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Genetic mapping of a second myotonic dystrophy locus

Nature Genetics volume 19, pages 196–198 (1998)Cite this article

Abstract

We report the mapping of a second myotonic dystrophy locus, myotonic dystrophy type 2 (DM2). Myotonic dystrophy (DM) is a multi-system disease and the most common form of muscular dystrophy in adults1. In 1992, DM was shown to be caused by an expanded CTG repeat in the 3´ untranslated region of the dystrophia myotonica-protein kinase gene (DMPK) on chromosome 19 (refs 2, 3, 4, 5, 6). Although several theories have been put forth to explain how the CTG expansion causes the broad spectrum of clinical features associated with DM, it is not understood how this mutation, which does not alter the protein-coding region of a gene, causes an affect at the cellular level7,8. We have identified a five-generation family (MN1) with a genetically distinct form of myotonic dystrophy. Affected members exhibit remarkable clinical similarity to DM (myotonia, proximal and distal limb weakness, frontal balding, cataracts and cardiac arrhythmias) but do not have the chromosome-19 CTG expansion. We have mapped the disease locus (DM2) of the MN1 family to a 10-cM region of chromosome 3q. Understanding the common molecular features of two different forms of the disease should shed light on the mechanisms responsible for the broad constellation of seemingly unrelated clinical features present in both diseases.

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Figure 1: Haplotype analysis for eight markers from the DM2 region of chromosome 3.
Figure 2: Schematic of the recombinant chromosomes from affected individuals that define the DM2 critical region.

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Acknowledgements

We thank family members for their participation, J. Lundgren for technical assistance and C. Peterson, C. Hauser and B. LeRoy for help with family history information and clinical visits. We are grateful to D. Weeks for his assistance with the SIMWALK2 program. This work was supported by the Graduate School of the University of Minnesota and by The National Institutes of Health (R01 NS35870).

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  1. Department of Neurology, University of Minnesota, Box 295 UMHC,420, Delaware St. SE., Minneapolis, 55455, Minnesota, USA

    Laura P. W. Ranum, Paul F. Rasmussen, Kellie A. Benzow, Michael D. Koob & John W. Day

  2. Institute of Human Genetics, University of Minnesota, Box 295 UMHC,420, Delaware St. SE., Minneapolis , 55455, Minnesota, USA

    Laura P. W. Ranum

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  1. Laura P. W. Ranum
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Correspondence to Laura P. W. Ranum.

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Ranum, L., Rasmussen, P., Benzow, K. et al. Genetic mapping of a second myotonic dystrophy locus. Nat Genet 19, 196–198 (1998). https://doi.org/10.1038/570

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