Sporadic intragenic inversion of the mitochondrial DNA MTND1 gene causing fatal infantile lactic acidosis

Emma L. Blakely, Katherine J. Rennie, Linda Jones, Mattias Elstner, Zofia M.A. Chrzanowska-Lightowlers, Christopher Bradford White, Julian P.H. Shield, Daniela T. Pilz, Douglass M. Turnbull, Joanna Poulton, Robert W. Taylor

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Mutations of mitochondrial DNA (mtDNA) are an important cause of genetic disease, yet rarely present in the neonatal period. Here we report the clinical, biochemical, and molecular genetic findings of an infant who died at the age of 1 mo with marked biventricular hypertrophy, aortic coarctation, and severe lactic acidosis due to a previously described but unusual mtDNA mutation, a 7-bp intragenic inversion within the mitochondrial gene encoding ND1 protein of complex I (MTND1). In direct contrast to the previous case, an adult with exercise intolerance who only harbored the mutation in muscle, the MTND1 inversion in our patient was present at high levels in several tissues including the heart, muscle, liver, and cultured skin fibroblasts. There was no evidence of the mutation or respiratory complex I defect in a muscle biopsy from the patient's mother. Transmitochondrial cytoplasmic hybrids (cybrids) containing high mutant loads of the inversion expressed the biochemical defect but apparently normal levels of the assembled complex. Our report highlights the enormous phenotypic diversity that exists among pathogenic mtDNA mutations and reemphasizes the need for appropriate genetic counseling for families affected by mtDNA disease.

Original languageEnglish (US)
Pages (from-to)440-444
Number of pages5
JournalPediatric Research
Volume59
Issue number3
DOIs
StatePublished - Mar 1 2006

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Mitochondrial DNA
Mutation
Genes
Molecular Biology
Electron Transport Complex I
Mitochondrial Diseases
Muscles
Lactic Acidosis
Inborn Genetic Diseases
Aortic Coarctation
Mitochondrial Genes
Genetic Counseling
Hypertrophy
Myocardium
Fibroblasts
Mothers
Fatal Infantile Lactic Acidosis
Exercise
Biopsy
Skin

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Blakely, E. L., Rennie, K. J., Jones, L., Elstner, M., Chrzanowska-Lightowlers, Z. M. A., White, C. B., ... Taylor, R. W. (2006). Sporadic intragenic inversion of the mitochondrial DNA MTND1 gene causing fatal infantile lactic acidosis. Pediatric Research, 59(3), 440-444. https://doi.org/10.1203/01.pdr.0000198771.78290.c4

Sporadic intragenic inversion of the mitochondrial DNA MTND1 gene causing fatal infantile lactic acidosis. / Blakely, Emma L.; Rennie, Katherine J.; Jones, Linda; Elstner, Mattias; Chrzanowska-Lightowlers, Zofia M.A.; White, Christopher Bradford; Shield, Julian P.H.; Pilz, Daniela T.; Turnbull, Douglass M.; Poulton, Joanna; Taylor, Robert W.

In: Pediatric Research, Vol. 59, No. 3, 01.03.2006, p. 440-444.

Research output: Contribution to journalArticle

Blakely, EL, Rennie, KJ, Jones, L, Elstner, M, Chrzanowska-Lightowlers, ZMA, White, CB, Shield, JPH, Pilz, DT, Turnbull, DM, Poulton, J & Taylor, RW 2006, 'Sporadic intragenic inversion of the mitochondrial DNA MTND1 gene causing fatal infantile lactic acidosis', Pediatric Research, vol. 59, no. 3, pp. 440-444. https://doi.org/10.1203/01.pdr.0000198771.78290.c4
Blakely EL, Rennie KJ, Jones L, Elstner M, Chrzanowska-Lightowlers ZMA, White CB et al. Sporadic intragenic inversion of the mitochondrial DNA MTND1 gene causing fatal infantile lactic acidosis. Pediatric Research. 2006 Mar 1;59(3):440-444. https://doi.org/10.1203/01.pdr.0000198771.78290.c4
Blakely, Emma L. ; Rennie, Katherine J. ; Jones, Linda ; Elstner, Mattias ; Chrzanowska-Lightowlers, Zofia M.A. ; White, Christopher Bradford ; Shield, Julian P.H. ; Pilz, Daniela T. ; Turnbull, Douglass M. ; Poulton, Joanna ; Taylor, Robert W. / Sporadic intragenic inversion of the mitochondrial DNA MTND1 gene causing fatal infantile lactic acidosis. In: Pediatric Research. 2006 ; Vol. 59, No. 3. pp. 440-444.
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