The complete sequence of mtDNA genes in idiopathic dilated cardiomyopathy shows novel missense and tRNA mutations

Jose Marin-Garcia, Michael J. Goldenthal, Radha Ananthakrishnan, Mary Ella Pierpont

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


Background: Previous studies have shown that mitochondrial DNA (mtDNA) mutations are often present in patients with myocardial dysfunction. We sought to assess the prevalence and significance of heart mtDNA sequence changes in patients with idiopathic dilated cardiomyopathy (DCM). Methods and Results: DNA sequence of all the transfer ribonucleic acid (tRNA), ribosomal RNA (rRNA), and structural genes in cardiac mtDNA of 28 patients with DCM was determined and compared with a control group that had no evidence of heart disease. An increased number of point mutations were found in DCM cardiac mtDNA when compared with controls. Both novel and previously reported mutations were found in mitochondrial tRNA and structural genes. One of these mutations was heteroplasmic and resulted in changing a highly conserved nucleotide in tRNAArg. Novel, heteroplasmic mtDNA mutations (n = 4) specifying changes in moderate to highly conserved amino acid residues were found in COII, COIII, ND5, and cytb. These novel mtDNA mutations were found only in patients with severe reduction in mitochondrial enzyme activities. Conclusions: Our results indicate that a high incidence of mtDNA nucleotide sequence changes in both tRNA and structural genes are present in DCM. Five heteroplasmic mutations were detected that both changed evolutionarily conserved residues (which may impair the function of proteins or tRNAs) and were associated with specific enzymatic defects. These mutations could play an important role in the pathogenesis of cardiomyopathy.

Original languageEnglish (US)
Pages (from-to)321-329
Number of pages9
JournalJournal of cardiac failure
Issue number4
StatePublished - Dec 2000
Externally publishedYes

Bibliographical note

Funding Information:
repeatedly confirmed from independentPCR reactions and are unlikely to represent sequencing or polymerase errors. The assessment of heteroplasmy (mixed population of mutant and wild-type alleles) of any given mutation (23) was made by densitometric analysis (using NIH Image 1.33 software; National Institutes of Health, Bethesda, MD) from the sequencing profiles obtained from the LICOR automatic sequencer and Base ImageIR software (LICOR). The extent of heteroplasmy of the mutant alleles described in this study ranged from 65% to 90% relative to the wild-type allele.


  • Dilated cardiomyopathy
  • Mitochondria
  • Oxidative phosphorylation


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