X-linked dilated cardiomyopathy is a pure cardiac dystrophinopathy phenotype mainly caused by DMD mutations that present a specific transcription effect in cardiac tissue.
Dystrophin localizes at the X chromosome, whose mutations might result in Duchenne muscular dystrophy, Becker muscular dystrophy and X-linked dilated cardiomyopathy.
The only known disease gene is the dystrophin gene causing X-linked dilated cardiomyopathy, but other cytoskeletal proteins, such as adhalin, could be involved.
Our report underlines the complexity of the pathogenic mechanism leading to X-linked dilated cardiomyopathy but suggests that differences in tissue-specific expression of dystrophin mutations may be a common feature in this condition.
Dystrophin has been identified as the gene responsible for X-linked dilated cardiomyopathy and this protein, which is also responsible for Duchenne and Becker muscular dystrophy, plays an important role in myocyte and cardiomyocyte function.
Mutations in the DMD gene, encoding the dystrophin protein, are responsible for the dystrophinopathies Duchenne Muscular Dystrophy (DMD), Becker Muscular Dystrophy (BMD), and X-linked Dilated Cardiomyopathy (XLDC).
X-linked dilated cardiomyopathy (XLCM) was first described in 1987 and associated with dystrophin gene (DMD) mutations a decade later in one of the original two families.
We analyzed 78 BMD and X-linked dilated cardiomyopathy patients with common deletion mutations predicted to alter the dystrophin protein and correlated their mutations to cardiomyopathy age of onset.
X linked dilated cardiomyopathy is a familial disease that is allelic to Duchenne and Becker muscular dystrophies and caused by mutations in the dystrophin gene.
Molecular genetic studies have delineated the gene for BTHS, which maps to distal Xq28, from the gene for so called X linked dilated cardiomyopathy (XLCM), a teenage onset dilated cardiomyopathy, recently mapped to the 5' portion of the dystrophin locus at Xp21.
A functional role for these sequences was suggested by a pure intronic DMD deletion causing X-linked dilated cardiomyopathy through the prevalent cardiac incorporation of the aberrant pseudo-exon, marked as Alu-exon, into the dystrophin transcript.
Dystrophin muscle enhancer 1 is implicated in the activation of non-muscle isoforms in the skeletal muscle of patients with X-linked dilated cardiomyopathy.
Despite promoter tissue specificity, up-regulation of the brain and Purkinje cell type dystrophin isoforms was described in skeletal muscle of X-linked dilated cardiomyopathy (XLDCM) and BMD affected individuals.