Dysferlin-deficient muscular dystrophy features amyloidosis.
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.


CONCLUSIONS
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.
Spuler
Simone
S
Muscle Research Unit, Experimental and Clinical Research Center at the Charité and the Max-Delbrück Center, Berlin, Germany. simone.spuler@charite.de
Carl
Miriam
M
Zabojszcza
Joanna
J
Straub
Volker
V
Bushby
Kate
K
Moore
Steven A
SA
Bähring
Sylvia
S
Wenzel
Katrin
K
Vinkemeier
Uwe
U
Rocken
Christoph
C
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000686:Amyloidosis / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D000073939:Dysferlin; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000172:deficiency* / Q000235:genetics*; D049288:Muscular Dystrophies, Limb-Girdle / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000235:genetics
C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins