摘要目的 报道1例由m.10158 T>C突变所致线粒体脑肌病伴高乳酸血症和卒中样发作(mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes,MELAS)叠加Leigh综合征(LS)患者,分析其临床、病理及基因特点.方法 收集患者临床及影像学资料.对患者右侧肱二头肌行活体组织病理检查.通过二代测序+Sanger测序检测患者及其母亲线粒体DNA.利用蛋白质印迹法检测患者肌肉线粒体呼吸链复合物Ⅰ~Ⅳ表达含量.结果 患者女性,40岁,以"反复发作抽搐伴意识不清9个月,再发2 h"入院.头颅MRI检查提示颅内存在大片卒中样病灶,同时合并基底节区对称异常信号影.右侧肱二头肌病理示存在典型不整红边纤维.外周血及肌肉基因检测提示患者存在线粒体DNA m.10158 T>C突变,突变率分别为9.31%及70.0%.蛋白质印迹法检测发现患者肌肉组织内线粒体呼吸链复合物Ⅰ及Ⅳ表达量分别为53.1%±1.2%(正常对照为88.6%±1.7%,t=4.08, P<0.05)及57.3%±2.4%(正常对照为80.1%±2.1%,t=3.39,P<0.05).结论 线粒体m.10158 T>C可引起MELAS/LS叠加综合征,基因检测可能在该病诊断中起到重要作用.

abstractsObjective To report the clinical, myopathological and genetic features of a patient with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS)/Leigh syndrome (LS) overlap syndrome who carried m.10158 T>C mutation. Methods The patient′s clinical and imaging materials were collected. An open biopsy of right biceps brachii was performed. DNA samples were prepared from the patient and her mother′s blood. Direct sequencing of the complete mitochondrial genome was performed to detect the mtDNA mutation.Western blotting was used to estimate the content of respiratory complexes in the patient′s muscle. Results The patient was a 40-year-old female. She had seizures and lost consciousness for 9 months. Brain MRI findings consisted of asymmetrical lesions in the cerebral cortex of the frontal and temporal lobes, as well as symmetrical lesions bilaterally in the basal ganglia. Muscle biopsy showed typical ragged red fibers. Direct sequencing of the complete mitochondrial genome from blood and muscle of the patient revealed the T-to-C transition at nucleotide position 10158 in the MT-ND3 gene.The mutation rate was 9.31% and 70.0%, respectively.Western blotting demonstrated that the contents of complexes Ⅰ and Ⅳ were significantly lower in the patient′s muscle mitochondria compared with the normal controls (53.1%±1.2% vs 88.6%±1.7%, t=4.08, P<0.05;57.3%±2.4% vs 80.1%±2.1%, t=3.39,P<0.05).Conclusion We reported a case of MELAS/LS overlap syndrome who carried m.10158 T>C mutation in MT-ND3 gene and DNA test is very important for the diagnosis of the disease.