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

J Med Genet. 2009 May;46(5):308-14. doi: 10.1136/jmg.2008.063149. Epub 2009 Feb 2.

Abstract

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.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cardiomyopathy, Hypertrophic / enzymology
  • Cardiomyopathy, Hypertrophic / genetics*
  • Cardiomyopathy, Hypertrophic / pathology
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mitochondrial Proton-Translocating ATPases / genetics*
  • Mutation*

Substances

  • ATP synthase subunit 6
  • MT-ATP8 protein, human
  • Mitochondrial Proton-Translocating ATPases