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Am J Hum Genet. 2005 Aug;77(2):297-304. Epub 2005 May 31.

A mutation in the dimerization domain of filamin c causes a novel type of autosomal dominant myofibrillar myopathy.

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1
Department of Neurology, Neuromuscular Center Ruhrgebiet, Ruhr-University Bochum, Bochum, Germany.

Abstract

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.

PMID:
15929027
PMCID:
PMC1224531
DOI:
10.1086/431959
[Indexed for MEDLINE]
Free PMC Article
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