线粒体基因G13513A突变导致的线粒体脑肌病六例临床表型分析  

Phenotype in 6 patients with mitochondrial DNA G13513A mutation

作　　者：王朝霞[1] 赵丹华[1] 戚晓昆[2] 韩漫夫[3] 冯立群[4] 袁云[1] 

机构地区：[1]北京大学第一医院神经内科,100034 [2]海军总医院神经内科 [3]广东省深圳市第二人民医院神经内科 [4]首都医科大学附属北京安贞医院神经内科

出　　处：《中华神经科杂志》2011年第5期322-326,共5页Chinese Journal of Neurology

基　　金：国家自然科学基金资助项目（30870864）,志谢 感谢日本国立神经精神研究所疾病研究第二部的後藤雄一教授在分子生物学检测方面给予的帮助

摘　　要：目的报告6例mtDNA G13513A点突变引起的线粒体脑肌病患者的临床、影像学特点，总结mtDNA G13513A突变所致的线粒体病的临床表型。方法对35例mtDNA常见突变（包括大片段缺失及A3243G、T3271C、A8344G、T8993G／C点突变）检查为阴性的线粒体脑肌病患者，用线粒体DNA全长测序和（或）聚合酶链反应-限制性片段长度多态法检测mtDNA G13513A点突变，分析阳性患者的临床特点，复习文献报道的mtDNA G13513A所致线粒体病的病例。结果35例患者中有6例存在mtDNA G13513A突变。该6例患者均出现偏盲、轻偏瘫或偏身感觉障碍等卒中样发作表现，其中3例成人发病者以卒中样发作为主要症状，伴随癫痫、头痛、身材矮小、神经性耳聋等，头颅MRI显示以顶．枕-颞叶受累为主的大片病灶，符合成人型线粒体脑肌病伴高乳酸血症和卒中样发作（MELAS）的临床和影像学特点；3例青少年发病者除卒中样发作外，还有构音障碍、共济失调、眼外肌瘫痪等脑干受累的症状，MRI检查可见枕一颞叶大脑皮质非对称性病灶，以及双侧基底节和脑干的对称性病灶，符合青少年型MELAS—Leigh叠加综合征的临床和影像学特点。肌肉病理检查在5例患者发现不整红边纤维。经复习文献，发现mtDNA G13513A突变患者还存在婴幼儿型Leigh或Leigh样综合征表型。结论mtDNA G13513A点突变是线粒体脑肌病较常见的致病性突变，主要导致Leigh综合征、MELAS—Leigh叠加综合征或MELAS综合征，其临床表型具有年龄依赖性。Objective To report 6 Chinese patients with mitochondrial encephalomyopathy caused by mitochondrial DNA （mtDNA） G13513A mutation and discuss the mitochondrial phenotype associated with this mutation based on the data of our patient series as well as the reports by others. Methods Direct sequencing of polymerase chain reaction （PCR） products or PCR-RFLP analysis was performed to screen mtDNA G13513A mutation in 35 cases with mitochondrial encephalomyopathy, who carried no mtDNA common mutations （large scale deletion, A3243G, T3271C, A8344G, or T8993G/C）. The clinical features, MRI changes were retrospectively collected and analyzed. Published studies of all patients with mtDNA G13513A mutation were also reviewed. Results Six patients were identified carrying mtDNA G13513A mutation. All patients presented stroke-like episodes with hemianopsia, hemiparesis or hemiparesthesia. Three adult patients presented clinical and radiological features of adult-onset mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes （MELAS）, including stroke-like episodes, epilepsy, headache, short stature, sensorineural deafness, muhifocal lesions on parietal, occipital and temporal lobes on cranial MRI scans. Three juvenile-onset patients presented the clinical and brain MRI features of MELAS-Leigh syndrome （LS） overlap syndrome. In addition to the stroke-like episodes, they also showed brain stem lesions with dysarthria, ataxia, and ophthalmoplegia. Brain MRI revealed asymmetrical lesions in the cortex of the occipital and temporal lobes, as well as symmetrical lesions in the bilateral basal ganglia and hrainstem. Muslce biopsy showed ragged redfibers in 5 patients. The infant-onset LS or Leigh-like syndrome with mtDNA G13513A was described in the English literature. Conclusions mtDNA G13513A mutation is a common pathogenic mutation for mitochondrial encephalomyopathy, which can result in Leigh syndrome, MELAS-LS overlap syndrome and adult MELAS. The onset of various phenotypes is relativel

关 键 词：线粒体脑肌病 DNA 线粒体 MELAS综合征 LEIGH病 突变 

分 类 号：R746[医药卫生—神经病学与精神病学]