Muscle fiber deterioration resulting in progressive skeletal muscle weakness, heart failure, and respiratory distress occurs in more than 20 inherited myopathies. As discussed in this Review, one of the newly identified myopathies is desminopathy, a disease caused by dysfunctional mutations in desmin, a type III intermediate filament protein, or αB-crystallin, a chaperone for desmin. The range of clinical manifestations in patients with desminopathy is wide and may overlap with those observed in individuals with other myopathies. Awareness of this disease needs to be heightened, diagnostic criteria reliably outlined, and molecular testing readily available; this would ensure prevention of sudden death from cardiac arrhythmias and other complications.
Lev G. Goldfarb, Marinos C. Dalakas
Molecular cytoarchitecture of a myocyte, featuring proteins involved in skeletal and cardiac myopathies.
Desmin is the main muscle IF protein. It interacts with other proteins to support myofibrils at the level of the Z disc and forms a continuous cytoskeletal IF network that maintains a spatial relationship between the contractile apparatus and other structural elements of the cell. Desmin provides maintenance of cellular integrity, force transmission, and mechanochemical signaling. Mutations in other sarcomeric and cytoskeletal proteins (plectin, myotilin, filamin C, αB-crystallin, Z band alternatively spliced PDZ-motif protein [ZASP], and BCL2-associated athanogene 3 [BAG3]) cause neuromuscular disorders. Adapted with permission from