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. 1994 Nov;71(5):419–422. doi: 10.1136/adc.71.5.419

Mitochondrial DNA 8993 (NARP) mutation presenting with a heterogeneous phenotype including 'cerebral palsy'.

A Fryer 1, R Appleton 1, M G Sweeney 1, L Rosenbloom 1, A E Harding 1
PMCID: PMC1030055  PMID: 7529982

Abstract

The mitochondrial DNA (mtDNA) mutation 8993 is an important cause of Leigh's encephalopathy. A family is reported where other affected members have presented with non-specific delayed development or cerebral palsy. The diagnosis should be considered not only in children with Leigh's encephalopathy, but also in those with mild neurological dysfunction (including cerebral palsy) if there is a pigmentary retinopathy or a family history of neurological or ophthalmological disease. There was some correlation in this family between the disease severity and the proportion of mutant mtDNA in the blood. This mutation appears to segregate to high levels of mutant mtDNA rapidly within pedigrees and the mother of a severely affected child has a high risk of having further children with a high proportion of mutant mtDNA and a severe phenotype.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ciafaloni E., Santorelli F. M., Shanske S., Deonna T., Roulet E., Janzer C., Pescia G., DiMauro S. Maternally inherited Leigh syndrome. J Pediatr. 1993 Mar;122(3):419–422. doi: 10.1016/s0022-3476(05)83431-6. [DOI] [PubMed] [Google Scholar]
  2. Harding A. E., Holt I. J., Sweeney M. G., Brockington M., Davis M. B. Prenatal diagnosis of mitochondrial DNA8993 T----G disease. Am J Hum Genet. 1992 Mar;50(3):629–633. [PMC free article] [PubMed] [Google Scholar]
  3. Holt I. J., Harding A. E., Petty R. K., Morgan-Hughes J. A. A new mitochondrial disease associated with mitochondrial DNA heteroplasmy. Am J Hum Genet. 1990 Mar;46(3):428–433. [PMC free article] [PubMed] [Google Scholar]
  4. Sakuta R., Goto Y., Horai S., Ogino T., Yoshinaga H., Ohtahara S., Nonaka I. Mitochondrial DNA mutation and Leigh's syndrome. Ann Neurol. 1992 Oct;32(4):597–598. doi: 10.1002/ana.410320428. [DOI] [PubMed] [Google Scholar]
  5. Santorelli F. M., Shanske S., Macaya A., DeVivo D. C., DiMauro S. The mutation at nt 8993 of mitochondrial DNA is a common cause of Leigh's syndrome. Ann Neurol. 1993 Dec;34(6):827–834. doi: 10.1002/ana.410340612. [DOI] [PubMed] [Google Scholar]
  6. Shoffner J. M., Fernhoff P. M., Krawiecki N. S., Caplan D. B., Holt P. J., Koontz D. A., Takei Y., Newman N. J., Ortiz R. G., Polak M. Subacute necrotizing encephalopathy: oxidative phosphorylation defects and the ATPase 6 point mutation. Neurology. 1992 Nov;42(11):2168–2174. doi: 10.1212/wnl.42.11.2168. [DOI] [PubMed] [Google Scholar]
  7. Smith K. H., Johns D. R., Heher K. L., Miller N. R. Heteroplasmy in Leber's hereditary optic neuropathy. Arch Ophthalmol. 1993 Nov;111(11):1486–1490. doi: 10.1001/archopht.1993.01090110052022. [DOI] [PubMed] [Google Scholar]
  8. Tatuch Y., Christodoulou J., Feigenbaum A., Clarke J. T., Wherret J., Smith C., Rudd N., Petrova-Benedict R., Robinson B. H. Heteroplasmic mtDNA mutation (T----G) at 8993 can cause Leigh disease when the percentage of abnormal mtDNA is high. Am J Hum Genet. 1992 Apr;50(4):852–858. [PMC free article] [PubMed] [Google Scholar]
  9. Tatuch Y., Pagon R. A., Vlcek B., Roberts R., Korson M., Robinson B. H. The 8993 mtDNA mutation: heteroplasmy and clinical presentation in three families. Eur J Hum Genet. 1994;2(1):35–43. doi: 10.1159/000472339. [DOI] [PubMed] [Google Scholar]
  10. de Vries D. D., van Engelen B. G., Gabreëls F. J., Ruitenbeek W., van Oost B. A. A second missense mutation in the mitochondrial ATPase 6 gene in Leigh's syndrome. Ann Neurol. 1993 Sep;34(3):410–412. doi: 10.1002/ana.410340319. [DOI] [PubMed] [Google Scholar]

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