X-linked dilated cardiomyopathy. Novel mutation of the dystrophin gene

Ann N Y Acad Sci. 1995 Mar 27;752:470-91. doi: 10.1111/j.1749-6632.1995.tb17457.x.


We report on a family with a severe form of X-linked dilated cardiomyopathy (DCM). Two brothers, the elder requiring heart transplantation, and a maternal cousin presented elevated creatine kinase levels, increased right ventricular diameters and electrocardiographic abnormalities. All complained of exertional cramping myalgia, but none had muscle weakness or a pathological electromyogram. Muscle biopsies of these individuals revealed a mild myopathic picture with atrophic type I and hypertrophic type II fibers. Immunofluorescence using N- and C-terminal antibodies (dys-2, dys-3) against the dystrophin protein showed preserved, but reduced intensity of staining of the sarcolemmal membranes. Using the same two antibodies, Western blot analyses revealed a dystrophin molecule of the expected molecular weight, which was quantitatively reduced by 80%. However, the dys-1 antibody, directed against the mid rod region of the dystrophin protein, did not react with dystrophin both on Western blot and immunofluorescence. Linkage analysis with polymorphic markers of the dystrophin gene revealed an identical haplotype at the 5' region in all affected individuals (two point lod score of 1.93, phi = 0). A deletion of exons 48, 45-53, 2-7 and 1 including the promoter region of the dystrophin gene, as described in rare cases with similar clinical signs could be excluded by multiplex PCR and Southern blot analyses of this DCM family. In addition, a major splice-mutation of dystrophin mRNA was excluded by RT-PCR of skeletal and heart muscle tissue. Therefore, we conclude that a novel mutation in the 5' region of the dystrophin gene phenotypically leads to this severe form of DCM. Extensive analyses of the dystrophin gene, in particular of the sequences coding for the antigenic determinants of the dys-1 antibody in the mid rod region, may identify the molecular cause of this monogenetic form of DCM.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Alternative Splicing
  • Biopsy
  • Cardiomyopathy, Dilated / genetics*
  • Cardiomyopathy, Dilated / metabolism
  • Cardiomyopathy, Dilated / pathology
  • Chromosome Mapping
  • DNA Primers
  • Dystrophin / analysis
  • Dystrophin / biosynthesis
  • Dystrophin / genetics*
  • Exons
  • Female
  • Genetic Linkage
  • Genetic Markers
  • Humans
  • Lod Score
  • Male
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Myosins / analysis
  • Myosins / biosynthesis
  • Pedigree
  • Polymerase Chain Reaction
  • RNA, Messenger / biosynthesis
  • Recombination, Genetic
  • Sequence Deletion*
  • X Chromosome*


  • DNA Primers
  • Dystrophin
  • Genetic Markers
  • RNA, Messenger
  • Myosins