title: Skeletal muscle disease due to mutations in tropomyosin, troponin and cofilin.
abstract: Tropomyosin (Tm) and the troponins (troponin I, troponin T and troponin C) are proteins that work cooperatively to regulate muscle contraction, making actin-myosin interactions sensitive to cytosolic calcium levels. Several isoforms exist for each component in this group, each having a specific expression pattern that enables cardiac, slow skeletal (type 1) and fast skeletal (type 2) muscle fibers to have distinct contractile properties. Mutations in all components of this complex have been associated with skeletal muscle disease. The first disease associations were with nemaline myopathy, but recently other congenital myopathies ('cap disease', congenital fiber type disproportion) and other clinical entities (distal arthrogryposis, multiple pterygium syndrome) have been linked to mutations. A homozygous mutation in CFL2, the gene for muscle cofilin, has been associated with nemaline myopathy in one family to date. Researchers have begun to decipher the mechanisms by which these mutations result in muscle weakness and contractures using a variety of in vitro assays to assess the effects of individual mutations on protein function and on sarcomere dynamics.
authors.affiliation: Institute for Neuromuscular Research, Children's Hospital at Westmead, Discipline of Pediatrics and Child Health, University of Sydney, Sydney, Australia. nigelc@chw.edu.au
authors.forename: Nigel F
authors.initials: NF
authors.lastname: Clarke
mesh_terms: D000818:Animals; D051340:Cofilin 2 / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D009135:Muscular Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009154:Mutation / Q000235:genetics; D014335:Tropomyosin / Q000235:genetics* / Q000378:metabolism; D014336:Troponin / Q000235:genetics* / Q000378:metabolism
chemical_list: D051340:Cofilin 2; D014335:Tropomyosin; D014336:Troponin