These findings indicate that AAV-mediated cardiac transduction with microdystrophin might be a promising therapeutic strategy for the treatment of dystrophin-deficient cardiomyopathy.
Loss-of-function mutations in the genes encoding dystrophin and the associated membrane proteins, the sarcoglycans, produce muscular dystrophy and cardiomyopathy.
PLN-encoded phospholamban mutation in a large cohort of hypertrophic cardiomyopathy cases: summary of the literature and implications for genetic testing.
Duchenne muscular dystrophy (DMD), caused by mutations in the dystrophin gene, is associated with severe cardiac complications including cardiomyopathy and cardiac arrhythmias.
In addition, the cardiomyopathy related MYH6-A1004S and the MYBPC3-A833T mutations were also found in one and two unrelated subjects with ASDII, respectively.
Young males presenting with apparent isolated cardiomyopathy or acute myocarditis may harbor dystrophin mutations without overt skeletal muscle pathology.
In the present study a comprehensive analysis was made of mediators of the βAR pathway, myofilament properties and cardiac structure in patients with idiopathic (IDCM; n = 13) and ischemic (ISHD; n = 10) cardiomyopathy in comparison to non-failing hearts (donor; n = 10) for the following parameters: βAR density, G-coupled receptor kinases 2 and 5, stimulatory and inhibitory G-proteins, phosphorylation of myofilament targets of PKA, protein phosphatase 1, phospholamban, SERCA2a and single myocyte contractility.
In addition, our data suggest that a non-compaction phenotype is not required for the development of cardiomyopathy in this specific TNNT2 mutation leading to LVNC.
Recently, mutations in myosin heavy chain (MYH7), cardiac actin (ACTC), and troponin T (TNNT2) were associated with left ventricular noncompaction, a form of cardiomyopathy characterized with hypertrabeculation that may also include reduced function of the left ventricle.
Here, we describe a deletion of 25 bp in the gene encoding cardiac myosin binding protein C (MYBPC3) that is associated with heritable cardiomyopathies and an increased risk of heart failure in Indian populations (initial study OR = 5.3 (95% CI = 2.3-13), P = 2 x 10(-6); replication study OR = 8.59 (3.19-25.05), P = 3 x 10(-8); combined OR = 6.99 (3.68-13.57), P = 4 x 10(-11)) and that disrupts cardiomyocyte structure in vitro.
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.
The variant AF177763.1:g.203A>C (at position -36 bp relative to the PLN transcriptional start site) was found only in the heterozygous form in 1 out of 296 normal subjects and in 22 out of 381 cardiomyopathy patients (heart failure at age of 18-44 years, ejection fraction=22+/-9%).