Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy (original) (raw)

Nature volume 355, pages 545–546 (1992)Cite this article

Abstract

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 _Eco_Rl 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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Author notes

  1. J. David Brook, Alan J. Buckler and David E. Housman: Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

Authors and Affiliations

  1. Institute of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, CF4 6EJ, UK
    Helen G. Harley, J. David Brook, Shelley A. Rundle, Stephen Crow, William Reardon, Alan J. Buckler, Peter S. Harper, David E. Housman & Duncan J. Shaw

Authors

  1. Helen G. Harley
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  2. J. David Brook
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  3. Shelley A. Rundle
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  4. Stephen Crow
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  5. William Reardon
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  6. Alan J. Buckler
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  7. Peter S. Harper
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  8. David E. Housman
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  9. Duncan J. Shaw
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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). https://doi.org/10.1038/355545a0

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