Thymidine phosphorylase mutations cause instability of mitochondrial DNA

Michio Hirano, Clotilde Lagier-Tourenne, Maria L. Valentino, Ramon Martí, Yutaka Nishigaki

Research output: Contribution to journalArticlepeer-review


Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder characterized by ptosis and progressive external ophthalmoplegia, peripheral neuropathy, severe gastrointestinal dysmotility, cachexia and leukoencephalopathy. Muscle biopsies of MNGIE patients have revealed morphologically abnormal mitochondria and defects of respiratory chain enzymes. In addition, patients harbor depletion, multiple deletions, and point mutations of mitochondrial DNA (mtDNA). This disorder is caused by loss-of-function mutations in the gene encoding thymidine phosphorylase (TP) a cytosolic enzyme. In MNGIE patients, TP activity is very low or absent resulting in dramatically elevated levels of plasma thymidine and deoxyuridine. We have hypothesized that the increased levels of thymidine and deoxyuridine cause mitochondrial nucleotide pool imbalances that, in turn, generate mtDNA alterations.

Original languageEnglish
Pages (from-to)152-156
Number of pages5
Issue number1-2 SPEC. ISS.
Publication statusPublished - Jul 18 2005


  • Mitochondrial DNA
  • Nucleoside
  • Nucleotide
  • Thymidine phosphorylase

ASJC Scopus subject areas

  • Genetics


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