J. Marin-garcia et al., The complete sequence of mtDNA genes in idiopathic dilated cardiomyopathy shows novel missense and tRNA mutations, J CARD FAIL, 6(4), 2000, pp. 321-329
Background: Previous studies have shown that mitochondrial DNA (mtDNA) muta
tions are often present in patients with myocardial dysfunction. We sought
to assess the prevalence and significance of heart mtDNA sequence changes i
n patients with idiopathic dilated cardiomyopathy (DCM).
Methods and Results: DNA sequence of all the transfer ribonucleic acid (tRN
A), ribosomal RNA (rRNA), and structural genes in cardiac mtDNA of 28 patie
nts with DCM was determined acid compared with a control group that had no
evidence of heart disease. An increased number of point mutations were foun
d in DCM cardiac mtDNA when compared with controls. Both novel and previous
ly reported mutations were found in mitochondrial tRNA and structural genes
. One of these mutations was heteroplasmic and resulted in changing a highl
y conserved nucleotide in tRNA(Arg). Novel, heteroplasmic mtDNA mutations (
n = 4) specifying changes in moderate to highly conserved amino acid residu
es were found in COII, COIII, ND5, and cytb. These novel mtDNA mutations we
re found only in patients with severe reduction in mitochondrial enzyme act
ivities.
Conclusions: Our results indicate that a high incidence of mtDNA nucleotide
sequence changes in both tRNA and structural genes are present in DCM. Fiv
e heteroplasmic mutations were detected that both changed evolutionarily co
nserved residues (which may impair the function of proteins or tRNAs) and w
ere associated with specific enzymatic defects. These mutations could play
an important role in the pathogenesis of cardiomyopathy.