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 cells1,2,3,4. 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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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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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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DOI: https://doi.org/10.1038/1300
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