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Infantile cardiomyopathy caused by a mutation in the overlapping region of mitochondrial ATPase 6 and 8 genes
  1. S M Ware1,2,
  2. N El-Hassan3,
  3. S G Kahler4,
  4. Q Zhang5,
  5. Y-W, Ma5,
  6. E Miller2,
  7. B Wong6,
  8. R L Spicer7,
  9. W J Craigen5,
  10. B A Kozel8,
  11. D K Grange8,
  12. L-J Wong5
  1. 1
    Division of Molecular Cardiovascular Biology, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
  2. 2
    Division of Human Genetics, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
  3. 3
    Department of Paediatrics, Division of Neonatology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
  4. 4
    Department of Paediatrics, Division of Medical Genetics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
  5. 5
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
  6. 6
    Division of Neurology, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
  7. 7
    Division of Paediatric Cardiology, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
  8. 8
    Division of Genetics and Genomic Medicine, Department of Paediatrics, Washington University School of Medicine, St. Louis, Missouri, USA
  1. For clinical information Dr S M Ware, Cincinnati Children’s Hospital Medical Center, 240 Albert Sabin Way, MLC 7020, Cincinnati, Ohio 45229, USA; stephanie.ware{at}cchmc.orgBaylor College of Medicine, Dept of Molecular and Human Genetics, One Baylor Plaza, Houston, Texas 77030, USA; ljwong{at}bcm.edu
  2. For biochemical information Dr L-J Wong, Cincinnati Children’s Hospital Medical Center, 240 Albert Sabin Way, MLC 7020, Cincinnati, Ohio 45229, USA; stephanie.ware{at}cchmc.orgBaylor College of Medicine, Dept of Molecular and Human Genetics, One Baylor Plaza, Houston, Texas 77030, USA; ljwong{at}bcm.edu

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.

https://doi.org/10.1136/jmg.2008.063149

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    Footnotes

    • ▸ A supplementary table is published online only at http://jmg.bmj.com/content/vol46/issue5

    • For numbered affiliations see end of article

    • Funding: This study was supported by grants from the Children’s Cardiomyopathy Foundation to SMW and a National Institutes of Health award (5R01 CA100023) to LJW.

    • Competing interests: None.

    • Patient consent: Parental consent obtained.