Assessment of the molecular consequences associated with loss of dysferlin expression in hiPSC-derived muscle cells from LGMD R2 patients.

LGMD R2 is a rare genetic disorder characterized by progressive proximal muscle weakness and wasting caused by a recessive loss of function of dysferlin, a transmembrane protein controlling plasma membrane repair in skeletal muscles. Despite major advances in biotherapies in recent years, there is currently no curative treatment available for LGMD R2, or dysferlinopathies in general. This failure can be explained in part by our lack of understanding of the functions performed by dysferlin within the muscle fiber. Indeed, despite the identification of dysferlin's role in membrane repair, intracellular vesicular trafficking or calcium homeostasis, we do not know which of these functions or combination of functions is most involved in the pathophysiological development of dysferlinopathies. It also seems highly likely that other dysferlin functions have yet to be discovered. In this aim, we generated hiPSC-derived skeletal muscle model and investigated the molecular consequences associated with loss of dysferlin expression by performing a comparative gene expression profiling between control and LGMD R2 myotubes.