Infantile cardiomyopathy caused by a mutation in the overlapping region of mitochondrial ATPase 6 and 8 genes

Background: Infantile cardiomyopathy is a genetically heterogeneous disorder with significant morbidity and mortality.

Methods: This study aimed to identify the mutation present in four unrelated patients who presented as infants with isolated hypertrophic cardiomyopathy.

Results: In all four, a novel mitochondrial m.8528T-->C mutation was identified. This results in a change of the initiation codon in ATPase 6 to threonine and a concurrent change from a highly conserved hydrophobic amino acid, tryptophan, at position 55 of ATPase 8 to a highly basic arginine. To our knowledge, this is the first report of a mutation affecting both mitochondrial genome-encoded complex V subunit proteins. Testing of the relatives of one patient indicated that the mutation is heteroplasmic and correlated with disease.

Conclusion: Mitochondrial genome sequencing should be considered in patients with infantile hypertrophic cardiomyopathy.