How to cite this article: Kesari A, Neel R, Wagoner L, Harmon B, Spurney C, Hoffman EP. 2009. Somatic mosaicism for Duchenne dystrophy: Evidence for genetic normalization mitigating muscle symptoms. Am J Med Genet Part A 149A:1499–1503.
Somatic mosaicism for Duchenne dystrophy: Evidence for genetic normalization mitigating muscle symptoms†
Version of Record online: 15 JUN 2009
Copyright © 2009 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 149A, Issue 7, pages 1499–1503, July 2009
How to Cite
Kesari, A., Neel, R., Wagoner, L., Harmon, B., Spurney, C. and Hoffman, E. P. (2009), Somatic mosaicism for Duchenne dystrophy: Evidence for genetic normalization mitigating muscle symptoms. Am. J. Med. Genet., 149A: 1499–1503. doi: 10.1002/ajmg.a.32891
- Issue online: 18 JUN 2009
- Version of Record online: 15 JUN 2009
- Manuscript Accepted: 18 MAR 2009
- Manuscript Received: 12 FEB 2009
- NIH. Grant Numbers: 3R01 NS29525, 5R24HD050846, 1P30HD40677
- genetic normalization;
- somatic mosaic;
We describe a young adult male presenting with cardiac failure necessitating cardiac transplantation 7 months after presentation. Skeletal muscle biopsy showed mosaic immunostaining for dystrophin. DNA studies showed somatic mosaicism for a nonsense mutation in the dystrophin gene (Arg2905X). The frequency of normal versus mutant genes were determined in blood/DNA (50:50), muscle/DNA (80:20) and muscle/mRNA (90:10). These data are consistent with genetic normalization processes that may biochemically rescue skeletal muscle in male somatic mosaic patients mitigating muscle symptoms (gradual loss of dystrophin-negative skeletal muscle tissue replaced by dystrophin-positive stem cells). To our knowledge, this is only the second reported case of a clinically ascertained patient showing somatic mosaicism for Duchenne muscular dystrophy (DMD). We hypothesize that many somatic mosaic males for DMD exist, yet they are not detected clinically due to genetic normalization. Somatic mosaicism for DMD should be considered in acute heart failure with dilated cardiomyopathy, as genetic normalization in heart is unlikely to occur. © 2009 Wiley-Liss, Inc.