Abstract
We report the molecular findings in a child presenting with sideroblastic anemia and proximal tubulopathy. Analysis of mitochondrial DNA (mtDNA) from fibroblasts showed the presence of a 3.3-kb single deletion in 50% of the genomes. This mutation is, unlike other previously reported deletions in tubulopathy patients, not flanked by direct repeat sequences but by palindrome sequences at the deletion breakpoints, suggesting an unusual mechanism for production of deletion. These findings further expand our knowledge of the syndrome of anemia and tubulopathy due to single deletions of mtDNA.
This is a preview of subscription content, log in via an institution to check access.
References
DiMauro S, Bonilla E (1998) The molecular and genetic basis of neurological diseases. In: Rosenberg RN, Prusiner SB, DiMauro S, Barchi R (eds) Mitochondrial encephalomyopathies. Butterworth-Heinemann, Boston, pp 201–235
DiMauro S, Schon EA (2003) Mitochondrial respiratory-chain diseases. N Engl J Med 348:2656–2668
Wallace DC (1999) Mitochondrial diseases in man and mouse. Science 283:1482–1488
Rötig A, Cormier V, Blanche S, Bonnefont JP, Ledeist F, Romero N, Schmitz J, Rustin P, Fischer A, Saudubray JM (1990) Pearson′s marrow-pancreas syndrome. A multisystem disorder in infancy. J Clin Invest 86:1601–1608
Alter BP, Young NS (1998) Nathan and Oski′s hematology of infancy and childhood. In: Nathan DG, Orkin SH (eds) The bone marrow failure syndromes. Saunders, Philadelphia, pp 237–335
Morris AA, Lamont PJ, Clayton PT (1997) Pearson′s syndrome without marrow involvement. Arch Dis Child 77:56–57
Niaudet P, Rotig A (1996) Renal involvement in mitochondrial cytopathies. Pediatr Nephrol 10:368–373
Mita S, Rizzuto R, Moraes CT (1990) Recombination via flanking-repeats is a major cause of large scale-deletions of human mitochondrial DNA. Nucleic Acids Res 18:561–567
Shoffner JM, Lott MT, Voljavec AS, Soueidain SA, Costigan DA, Wallace DC (1989) Spontaneous Kearns-Sayre/chronic external ophthalmoplegia plus syndrome associated with a mitochondrial DNA deletion: a slip-replication model and metabolic therapy. Proc Natl Acad Sci U S A 86:7952–7956
Trinh TQ, Sinden RR (1993) The influence of primary and secondary DNA structure in deletion and duplication between direct repeats in Escherichia coli. Genetics 134:409–422
Saiwaki T, Shiga K, Fukuyama R, Tsutsumi Y, Fushiki S (2000) A unique junctional palindromic sequence in mitochondrial DNA from a patient with progressive external ophthalmoplegia. Mol Pathol 53:333–335
Acknowledgements
This study was supported by grants from the Diputación General de Aragón (P032–2000), Spanish Network for Mitochondrial Disorders (G03–011), and Spanish Ministerio de Ciencia y Tecnología (BCM2001–2421). A.S. was a recipient of a fellowship from the Mexican Government (CONACYT-121963).
Author information
Authors and Affiliations
Corresponding author
Additional information
A. Solano and G. Russo have contributed equally to the work
Rights and permissions
About this article
Cite this article
Solano, A., Russo, G., Playán, A. et al. De Toni-Debré-Fanconi syndrome due to a palindrome-flanked deletion in mitochondrial DNA. Pediatr Nephrol 19, 790–793 (2004). https://doi.org/10.1007/s00467-004-1473-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-004-1473-5