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Infantile cardiomyopathy caused by the T14709C mutation in the mitochondrial tRNA glutamic acid gene

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Abstract

A 6-week-old child presented with hypotonia, myopathy, and a rapidly worsening dilated cardiomyopathy with severe atrial and ventricular arrhythmias and pulmonary hypertension, which proved fatal at age 3 months. Biochemical analysis showed a combined deficiency of the enzymatic activities of complexes I and IV and molecular studies identified a T14709C mutation in the mitochondrial tRNA glutamic acid gene. A review of symptomatology in patients with this mutation shows that it mainly presents in childhood or young adults with mild myopathy and diabetes mellitus. Infants with a high, nearly homoplasmic mutant load can present with more severe symptoms including cardiomyopathy. Families with this mitochondrial DNA mutation should be aware that increased mutant load in a subsequent generation may result in severe and often fatal cardiac symptoms.

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Abbreviations

mtDNA:

mitochondrial DNA

tRNA:

transfer RNA

COX:

cytochrome c oxidase

ATP:

adenosine triphosphate

ADP:

adenosine diphosphate

RFLP:

restriction fragment length polymorphism

PCR:

polymerase chain reaction

PAGE:

polyacrylamide gel electrophoresis

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Acknowledgments

The authors would like to thank Dr. Eric Shoubridge, Montreal Neurological Institute, Montreal, Canada, for performing the blue native polyacrylamide gel electrophoresis experiments.

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Authors and Affiliations

  1. The Department of Pediatrics, The University of Colorado at Denver Health Sciences Center and The Children’s Hospital, Denver, CO, USA

    Johan L. K. Van Hove, Cynthia Freehauf, Shelley Miyamoto & Janet A. Thomas

  2. Department of Pediatrics, The State University of New York at Buffalo, Buffalo, NY, USA

    Georgirene D. Vladutiu

  3. Department of Neurology, Columbia College of Physicians and Surgeons, New York, NY, USA

    Jacklyn Pancrudo, Eduardo Bonilla & Sara Shanske

  4. The Department of Pathology, The University of Colorado at Denver Health Sciences Center and The Children’s Hospital, Denver, CO, USA

    Mark A. Lovell & Gary W. Mierau

  5. Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado Health Sciences Center at Fitzsimmons, Mail stop 8313, RC-1 North, 12800 E. 19th Avenue, Room P18-4132, PO Box 6511, Aurora, CO, 80045, USA

    Johan L. K. Van Hove

Authors
  1. Johan L. K. Van Hove
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  2. Cynthia Freehauf
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  3. Shelley Miyamoto
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  4. Georgirene D. Vladutiu
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  5. Jacklyn Pancrudo
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  6. Eduardo Bonilla
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  7. Mark A. Lovell
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  8. Gary W. Mierau
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  9. Janet A. Thomas
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  10. Sara Shanske
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Correspondence to Johan L. K. Van Hove.

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Van Hove, J.L.K., Freehauf, C., Miyamoto, S. et al. Infantile cardiomyopathy caused by the T14709C mutation in the mitochondrial tRNA glutamic acid gene. Eur J Pediatr 167, 771–776 (2008). https://doi.org/10.1007/s00431-007-0587-8

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  • DOI: https://doi.org/10.1007/s00431-007-0587-8

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