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Dysferlin-deficient muscular dystrophy features amyloidosis

Item Type:Article
Title:Dysferlin-deficient muscular dystrophy features amyloidosis
Creators Name:Spuler, S. and Carl, M. and Zabojszcza, J. and Straub, V. and Bushby, K. and Moore, S.A. and Baehring, S. and Wenzel, K. and Vinkemeier, U. and Rocken, C.
Abstract:OBJECTIVE: Dysferlin (DYSF) gene mutations cause limb girdle muscular dystrophy type 2B and Miyoshi's myopathy. The consequences of DYSF mutations on protein structure are poorly understood. METHODS: The gene encoding dysferlin was sequenced in patients with suspected dysferlin-deficient muscular dystrophy. Muscle biopsy specimens were analyzed by histochemistry, immunohistochemistry, and electron microscopy. Antibodies against N-terminal dysferlin-peptides were raised. RESULTS: We found three families with muscular dystrophy caused by homozygous or compound heterozygous DYSF mutations featuring sarcolemmal and interstitial amyloid deposits. These mutations were all located in the N-terminal region of the protein. Dysferlin was a constituent of the amyloid deposits. INTERPRETATION: Limb girdle muscular dystrophy type 2B is the first muscular dystrophy associated with amyloidosis. Molecular treatment strategies will necessarily have to consider the presence of amyloidogenesis.
Keywords:Amino Acid Sequence, Amino Acid Substitution, Amyloidosis, Limb-Girdle Muscular Dystrophies, Membrane Proteins, Molecular Sequence Data, Muscle Proteins, Tertiary Protein Structure
Source:Annals of Neurology
Page Range:323-328
Date:March 2008
Official Publication:https://doi.org/10.1002/ana.21309
PubMed:View item in PubMed

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