title: Congenital myopathies: diseases of the actin cytoskeleton.
abstract: Congenital myopathies are clinical and genetic heterogeneous disorders characterized by skeletal muscle weakness ranging in severity. Three major forms have been identified: actin myopathy, intranuclear rod myopathy, and nemaline myopathy. Nemaline myopathy is the most common of these myopathies and is further subdivided into seven groups according to severity, progressiveness, and age of onset. At present, five genes have been linked to congenital myopathies. These include alpha-actin (ACTA1), alpha- and beta-tropomyosin (TPM3 and TPM2), troponin T (TNNT1), and nebulin (NEB). Their protein products are all components of the thin filament of the sarcomere. The mutations identified within these genes have varying impacts on protein structure and give rise to different forms of congenital myopathies. Greater understanding of muscle formation and cause of disease can be established through the study of the effect of mutations on the functional proteins. However, a major limitation in the understanding of congenital myopathies is the lack of correlation between the degree of sarcomeric disruption and disease severity. Consequently, great difficulty may be encountered when diagnosing patients and predicting the progression of the disorders. There are no existing cures for congenital myopathies, although improvements can be made to both the standard of living and the life expectancy of the patient through various therapies.
authors.affiliation: School of Biosciences, University of Birmingham, Birmingham, B15 2TT, UK.
authors.forename: Emilie
authors.initials: E
authors.lastname: Clarkson
authors.forename: Celine F
authors.initials: CF
authors.lastname: Costa
authors.forename: Laura M
authors.initials: LM
authors.lastname: Machesky
mesh_terms: D000199:Actins / Q000235:genetics* / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D006801:Humans; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009135:Muscular Diseases / Q000151:congenital* / Q000235:genetics / Q000503:physiopathology; D009154:Mutation; D010641:Phenotype; D014335:Tropomyosin / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D009124:Muscle Proteins; D014335:Tropomyosin; C035620:nebulin