title: A mutation in the alpha tropomyosin gene TPM3 associated with autosomal dominant nemaline myopathy.
abstract: Nemaline myopathies are diseases characterized by the presence in muscle fibres of pathognomonic rod bodies. These are composed largely of alpha-actinin and actin. We have identified a missense mutation in the alpha-tropomyosin gene, TPM3, which segregates completely with the disease in a family whose autosomal dominant nemaline myopathy we had previously localized to chromosome 1p13-q25. The mutation substitutes an arginine residue for a highly conserved methionine in a putative actin-binding site near the N terminus of the alpha-tropomyosin. The mutation may strengthen tropomyosin - actin binding, leading to rod body formation, by adding a further basic residue to the postulated actin-binding motif.
authors.affiliation: Australian Neuromuscular Research Institute, Department of Pathology, University of Western Australia.
authors.forename: N G
authors.initials: NG
authors.lastname: Laing
authors.forename: S D
authors.initials: SD
authors.lastname: Wilton
authors.forename: P A
authors.initials: PA
authors.lastname: Akkari
authors.forename: S
authors.initials: S
authors.lastname: Dorosz
authors.forename: K
authors.initials: K
authors.lastname: Boundy
authors.forename: C
authors.initials: C
authors.lastname: Kneebone
authors.forename: P
authors.initials: P
authors.lastname: Blumbergs
authors.forename: S
authors.initials: S
authors.lastname: White
authors.forename: H
authors.initials: H
authors.lastname: Watkins
authors.forename: D R
authors.initials: DR
authors.lastname: Love
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002878:Chromosomes, Human, Pair 1; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D005091:Exons; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D017696:Myopathies, Nemaline / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D011110:Polymorphism, Genetic; D014335:Tropomyosin / Q000235:genetics*
chemical_list: D017931:DNA Primers; D014335:Tropomyosin; D004247:DNA