Yang Yan-ling, Sun Fang, Zhang Yao, Qian Ning, Yuan Yun, Wang Zhao-xia, Qi Yu, Xiao Jiang-xi, Wang Xiao-ying, Qi Zhao-yue, Zhang Yue-hua, Jiang Yu-wu, Bao Xin-hua, Qin Jiong, Wu Xi-ru
Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
Chin Med J (Engl). 2006 Mar 5;119(5):373-7.
Leigh syndrome is an inherited neurodegenerative disease that emerges in infancy and childhood and presents with a clinically heterogeneous variety of neuromuscular and non-neuromuscular disorders. It can result from the inheritance of mutations in either nuclear or mitochondrial DNA. In the current study, we performed a retrospective study in 65 patients in order to investigate the clinical and genetic characteristics of Leigh syndrome in Chinese patients.
Sixty-five unrelated cases (35 men and 30 women) who were hospitalized in the past 12 years were reviewed. Diagnosis was based on both the clinical presentation and the characteristic neuropathologic findings of bilateral symmetric necrotizing lesions in the basal ganglia and brain stem as detected using cranial computed tomography (CT) scan or magnetic resonance imaging (MRI). The differential diagnosis of organic acidurias and fatty acid beta-oxidation defects were performed. Specific point mutations and deletions in mitochondrial DNA (T8993G, T8993C, T9176C, A8344G, A3243G) were screened by PCR-restriction analysis and Southern blot. The SURF1 gene was sequenced. Skeletal muscle biopsies were performed in 17 (26.2%) of the patients. The diagnosis was confirmed by autopsy in 6 (9.2%) patients.
The patients had various forms of metabolic encephalomyopathy. Fifty-nine (90.8%) of the patients had the typical neuroradiological features of Leigh syndrome, including symmetrical necrotizing lesions scattered within the basal ganglia, thalamus and brain stem. Twenty (30.8%) patients were confirmed by genetic, biochemical analysis and autopsy. Specific point mutations in mitochondrial DNA were found in 5 cases (7.7%). Of these, the A8344G mutation was detected in 2 patients. The T8993G, T8993C, and A3243G point mutations were identified in 3 other patients, respectively. SURF1 mutations associated with cytochrome c oxidase deficiency were identified in 8 (12.3%) families by DNA sequencing. A G604C mutation was identified in 6 (9.2%) patients. The genotypes of 52 patients remained unknown.
Leigh syndrome presents as a diverse array of clinical features and can result from specific mutations in nuclear or mitochondrial DNA. In this study, SURF1 mutations associated with cytochrome c oxidase deficiency were identified in 8 (12.3%) out of 65 patients with Leigh syndrome. It indicates that SURF1 mutations might be a common cause of Leigh syndrome in China. The etiology of Leigh syndrome in Chinese patients represents a persistent challenge to clinicians.
Leigh综合征是一种遗传性神经退行性疾病，在婴儿期和儿童期发病，表现为临床异质性的各种神经肌肉和非神经肌肉疾病。它可由核DNA或线粒体DNA的突变遗传引起。在本研究中，我们对65例患者进行了回顾性研究，以调查中国患者中Leigh综合征的临床和遗传特征。
回顾过去12年住院的65例无关病例（35例男性和30例女性）。诊断基于临床表现以及使用头颅计算机断层扫描（CT）或磁共振成像（MRI）检测到的基底神经节和脑干双侧对称坏死性病变的特征性神经病理学发现。进行了有机酸尿症和脂肪酸β氧化缺陷的鉴别诊断。通过PCR限制性分析和Southern印迹筛选线粒体DNA中的特定点突变和缺失（T8993G、T8993C、T9176C、A8344G、A3243G）。对SURF1基因进行测序。17例（26.2%）患者进行了骨骼肌活检。6例（9.2%）患者通过尸检确诊。
患者有多种形式的代谢性脑肌病。59例（90.8%）患者具有Leigh综合征典型的神经放射学特征，包括散在分布于基底神经节、丘脑和脑干的对称性坏死性病变。20例（30.8%）患者通过遗传学、生化分析和尸检确诊。线粒体DNA中发现特定点突变5例（7.7%）。其中，2例患者检测到A8344G突变。另外3例患者分别鉴定出T8993G、T8993C和A3243G点突变。通过DNA测序在8个（12.3%）家系中鉴定出与细胞色素c氧化酶缺乏相关的SURF1突变。6例（9.2%）患者鉴定出G604C突变。52例患者的基因型仍未知。
Leigh综合征表现为多种多样的临床特征，可由核DNA或线粒体DNA的特定突变引起。在本研究中，65例Leigh综合征患者中有8例（12.3%）鉴定出与细胞色素c氧化酶缺乏相关的SURF1突变。这表明SURF1突变可能是中国Leigh综合征的常见病因。中国患者中Leigh综合征的病因对临床医生来说仍然是一个持续的挑战。
