Dysferlin-deficient muscular dystrophy features amyloidosis

Ann Neurol. 2008 Mar;63(3):323-8. doi: 10.1002/ana.21309.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amino Acid Sequence
  • Amino Acid Substitution / genetics
  • Amyloidosis / diagnosis
  • Amyloidosis / genetics*
  • Amyloidosis / metabolism*
  • Dysferlin
  • Female
  • Humans
  • Male
  • Membrane Proteins / deficiency*
  • Membrane Proteins / genetics*
  • Middle Aged
  • Molecular Sequence Data
  • Muscle Proteins / deficiency*
  • Muscle Proteins / genetics*
  • Muscular Dystrophies, Limb-Girdle / diagnosis
  • Muscular Dystrophies, Limb-Girdle / genetics*
  • Muscular Dystrophies, Limb-Girdle / metabolism*
  • Protein Structure, Tertiary / genetics


  • DYSF protein, human
  • Dysferlin
  • Membrane Proteins
  • Muscle Proteins