Symptomatic dysferlin gene mutation carriers: characterization of two cases

Neurology. 2007 Apr 17;68(16):1284-9. doi: 10.1212/01.wnl.0000256768.79353.60. Epub 2007 Feb 7.


Objective: To describe two symptomatic dysferlin gene mutation carriers.

Methods: One patient had limb girdle weakness. His brother was diagnosed with limb girdle muscular dystrophy 2B with two mutations in the dysferlin gene (D625Y and E1734G). The second patient had distal weakness. He had two sons with Miyoshi myopathy with a homozygous mutation (G519R). We performed immunofluorescence (dystrophin, DAG proteins, dysferlin, caveolin-3), Western blot (dysferlin, caveolin-3, calpain-3), and real-time PCR (dysferlin) using skeletal muscle samples. We also studied dysferlin in peripheral blood monocytes (PBMs) by Western blot.

Results: In addition to the muscle weakness, both patients showed elevated creatine kinase and abnormal muscle MRI. They presented a mutation in only one allele after screening of the whole gene (skeletal muscle and monocyte mRNA and genomic DNA). A muscle biopsy specimen showed moderate dystrophic changes and patchy dysferlin expression in the sarcolemma. Western blot of both PBMs and skeletal muscle demonstrated a significant reduction in dysferlin. All the other proteins including caveolin-3 and calpain-3 were normal. Real-time PCR showed normal levels of dysferlin mRNA vs the patients' affected relatives.

Conclusions: The diagnosis of symptomatic carriers of dysferlin mutations should be considered when a pathologic pattern of dysferlin protein is observed.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Creatine Kinase / metabolism
  • DNA Mutational Analysis
  • Dysferlin
  • Female
  • Genetic Carrier Screening / methods
  • Genetic Markers
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing
  • Heterozygote
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics*
  • Middle Aged
  • Muscle Proteins / deficiency
  • Muscle Proteins / genetics*
  • Muscle Proteins / metabolism
  • Muscle Weakness / diagnosis
  • Muscle Weakness / genetics*
  • Muscle Weakness / physiopathology*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Muscular Diseases / diagnosis
  • Muscular Diseases / genetics*
  • Muscular Diseases / physiopathology*
  • Mutation / genetics
  • Pedigree


  • DYSF protein, human
  • Dysferlin
  • Genetic Markers
  • Membrane Proteins
  • Muscle Proteins
  • Creatine Kinase