Surplus protein myopathies

Certain muscular dystrophies are marked by absence or reduction of mutant proteins, foremost dystrophinopathies and sarcoglycanopathies. Conversely, other sporadic and familial neuromuscular conditions are marked by a surplus of proteins present in a granular or filamentous form, such as desmin-related myopathies, actinopathy and, perhaps, hyaline body myopathy. This emerging group of congenital myopathies is clinically, immunohistochemically, and genetically diverse. Clinically, early- and late-onset diseases with variable courses are described. Immunohistochemically, mutant gene-related and other proteins have been identified by immunohistochemistry. Mutations in the desmin and alpha-B crystallin genes have been discovered in desminopathies. Mutations in the actin gene, but in no other genes have been revealed in actinopathy. Surplus sarcoplasmic and/or intranuclear nemaline bodies have been related to mutant tropomyosin-3, actin and nebulin genes. This emerging concept of surplus protein myopathies will require substantial investigation to further interpret the results of present and future studies.