ND5 is a hot-spot for multiple atypical mitochondrial DNA deletions in mitochondrial neurogastrointestinal encephalomyopathy

Hum Mol Genet. 2004 Jan 1;13(1):91-101. doi: 10.1093/hmg/ddh010. Epub 2003 Nov 12.


Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive multisystem disorder associated with depletion, multiple deletions and site-specific point mutations of mitochondrial DNA (mtDNA). MNGIE is caused by loss-of-function mutations in the gene encoding thymidine phosphorylase (TP; endothelial cell growth factor 1). Deficiency of TP leads to dramatically elevated levels of circulating thymidine and deoxyuridine. The alterations of pyrimidine nucleoside metabolism are hypothesized to cause imbalances of mitochondrial nucleotide pools that, in turn, may cause somatic alterations of mtDNA. We have now identified five major forms of mtDNA deletions in the skeletal muscle of MNGIE patients. While direct repeats and imperfectly homologous sequences appear to mediate the formation of mtDNA deletions, the nicotinamide adenine dinucleotide dehydrogenase 5 gene is a hot-spot for these rearrangements. A novel aspect of the mtDNA deletions in MNGIE is the presence of microdeletions at the imperfectly homologous breakpoints.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence / genetics*
  • Blotting, Southern
  • DNA, Mitochondrial / genetics*
  • Deoxyuridine / metabolism
  • Electron Transport Complex I / genetics*
  • Humans
  • Mitochondrial Encephalomyopathies / genetics*
  • Mitochondrial Proteins
  • Models, Genetic
  • Molecular Sequence Data
  • Muscle, Skeletal / metabolism
  • Polymerase Chain Reaction / methods
  • Sequence Analysis, DNA
  • Sequence Deletion / genetics*
  • Thymidine / metabolism
  • Thymidine Phosphorylase / genetics*


  • DNA, Mitochondrial
  • Mitochondrial Proteins
  • MT-ND5 protein, human
  • Thymidine Phosphorylase
  • Electron Transport Complex I
  • Thymidine
  • Deoxyuridine