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Thymidine Phosphorylase Gene Mutations in MNGIE, a Human Mitochondrial Disorder

Science  29 Jan 1999:
Vol. 283, Issue 5402, pp. 689-692
DOI: 10.1126/science.283.5402.689

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Abstract

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.

  • * To whom correspondence should be addressed. E-mail: mh29{at}columbia.edu

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