Abnormal expression of dysferlin in skeletal muscle and monocytes supports primary dysferlinopathy in patients with one mutated allele

Eur J Neurol. 2011 Jul;18(7):1021-3. doi: 10.1111/j.1468-1331.2010.03240.x. Epub 2010 Oct 18.


Background: In some cases, a definitive confirmation of dysferlinopathy cannot be achieved by DNA test, because the mutation is detected in one allele only.

Patients and methods: DYSFERLIN expression in skeletal muscle and peripheral blood monocytes (PBM) was studied by Western blot in two unrelated adult patients. The comparative C(T) method (ΔΔC(T) ) was used to calculate relative changes in dysferlin mRNA determined from real-time quantitative PCR experiments. The dysferlin gene was studied by direct sequencing of cDNA and genomic DNA and by Multiplex Ligation-dependent Probe Amplification (MLPA) analysis.

Results: A comparable severe reduction in dysferlin was demonstrated in both skeletal muscle and PBM. The expression of dysferlin mRNA was significantly reduced. A novel mutation in exon 47 (c.5289G>C) of the dysferlin gene in the heterozygous state, causing an amino acid change (p.Glu1763Asp), was detected in both patients. The MLPA analysis did not reveal any deletion or duplication.

Conclusions: Dysferlin and/or dysferlin mRNA abnormalities are diagnostic for dysferlinopathy when mutational analysis detects a mutation in one allele only. Analysis of dysferlin mRNA can be helpful for distinguishing symptomatic heterozygotes from such patients.

Publication types

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

MeSH terms

  • Adult
  • Alleles
  • Blotting, Western
  • DNA Mutational Analysis
  • Dysferlin
  • Female
  • Heterozygote
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Monocytes / metabolism
  • Monocytes / pathology*
  • Muscle Proteins / genetics*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology*
  • Muscular Dystrophies, Limb-Girdle / diagnosis*
  • Muscular Dystrophies, Limb-Girdle / genetics*
  • Pedigree
  • Point Mutation
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction


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

Supplementary concepts

  • Dysferlinopathy