Isolated cardiomyopathy caused by a DMD nonsense mutation in somatic mosaicism: genetic normalization in skeletal muscle
Article first published online: 13 DEC 2011
© 2011 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd
Volume 82, Issue 6, pages 574–578, December 2012
How to Cite
Juan-Mateu, J., Paradas, C., Olivé, M., Verdura, E., Rivas, E., González-Quereda, L., Rodríguez, M., Baiget, M. and Gallano, P. (2012), Isolated cardiomyopathy caused by a DMD nonsense mutation in somatic mosaicism: genetic normalization in skeletal muscle. Clinical Genetics, 82: 574–578. doi: 10.1111/j.1399-0004.2011.01814.x
- Issue published online: 6 NOV 2012
- Article first published online: 13 DEC 2011
- Accepted manuscript online: 17 NOV 2011 12:56PM EST
- Received 1 September 2011, revised and accepted for publication 14 November 2011
- dilated cardiomyopathy;
- genetic normalization;
- somatic mosaicism
Juan-Mateu J, Paradas C, Olivé M, Verdura E, Rivas E, González-Quereda L, Rodríguez MJ, Baiget M, Gallano P. Isolated cardiomyopathy caused by a DMD nonsense mutation in somatic mosaicism: genetic normalization in skeletal muscle.
X-linked dilated cardiomyopathy is a pure cardiac dystrophinopathy phenotype mainly caused by DMD mutations that present a specific transcription effect in cardiac tissue. We report a 26-year-old male who presented with severe dilated cardiomyopathy and high creatine kinase. The patient did not complain of skeletal muscle weakness. A muscle biopsy showed mild dystrophic changes and a low proportion of dystrophin-negative fibres. A molecular study identified a nonsense DMD mutation (p.Arg2098X) in somatic mosaicism. The ratio of mutant versus normal allele in blood and skeletal muscle suggests selective pressure against mutant muscle cells, a process known as genetic normalization. We hypothesize that this process may have mitigated skeletal muscle symptoms in this patient. This is the second report of a DMD somatic mosaic with evidence of genetic normalization in muscle. Somatic DMD mutations should be considered in patients presenting with idiopathic dilated cardiomyopathy.