Myopalladin in Dilated Cardiomyopathy and Limb Girdle Muscular Dystrophy

Limb girdle muscular dystrophy (LGMD) is a neuromuscular disorder caused by mutations in many different genes encoding components of the muscle fiber. Although a variety of causative genes have been identified, many cases with unknown cause remain. In a genetic screening of LGMD patients we recently identified three mutations in the heart and skeletal muscle protein MYPN, which was also recently shown to be involved in dilated cardiomyopathy (DCM). In the current study we will screen additional patients for MYPN gene mutations as well as study the role of MYPN and the identified mutations in heart and skeletal muscle based on the analysis of a mouse model in which MYPN has been deleted. To determine whether the identified mutations are causative for disease we will use a viral approach to express the mutations in MYPN deficient mice, allowing us to study the effect of the mutation in an animal model. Furthermore, we will test whether viral delivery of wildtype MYPN can rescue the effect of deletion of MYPN, which could form the basis for the development of a future gene therapy for the treatment of MYPN-based LGMD and DCM. Thus, our study fits well with Telethon's mission to treat rare genetic diseases.