Missense mutations in desmin associated with familial cardiac and skeletal myopathy (original) (raw)

Nature Genetics volume 19, pages 402–403 (1998)Cite this article

Abstract

Desmin-related myopathy (OMIM 601419) is a familial disorder characterized by skeletal muscle weakness associated with cardiac conduction blocks, arrhythmias and restrictive heart failure, and by intracytoplasmic accumulation of desmin-reactive deposits in cardiac and skeletal muscle cells1,[2](/articles/ng0898%5F402#ref-CR2 "Goebel, H.H., Muller, J., Gillen, H.W. & Merritt, A.D. Autosomal dominant "spheroid body myopathy". Muscle Nerve 1, 14–26 (1978)."),3,4. The underlying molecular mechanisms are unknown. Involvement of the desmin gene (DES) has been excluded in three families diagnosed with desmin-related myopathy5. We report two new families with desmin-related cardioskeletal myopathy associated with mutations in the highly conserved carboxy-terminal end of the desmin rod domain. A heterozygous A337P mutation was identified in a family with an adult-onset skeletal myopathy and mild cardiac involvement. Compound heterozygosity for two other mutations, A360P and N393I, was detected in a second family characterized by childhood-onset aggressive course of cardiac and skeletal myopathy.

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References

  1. Fardeau, M. et al. Une nouvelle affection musculaire familiale, definie par l'accumulation intra-sarcoplasmique d'un materiel granulofilamentaire dense en microscopie electronique. Rev. Neurol. (Paris) 134, 411–425 (1978).
    CAS Google Scholar
  2. Goebel, H.H., Muller, J., Gillen, H.W. & Merritt, A.D. Autosomal dominant "spheroid body myopathy". Muscle Nerve 1, 14–26 (1978).
    Article CAS Google Scholar
  3. Horowitz, S.H. & Schmalbruch, H. Autosomal dominant distal myopathy with desmin storage: a clinicopathologic and electrophysiologic study of a large kinship. Muscle Nerve 17, 151– 160 (1994).
    Article CAS Google Scholar
  4. Goebel, H.H. Desmin-related neuromuscular disorders. Muscle Nerve 18, 1306–1320 (1995).
    Article CAS Google Scholar
  5. Vicart, P. et al. Human desmin gene: cDNA sequence, regional localization and exclusion of the locus in a familial desmin-related myopathy. Hum. Genet. 98, 422–429 (1996).
    Article CAS Google Scholar
  6. Fuchs, E. & Weber, K. Intermediate filaments: structure, dynamics, function, and disease. Annu. Rev. Biochem. 63, 345–382 (1994).
    Article CAS Google Scholar
  7. Raats, J.M. et al. Assembly of carboxy-terminally deleted desmin in vimentin-free cells. Eur. J. Cell Biol. 56, 84–103 (1991).
    CAS PubMed Google Scholar
  8. Raats, J.M. et al. Muscle-specific expression of a dominant negative desmin mutant in transgenic mice. Eur. J. Cell Biol. 71, 221– 236 (1996).
    CAS PubMed Google Scholar
  9. Yu, K.R. et al. Truncated desmin in PtK2 cells induces desmin-vimentin-cytokeratin coprecipitation, involution of intermediate filament networks, and nuclear fragmentation: a model for many degenerative diseases. Proc. Natl Acad. Sci. USA 91, 2497–2501 ( 1994).
    Article CAS Google Scholar
  10. Letai, A., Coulombe, P.A. & Fuchs, E. Do ends justify the mean? Proline mutations at the ends of the keratin coiled-coil rod segment are more disruptive than internal mutations. J. Cell Biol. 116, 1181–1195 ( 1992).
    Article CAS Google Scholar
  11. Nakano, S., Engel, A.G., Waclawik, A.J., Emslie-Smith, A.M. & Busis, N.A. Myofibrillar myopathy with abnormal foci of desmin positivity. 1.Light and electron microscopy analysis of 10 cases. J. Neuropathol. Exp. Neurol. 55, 549– 562 (1996).
    Article CAS Google Scholar

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Acknowledgements

The authors are grateful to the members of affected families for participation in this study. We are also grateful to S. A. Smith and C. Johnson of the University of Minnesota for sharing study results and biopsy materials of the CSM2 family.

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Authors and Affiliations

  1. Medical Neurology Branch, Bethesda, 20892, Maryland, USA
    Lev G. Goldfarb, Kye-Yoon Park, Svetlana Gorokhova, Hee-Suk Lee, Olavo Vasconcelos, James W. Nagle, Christina Semino-Mora, Kumaraswamy Sivakumar & Marinos C. Dalakas
  2. Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, 20892, Maryland, USA
    Larisa Cervenáková & Svetlana Gorokhova
  3. American Red Cross J.H. Holland Laboratory, Rockville, 20855, Maryland, USA
    Larisa Cervenáková
  4. Barrow Neurological Institute, Phoenix, 85013, Arizona, USA
    Kumaraswamy Sivakumar

Authors

  1. Lev G. Goldfarb
  2. Kye-Yoon Park
  3. Larisa Cervenáková
  4. Svetlana Gorokhova
  5. Hee-Suk Lee
  6. Olavo Vasconcelos
  7. James W. Nagle
  8. Christina Semino-Mora
  9. Kumaraswamy Sivakumar
  10. Marinos C. Dalakas

Corresponding author

Correspondence toLev G. Goldfarb.

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Goldfarb, L., Park, KY., Cervenáková, L. et al. Missense mutations in desmin associated with familial cardiac and skeletal myopathy.Nat Genet 19, 402–403 (1998). https://doi.org/10.1038/1300

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