ORIGINAL ARTICLES

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

S M Ware^1,2, 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

¹ Division of Molecular Cardiovascular Biology, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
² Division of Human Genetics, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
³ Department of Paediatrics, Division of Neonatology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
⁴ Department of Paediatrics, Division of Medical Genetics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
⁵ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA
⁶ Division of Neurology, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
⁷ Division of Paediatric Cardiology, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
⁸ Division 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

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.8528TC 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.

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