A dysfunctional desmin mutation in a patient with severe generalized myopathy
Munoz-Marmol, Ana M.
Coulombe, Pierre A.
Mate, José L.
Fernández-Figueras, María Teresa
Navas-Palacios, José J.
Date of Issue1998
School of Biological Sciences
Mice lacking desmin produce muscle fibers with Z disks and normal sarcomeric organization. However, the muscles are mechanically fragile and degenerate upon repeated contractions. We report here a human patient with severe generalized myopathy and aberrant intrasarcoplasmic accumulation of desmin intermediate filaments. Muscle tissue from this patient lacks the wild-type desmin allele and has a desmin gene mutation encoding a 7-aa deletion within the coiled-coil segment of the protein. We show that recombinant desmin harboring this deletion cannot form proper desmin intermediate filament networks in cultured cells, nor is it able to assemble into 10-nm filaments in vitro. These findings provide direct evidence that a mutation in desmin can cause human myopathies.
National Academy of Sciences of the United States of America
© 1998 The National Academy of Sciences. This is the author created version of a work that has been peer reviewed and accepted for publication by Proceedings of the National Academy of Sciences of the United States of America, The National Academy of Sciences. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [DOI:http://dx.doi.org/10.1073/pnas.95.19.11312].