Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder

Science. 1999 Jan 29;283(5402):689-92. doi: 10.1126/science.283.5402.689.


Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive human disease associated with multiple deletions of skeletal muscle mitochondrial DNA (mtDNA), which have been ascribed to a defect in communication between the nuclear and mitochondrial genomes. Examination of 12 MNGIE probands revealed homozygous or compound-heterozygous mutations in the gene specifying thymidine phosphorylase (TP), located on chromosome 22q13.32-qter. TP activity in leukocytes from MNGIE patients was less than 5 percent of controls, indicating that loss-of-function mutations in TP cause the disease. The pathogenic mechanism may be related to aberrant thymidine metabolism, leading to impaired replication or maintenance of mtDNA, or both.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Chromosomes, Human, Pair 22 / genetics
  • DNA, Mitochondrial / genetics
  • DNA, Mitochondrial / metabolism
  • Exons
  • Gastrointestinal Motility
  • Humans
  • Introns
  • Mitochondria, Muscle / genetics
  • Mitochondrial Encephalomyopathies / enzymology
  • Mitochondrial Encephalomyopathies / genetics*
  • Molecular Sequence Data
  • Mutation*
  • Mutation, Missense
  • Neovascularization, Physiologic
  • Polymorphism, Genetic
  • RNA Splicing
  • Sequence Deletion
  • Thymidine / metabolism
  • Thymidine Phosphorylase / chemistry
  • Thymidine Phosphorylase / genetics*
  • Thymidine Phosphorylase / metabolism


  • DNA, Mitochondrial
  • Thymidine Phosphorylase
  • Thymidine