Heart involvement in muscular dystrophies due to sarcoglycan gene mutations

Abstract

Mutations in the sarcoglycan genes cause autosomal‐recessive muscular dystrophies. Because sarcoglycan genes and their protein products are highly expressed both in skeletal and cardiac muscle, patients with these mutations might be expected to be at risk to develop dilated cardiomyopathy. We therefore studied 13 patients with α‐, β‐, γ‐sarcoglycan gene mutations by thorough cardiological assessment. Electrocardiographic or echocardiographic abnormalities were observed in about 30% of cases showing a severe course of muscular dystrophy. No correlation was found between the presence of cardiac abnormalities and the type of mutation or sarcoglycan gene involved. The cardiac involvement was never severe, but it may be detected in early stages of the muscle disease. The absence of overt cardiac dysfunction may be due to lower sarcoglycan protein expression in cardiac than skeletal muscle or to less sarcolemmal instability at the myocardial level, possibly related to the different distribution of forces generated by contraction of the myocardium with respect to proximal limb‐girdle muscles. © 1999 John Wiley & Sons, Inc. Muscle Nerve 22: 473–479, 1999.

The genetic and molecular basis of muscular dystrophy: roles of cell–matrix linkage in the pathogenesis

“…Using animal models and virus-gene transfer techniques, it has been demonstrated that genetic deficiencies of the SG complex can be corrected in vivo Durbeej et al 2003). Inherited cardiomyopathy can be associated with genetic defects in the DGC (Towbin 1998), and a correlation between the primary mutation of the SG gene and cardiomyopathy has been established (Melacini et al 1999). Accordingly, the genetically engineered models of b-SG and d-SG-null mice developed cardiomyopathy (Coral-Vasquez et al 1999;Durbeej et al 2000).…”

Alterations in Dystrophin-Related Glycoproteins in Development of Right Ventricular Failure in Rats

“…Genetic defects of sarcoglycans, dystroglycan, and/or dystrophin are believed to play an important role in the development of muscular diseases such as cardiomyopathy and muscular dystrophies (6,7,29,30). However, whether or not there is a substantial contribution of alterations in the DRGP complex of the heart without genetic mutation to the development of heart failure remains unclear.…”

“…Inherent mutation or depletion of sarcoglycans and/or dystrophin genes causes muscular dystrophy and dilated cardiomyopathy in humans and hamsters (6,7). Recent studies have shown that δ-sarcoglycan gene transfection mediated by adeno-associated virus improves cardiac function, sarcolemmal stability, and survival of TO-2 hamsters (8), which are an animal model mimicking human dilated cardiomyopathy.…”

PKC Proteins and Muscular Dystrophy

“…Conduction defects have been evidenced in Duchenne muscular dystrophy [41,42], Becker muscular dystrophy [43,44], myotonic dystrophy type 1 and 2 [45,46], Emery-Dreifuss muscular dystrophy [47], and limb girdle muscular dystrophy [48,49].…”