title: Tropomyosins in skeletal muscle diseases.
abstract: A number of congenital muscle diseases and disorders are caused by mutations in genes that encode the proteins present in or associated with the thin filaments of the muscle sarcomere. These genes include alpha-skeletal actin (ACTA1), beta-tropomyosin (TPM2), alpha-tropomyosin slow (TPM3), nebulin (NEB), troponin I fast (TNNI2), troponin T slow (TNNT1), troponin T fast (TNNT3) and cofilin (CFL2). Mutations in two of the four tropomyosin (Tm) genes, TPM2 and TPM3, result in at least three different skeletal muscle diseases and one disorder as distinguished by the presence of specific clinical features and/or structural abnormalities--nemaline myopathy (TPM2 and TPM3), distal arthrogryposis (TPM2), cap disease (TPM2) and congenital fiber type disproportion (TPM3). These diseases have overlapping clinical features and pathologies and there are cases of family members who have the same mutation, but different diseases (Table 1). The relatively recent discovery of nonmuscle or cytoskeletal Tms in skeletal muscle adds to this complexity since it is now possible that a disease-causing mutation could be in a striated isoform and a cytoskeletal isoform both present in muscle.
authors.affiliation: Muscle Development Unit, Children's Medical Resaerch Institute, University of Sydney, Sydney, Australia.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Kee
authors.forename: Edna C
authors.initials: EC
authors.lastname: Hardeman
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D003599:Cytoskeleton / Q000378:metabolism; D005838:Genotype; D006801:Humans; D051379:Mice; D008954:Models, Biological; D008957:Models, Genetic; D018482:Muscle, Skeletal / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism; D009135:Muscular Diseases / Q000378:metabolism*; D009154:Mutation; D020033:Protein Isoforms; D012518:Sarcomeres / Q000378:metabolism; D014335:Tropomyosin / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*
chemical_list: D000199:Actins; D020033:Protein Isoforms; D014335:Tropomyosin