TY - JOUR
T1 - A dysfunctional desmin mutation in a patient with severe generalized myopathy
AU - Muñoz-Mármol, Ana M.
AU - Strasser, Geraldine
AU - Isamat, Marcos
AU - Coulombe, Pierre A.
AU - Yang, Yanmin
AU - Roca, Xavier
AU - Vela, Elena
AU - Mate, José L.
AU - Coll, Jaume
AU - Fernández-Figueras, María Teresa
AU - Navas-Palacios, José J.
AU - Ariza, Aurelio
AU - Fuchs, Elaine
PY - 1998/9/15
Y1 - 1998/9/15
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.95.19.11312
DO - 10.1073/pnas.95.19.11312
M3 - Article
C2 - 9736733
AN - SCOPUS:0038669889
SN - 0027-8424
VL - 95
SP - 11312
EP - 11317
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 19
ER -