Infantile cardiomyopathy caused by a mutation in the overlapping region of mitochondrial ATPase 6 and 8 genes
- S M Ware1,2,
- N El-Hassan3,
- S G Kahler4,
- Q Zhang5,
- Y-W, Ma5,
- E Miller2,
- B Wong6,
- R L Spicer7,
- W J Craigen5,
- B A Kozel8,
- D K Grange8,
- L-J Wong5
- 1Division of Molecular Cardiovascular Biology, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
- 2Division of Human Genetics, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
- 3Department of Paediatrics, Division of Neonatology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
- 4Department of Paediatrics, Division of Medical Genetics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
- 5Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
- 6Division of Neurology, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
- 7Division of Paediatric Cardiology, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
- 8Division of Genetics and Genomic Medicine, Department of Paediatrics, Washington University School of Medicine, St. Louis, Missouri, USA
- 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
- 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
- Received 22 September 2008
- Revised 9 December 2008
- Accepted 31 December 2008
- Published Online First 2 February 2009
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.
Footnotes
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‣ A supplementary table is published online only at http://jmg.bmj.com/content/vol46/issue5
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For numbered affiliations see end of article
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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.
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Competing interests: None.
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Patient consent: Parental consent obtained.
