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.
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.
Authors: Xiomara Q Rosales; Julie M Gastier-Foster; Sarah Lewis; Malik Vinod; Devon L Thrush; Caroline Astbury; Robert Pyatt; Shalini Reshmi; Zarife Sahenk; Jerry R Mendell Journal: Muscle Nerve Date: 2010-07 Impact factor: 3.217
Authors: Eduard Gallardo; Noemi de Luna; Jordi Diaz-Manera; Ricardo Rojas-García; Lidia Gonzalez-Quereda; Bàrbara Flix; Antoine de Morrée; Silvère van der Maarel; Isabel Illa Journal: PLoS One Date: 2011-12-16 Impact factor: 3.240