Miyoshi myopathy patients with novel 5' splicing donor site mutations showed different dysferlin immunostaining at the sarcolemma

Acta Neuropathol. 2002 Dec;104(6):615-20. doi: 10.1007/s00401-002-0593-x. Epub 2002 Jul 19.


We analyzed five clinically defined cases of Miyoshi myopathy both genetically and immunologically. Western blot of muscle specimens confirmed that all of these patients had dysferlin deficiency. Immunohistochemistry revealed that two of the five patients showed positive dysferlin immunostaining. Subsequent mutation analysis of the dysferlin gene in these two patients revealed that both had novel 5' splicing donor site mutations. One patient with a homozygous G to C substitution at nucleotide 1036+1 exon 6 splicing donor site showed patchy sarcolemmal dysferlin immunostaining. The second patient with both a heterozygous G to A substitution at nucleotide 1310+1 exon 10 splicing donor site and a heterozygous C to G substitution at nucleotide 1939 (which induces Tyr 522 Stop of exon 18) showed both patchy sarcolemmal and diffuse cytoplasmic dysferlin immunostaining. In contrast to Becker muscular dystrophy, the clinical course and severity of dysferlin staining positive patients was not clearly different from negative patients. These results suggest that a splicing mutation of the dysferlin gene may have the potential to cause decreased dysferlin expression but may not be related to the milder clinical phenotype.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Dysferlin
  • Female
  • Humans
  • Male
  • Membrane Proteins*
  • Middle Aged
  • Muscle Proteins / analysis*
  • Muscle Proteins / genetics*
  • Muscle Proteins / immunology
  • Muscular Diseases / genetics*
  • Muscular Diseases / immunology*
  • Muscular Diseases / pathology
  • Mutation / genetics*
  • Phenotype*
  • RNA Splice Sites / genetics*
  • Sarcolemma / genetics*
  • Sarcolemma / immunology*
  • Sarcolemma / pathology
  • Severity of Illness Index


  • DYSF protein, human
  • Dysferlin
  • Membrane Proteins
  • Muscle Proteins
  • RNA Splice Sites