Hirano Michio, Lagier-Tourenne Clotilde, Valentino Maria L, Martí Ramon, Nishigaki Yutaka
Department of Neurology, Columbia University College of Physicians and Surgeons, 630 West 168th Street, P&S 4-443, New York, NY 10032, USA.
Gene. 2005 Jul 18;354:152-6. doi: 10.1016/j.gene.2005.04.041.
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.
线粒体神经胃肠性脑肌病（MNGIE）是一种常染色体隐性疾病，其特征为上睑下垂和进行性眼外肌麻痹、周围神经病变、严重的胃肠动力障碍、恶病质和白质脑病。MNGIE患者的肌肉活检显示线粒体形态异常和呼吸链酶缺陷。此外，患者存在线粒体DNA（mtDNA）缺失、多处缺失和点突变。这种疾病是由编码胸苷磷酸化酶（TP，一种胞质酶）的基因突变导致功能丧失引起的。在MNGIE患者中，TP活性非常低或缺失，导致血浆胸苷和脱氧尿苷水平显著升高。我们推测，胸苷和脱氧尿苷水平的升高会导致线粒体核苷酸池失衡，进而引起mtDNA改变。
