Thymidine Phosphorylase Gene Mutations in MNGIE, a Human Mitochondrial Disorder

作者：Ichizo Nishino, Antonella Spinazzola, Michio Hirano · 发表于：Science · 年份：1999 · DOI：10.1126/science.283.5402.689 · 被引用次数：902 · 研究领域：Mitochondrial Function and Pathology、Metabolism and Genetic Disorders、Biochemical and Molecular Research

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.