Dystrophin levels as low as 30% are sufficient to avoid muscular dystrophy in the human

Abstract

Mutations in the dystrophin gene give rise to Duchenne and Becker muscular dystrophies (DMD and BMD), in which both skeletal and cardiac muscles are affected, but also to X-linked dilated cardiomyopathy (XLDC), a condition characterised by exclusive cardiac involvement. XLDC patients with mutations at the 5' end of the gene typically have a cardiac specific severe transcriptional pathology, with absent dystrophin in the heart, while reduced levels of virtually normal dystrophin transcript and protein are present in the skeletal muscle. We now report the identification of a new XLDC family and the detailed characterisation of the levels of dystrophin protein present in skeletal muscle of this family, and of three previously studied XLDC families. We found that dystrophin levels comprised between 29% and 57% were sufficient to avoid muscle weakness in these XLDC families. This information will be of help for the development of therapeutic approaches aimed at restoring dystrophin levels sufficient to prevent the muscle pathology in DMD.