Journal Article

A Missense Mutation in the Desmin Rod Domain Is Associated with Autosomal Dominant Distal Myopathy, and Exerts a Dominant Negative Effect on Filament Formation

Gunnar Sjöberg, Carlos A. Saavedra-Matiz, Daniel R. Rosen, Ellen M. Wijsman, Kristian Borg, Steven H. Horowitz and Thomas Sejersen

in Human Molecular Genetics

Volume 8, issue 12, pages 2191-2198
Published in print November 1999 | ISSN: 0964-6906
Published online November 1999 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/8.12.2191
A Missense Mutation in the Desmin Rod Domain Is Associated with Autosomal Dominant Distal Myopathy, and Exerts a Dominant Negative Effect on Filament Formation

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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.

Journal Article.  5182 words.  Illustrated.

Subjects: Genetics and Genomics

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