A Mutation in the Dimerization Domain of Filamin C Causes a Novel Type of Autosomal Dominant Myofibrillar Myopathy
Copyright policy )A Mutation in the Dimerization Domain of Filamin C Causes a Novel Type of Autosomal Dominant Myofibrillar Myopathy
Myofibrillar myopathy (MFM) is a human disease that is characterized by focal myofibrillar destruction and pathological cytoplasmic protein aggregations. In an extended German pedigree with a novel form of MFM characterized by clinical features of a limb-girdle myopathy and morphological features of MFM, we identified a co-segregating, heterozygous nonsense mutation (8130G-->A; W2710X) in the filamin c gene (FLNC) on chromosome 7q32.1. The mutation is the first found in FLNC and is localized in the dimerization domain of filamin c. Functional studies showed that, in the truncated mutant protein, this domain has a disturbed secondary structure that leads to the inability to dimerize properly. As a consequence of this malfunction, the muscle fibers of our patients display massive cytoplasmic aggregates containing filamin c and several Z-disk-associated and sarcolemmal proteins.
- Ruhr University Bochum Germany
- University of Cologne Germany
- University of Bonn Germany
- CHILDREN'S HOSPITAL (NEW ORLEANS)
- Department of Neurology Netherlands
Genetic Markers, Cytoplasm, Heterozygote, Base Sequence, Models, Genetic, Biopsy, Filamins, Microfilament Proteins, Molecular Sequence Data, Immunohistochemistry, Contractile Proteins, Microscopy, Electron, Transmission, Muscular Diseases, Myofibrils, Codon, Nonsense, Mutation, Genetics, Humans, Genetics(clinical), Lod Score, Muscle, Skeletal, Dimerization, Institut für Biochemie und Biologie
Genetic Markers, Cytoplasm, Heterozygote, Base Sequence, Models, Genetic, Biopsy, Filamins, Microfilament Proteins, Molecular Sequence Data, Immunohistochemistry, Contractile Proteins, Microscopy, Electron, Transmission, Muscular Diseases, Myofibrils, Codon, Nonsense, Mutation, Genetics, Humans, Genetics(clinical), Lod Score, Muscle, Skeletal, Dimerization, Institut für Biochemie und Biologie
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