title: A missense mutation in the desmin rod domain is associated with autosomal dominant distal myopathy, and exerts a dominant negative effect on filament formation.
abstract: In some myopathies of distal onset, the intermediate filament desmin is abnormally accumulated in skeletal and cardiac muscle. We report the first point mutation in desmin cosegregating with an autosomal dominant form of desmin-related myopathy. The L345P desmin missense mutation occurs in a large, six generation Ashkenazi Jewish family. The mutation is located in an evolutionarily highly conserved position of the desmin coiled-coil rod domain important for dimer formation. L345P desmin is incapable of forming filamentous networks in transfected HeLa and SW13 cells. We conclude that the L345P desmin missense mutation causes myopathy by interfering in a dominant-negative manner with the dimerization-polymerization process of intermediate filament assembly.
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Sjöberg
authors.forename: C A
authors.initials: CA
authors.lastname: Saavedra-Matiz
authors.forename: D R
authors.initials: DR
authors.lastname: Rosen
authors.forename: E M
authors.initials: EM
authors.lastname: Wijsman
authors.forename: K
authors.initials: K
authors.lastname: Borg
authors.forename: S H
authors.initials: SH
authors.lastname: Horowitz
authors.forename: T
authors.initials: T
authors.lastname: Sejersen
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001706:Biopsy; D017931:DNA Primers; D003893:Desmin / Q000737:chemistry / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000473:pathology; D009136:Muscular Dystrophies / Q000235:genetics* / Q000473:pathology; D020125:Mutation, Missense; D010375:Pedigree
chemical_list: D017931:DNA Primers; D003893:Desmin