论文部分内容阅读
目的本文报道1例由于ND3基因突变导致线粒体呼吸链复合物Ⅰ缺陷的患儿。该患儿自6岁起出现眼睑下垂、无力、癫癎及运动倒退,呈进行性加重。血液乳酸、丙酮酸增高,脑MRI示双侧基底节对称性损害,符合Leigh综合征诊断。为明确病因,提取患儿和父母的外周血白细胞线粒体蛋白,进行氧化磷酸化酶复合物Ⅰ～V活性测定,并提取DNA,分析编码线粒体呼吸链复合物Ⅰ的7个线粒体结构基因。结果显示患儿线粒体呼吸链复合物Ⅰ活性为33.1 nmol/min.毫克线粒体总蛋白(正常对照44.0±5.4 nmol/min.毫克线粒体总蛋白),复合物Ⅰ与柠檬酸合酶活性比值为19.8%(正常对照48.1%±11.0%),均降低。复合物Ⅱ～V活性正常。患儿线粒体ND3基因10191T>C突变。其父母线粒体基因及呼吸链复合物酶活性正常。治疗后,现患者16岁,癫癎控制良好,双下肢痉挛性瘫痪,智力正常。通过外周血白细胞线粒体氧化磷酸化酶复合物活性测定及基因分析,本研究首次诊断了编码线粒体呼吸链复合物Ⅰ亚基的ND3基因10191T>C突变导致复合物Ⅰ缺陷,为Leigh综合征的发病原因提供依据。
OBJECTIVE: This paper reports a case of a child with mitochondrial respiratory chain complex I deficiency due to mutations in the ND3 gene. The child from the age of 6 appeared ptosis, weakness, epilepsy and motor regress, was progressive increase. Blood lactate, pyruvate increased brain MRI showed bilateral basal ganglia symmetry damage, in line with Leigh syndrome diagnosis. To clarify the etiology, the mitochondrial proteins of peripheral blood leukocytes in children and their parents were extracted and the activity of oxidative phosphorylase I ~ V was determined. DNA was extracted and the seven mitochondrial structural genes encoding mitochondrial respiratory chain complex Ⅰ were analyzed. The results showed that the activity of mitochondrial respiratory chain complex I in children was 33.1 nmol / min. The total mitochondrial protein (44.0 ± 5.4 nmol / min. Mg of mitochondrial total protein in normal control), the ratio of complex I to citrate synthase activity was 19.8% (48.1% ± 11.0% of the normal control), all decreased. Complex Ⅱ ~ V activity is normal. Children with mitochondrial ND3 gene 10191T> C mutation. The parents of mitochondrial genes and respiratory chain complex enzyme activity. After treatment, the patient is 16 years old, control of epilepsy, paralysis of both lower extremities spasticity, mental retardation. Through the activity determination of leukocyte mitochondrial oxidative phosphorylase complex in peripheral blood and gene analysis, this study for the first time diagnosed the mutation of 10191T> C of ND3 gene, which encodes the subunit of mitochondrial respiratory chain complex Ⅰ, resulting in complex Ⅰ deficiency, which is the cause of Leigh syndrome Reason to provide basis.