title: Dysferlin-deficient muscular dystrophy features amyloidosis.
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.
  
  
  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.
authors.affiliation: Muscle Research Unit, Experimental and Clinical Research Center at the Charité and the Max-Delbrück Center, Berlin, Germany. simone.spuler@charite.de
authors.forename: Simone
authors.initials: S
authors.lastname: Spuler
authors.forename: Miriam
authors.initials: M
authors.lastname: Carl
authors.forename: Joanna
authors.initials: J
authors.lastname: Zabojszcza
authors.forename: Volker
authors.initials: V
authors.lastname: Straub
authors.forename: Kate
authors.initials: K
authors.lastname: Bushby
authors.forename: Steven A
authors.initials: SA
authors.lastname: Moore
authors.forename: Sylvia
authors.initials: S
authors.lastname: Bähring
authors.forename: Katrin
authors.initials: K
authors.lastname: Wenzel
authors.forename: Uwe
authors.initials: U
authors.lastname: Vinkemeier
authors.forename: Christoph
authors.initials: C
authors.lastname: Rocken
mesh_terms: 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
chemical_list: C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins