Mutations in the dystrophin gene are associated with sporadic dilated cardiomyopathy

Mol Genet Metab. Sep-Oct 2002;77(1-2):119-26. doi: 10.1016/s1096-7192(02)00153-1.


Dilated cardiomyopathy (DCM) is the major indication for heart transplantation. Approximately 30% of all DCM is thought to be inherited, while 70% is sporadic. Mutations in the dystrophin gene have been associated with the uncommon X-linked form of DCM. We hypothesized that missense mutations and other less severe mutations of the dystrophin gene might predispose to the common form of sporadic DCM. To test this hypothesis, 22kb of genomic dystrophin DNA was scanned with DOVAM-S in each of the 22 patients with sporadic DCM, including all 79 coding sequences and splice junctions, as well as six alternative exon 1 dystrophin isoforms (484kb, total). Three putative new mutations (IVS5+1 G>T, K18N, and F3228L) and seven polymorphisms were identified. The splice site mutation IVS5+1 is predicted to cause skipping of exon 5, which is within a region containing an actin binding site. The missense mutations occur at amino acids that display substantial evolutionary conservation. Screening of 236 control individuals failed to identify these three mutations. The three patients with putative mutations had CK-MM (creatine kinase, skeletal muscle) levels greater than 250 units while the 14 patients without mutations for which CK-MM were available had values ranging from 20 to 200. The first comprehensive mutation scanning of the exons and splice junctions of the dystrophin gene in patients with sporadic DCM presents the evidence that point mutations are associated with sporadic DCM without clinical evidence of skeletal myopathy. It may be prudent to measure CK-MM in all patients with dilated cardiomyopathy to identify candidates at high risk for dystrophin mutations.

Publication types

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

MeSH terms

  • Adolescent
  • Base Sequence
  • Cardiomyopathy, Dilated / genetics*
  • Child
  • Child, Preschool
  • Chromosomes, Human, X / genetics
  • Creatine Kinase / blood
  • Creatine Kinase, MM Form
  • DNA Mutational Analysis
  • Dystrophin / genetics*
  • Genetic Linkage
  • Genotype
  • Humans
  • Isoenzymes / blood
  • Male
  • Mosaicism
  • Muscular Dystrophy, Duchenne / genetics
  • Mutation*
  • Mutation, Missense
  • Phenotype
  • Polymorphism, Genetic


  • Dystrophin
  • Isoenzymes
  • Creatine Kinase
  • Creatine Kinase, MM Form