Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder
Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder
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DOI：
10.1126/science.283.5402.689
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发表时间：
1999-01-29
期刊：
影响因子：
56.9
通讯作者：
Hirano, M
中科院分区：
文献类型：
--
作者：
Nishino, I;Spinazzola, A;Hirano, M
线粒体神经胃肠脑肌病(MNGIE)是一种常染色体隐性遗传性疾病，与骨骼肌线粒体DNA(MtDNA)的多次缺失有关，被认为是核基因组和线粒体基因组之间通讯障碍的结果。对12个MNGIE先证者的检查发现，位于染色体22q13.32-QTER上的胸苷磷酸化酶(TP)基因发生纯合子或复合杂合突变。MNGIE患者白细胞中的TP活性不到对照组的5%，表明TP功能丧失突变导致了该病。发病机制可能与胸腺嘧啶核苷代谢异常有关，导致线粒体DNA复制或维持受损，或两者兼而有之。
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.