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Abstract：
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder associated with mitochondrial alterations. MNGIE is characterized by severe gastrointestinal dysmotility, cachexia, ophthalmoplegia, ptosis, peripheral neuropathy, and leukoencephalopathy. The condition is caused by mutation of the TYMP gene. We studied the clinical and biochemical characteristics of a family with MNGIE. The proband was a 48-year-old male presenting with diarrhea and progressive weight loss. He also had ptosis and exhibited eyeball fixation. His blood and cerebrospinal fluid lactate levels were elevated. Magnetic resonance imaging of the brain revealed diffuse leukoencephalopathy. Ragged red fibers and cytochrome c oxidase-deficient fibers were apparent on muscle biopsy. His vision and ptosis deteriorated significantly during follow-up. Our clinical diagnosis of MNGIE was confirmed by TYMP gene analysis. We discovered a homozygous TYMP c.1193-1216 dup-GGGCGCTGCCGCTGGCGCTGGTGC mutation (a duplication). Some of the family members were heterozygous for the mutation but had no clinical features. We predicted the function of this mutation using PredictProtein and found that the secondary structure had changed in the region of the helix and strand, the transmembrane region, and the protein-protein binding sites. The family described herein exhibited biochemically, genetically, and functionally confirmed MNGIE syndrome.
摘要：
线粒体神经胃肠脑肌病（MNGIE）是一种与线粒体改变相关的常染色体隐性遗传疾病。MNGIE的特点是严重的胃肠动力障碍，恶病质,眼肌麻痹,上睑下垂,周围神经病变,和白质脑病.这种情况是由TYMP基因突变引起的。我们研究了MNGIE家族的临床和生化特征。先证者是一名48岁的男性，表现出腹泻和进行性体重减轻。他还患有眼睑下垂并表现出眼球固定。他的血液和脑脊液乳酸水平升高。脑部磁共振成像显示弥漫性白质脑病。在肌肉活检中明显可见的红色纤维和细胞色素C氧化酶缺陷纤维。在随访期间，他的视力和下垂明显恶化。通过TYMP基因分析证实了我们对MNGIE的临床诊断。我们发现了一个纯合的TYMPc.1193-1216dup-GGGCGCTGCCGCTGGCGCTGTGC突变（重复）。一些家族成员的突变是杂合的，但没有临床特征。我们使用PredictProtein预测了这种突变的功能，发现二级结构在螺旋和链区域发生了变化，跨膜区，和蛋白质-蛋白质结合位点。本文所述的家族表现出生物化学，基因,并在功能上证实MNGIE综合征。
