with myotonic dystrophy. A two-allele EcoRl polymorphism is seen in normal individuals, but in most affected individuals one of the normal alleles is replaced by a larger fragment, which varies in length both between unrelated affected individuals and within families. The unstable nature of this region may explain the characteristic variation in severity and age at onset of the disease. A second polymorphism at this locus is in almost complete linkage disequilibrium with myotonic dystrophy, strongly supporting our earlier results which indicated that most cases are descended from one original mutation2.

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  1. Harper, P. S. Myotonic Dystrophy 2nd edn (Saunders, London and Philadelphia, 1989).

    Google Scholar 

  2. Harley, H. G. et al. Am. J. hum. Genet. 49, 68–75 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Harper, P. S. & Dyken, P. R. Lancet ii, 53–55 (1972).

    Article  Google Scholar 

  4. Penrose, L. S. Ann. Eugen. 14, 125–132 (1948).

    Article  CAS  Google Scholar 

  5. Howeler, C. J., Busch, H. F. M., Geraedts, J. P. M., Niermeijer, M. F. & Staal, A. Brain 112, 779–797 (1989).

    Article  Google Scholar 

  6. Monaco, A. P. et al. Nature 323, 646–650 (1986).

    Article  ADS  CAS  Google Scholar 

  7. Wallace, M. R. et al. Science 249, 181–186 (1990).

    Article  ADS  CAS  Google Scholar 

  8. Cawthorn, R. M. et al. Cell 62, 193–201 (1990).

    Article  Google Scholar 

  9. Verkerk, A. J. M. H. et al. Cell 65, 905–914 (1991).

    Article  CAS  Google Scholar 

  10. Oberle, I. et al. Science 252, 1097–1102 (1991).

    Article  ADS  CAS  Google Scholar 

  11. Yu, S. et al. Science 252, 1179–1181 (1991).

    Article  ADS  CAS  Google Scholar 

  12. Johnson, K. J. et al. Am. J. hum. Genet. 46, 1073–1081 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Shutler, G. et al. Genomics 9, 500–504 (1991).

    Article  CAS  Google Scholar 

  14. Thibault, M.-C. et al. Cytogenet. Cell Genet. (in the press).

  15. Jansen, G. et al. Am. J. hum. Genet. 49 (suppl.), 82 (1991).

    Google Scholar 

  16. Smeets, H. J. M., Hermens, R., Brunner, H. G., Ropers, H.-H. & Wieringa, B. Genomics 9, 257–263 (1991).

    Article  CAS  Google Scholar 

  17. Harley, H. G. et al. Hum. Genet. 87, 73–80 (1991).

    Article  CAS  Google Scholar 

  18. Fu, Y.-H. et al. Cell 67, 1–20 (1991).

    Article  Google Scholar 

  19. La Spada, A. R., Wilson, E. M., Lubahn, D. B., Harding, A. E. & Fischbeck, K. H. Nature 352, 77–79 (1991).

    Article  ADS  CAS  Google Scholar 

  20. Sutherland, G. R. et al. Lancet 338, 289–292 (1991).

    Article  CAS  Google Scholar 

  21. Buxton, J. et al. Nature 355, 547–548 (1992).

    Article  ADS  CAS  Google Scholar 

  22. Yule, G. U. & Kendall, M. G. An Introduction to the Theory of Statistics 14th edn (Griffin, London, 1968).

    MATH  Google Scholar 

  23. Sambrook, J., Fritsch, E. F. & Maniatis, T. Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Press, New York, 1989).

    Google Scholar 

  24. Richards, R. I. et al. J. med. Genet. 28, 818–823 (1991).

    Article  CAS  Google Scholar 

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Harley, H., Brook, J., Rundle, S. et al. Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy. Nature 355, 545–546 (1992).

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