Mitochondrial tRNAPhe mutation as a cause of end-stage renal disease in childhood (original) (raw)

Abstract

Background

We identified a mitochondrial tRNA mutation (m.586 G > A) in a patient with renal failure and symptoms consistent with a mitochondrial cytopathy. This mutation was of unclear significance due to the absence of consistent reports of linkage to specific disease phenotypes and any data pertaining to its effects on mitochondrial function.

Case-Diagnosis/Treatment

A 16-month-old girl with failure-to-thrive, developmental regression, persistent lactic acidosis, hypotonia, gastrointestinal dysmotility, adrenal insufficiency, and hematologic abnormalities developed hypertension and renal impairment with chronic tubulointerstitial fibrosis, progressing to renal failure with the need for peritoneal dialysis. Evaluation of her muscle and blood led to the identification of a mutation of the mitochondrial tRNA for phenylalanine, m.586 G > A.

Conclusions

The m.586 G > A mutation is pathogenic and a cause of end-stage renal disease in childhood. The mutation interferes with the stability of tRNAPhe and affects the translation of mitochondrial proteins and the stability of the electron transport chain.

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Fig. 1

Abbreviations

mtDNA:

Mitochondrial DNA

MTTF:

Mitochondrial tRNAPhe

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Acknowledgments

This work was supported by NIH grant HD58022 to NS. The authors thank Michael King for the gift of the 143B ρ0 cell line and guidance on making cybrids, Marni Falk for her participation in the care of our patient, and the family that participated in this research study.

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Authors and Affiliations

  1. Division of Genetics, Department of Pediatrics, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave, Box 777, Rochester, NY, 14623, USA
    Kristin E. D’Aco
  2. Section of Biochemical Genetics, The Children’s Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA, 19104, USA
    Megan Manno, Colleen Clarke, Jaya Ganesh & Neal Sondheimer
  3. Division of Nephrology, The Children’s Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA, 19104, USA
    Kevin E. C. Meyers
  4. Department of Pediatrics, The University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA
    Jaya Ganesh, Kevin E. C. Meyers & Neal Sondheimer

Authors

  1. Kristin E. D’Aco
  2. Megan Manno
  3. Colleen Clarke
  4. Jaya Ganesh
  5. Kevin E. C. Meyers
  6. Neal Sondheimer

Corresponding author

Correspondence toNeal Sondheimer.

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D’Aco, K.E., Manno, M., Clarke, C. et al. Mitochondrial tRNAPhe mutation as a cause of end-stage renal disease in childhood.Pediatr Nephrol 28, 515–519 (2013). https://doi.org/10.1007/s00467-012-2354-y

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