SURF1基因两个新突变致Leigh综合征1例  

Two novel mutations on SURF1 gene identified in a Chinese patient with Leigh Syndrome

作　　者：孙芳[1] 杨艳玲[1] 王朝霞[2] 戚豫[3] 宋金青[1] 钱宁[1] 姜玉武[1] 肖江喜[4] 秦炯[1] 吴希如[1] 

机构地区：[1]北京大学第一医院儿科,北京100034 [2]北京大学第一医院神经内科,北京100034 [3]北京大学第一医院中心实验室,北京100034 [4]北京大学第一医院放射影像科,北京100034

出　　处：《中国医刊》2006年第5期25-27,共3页Chinese Journal of Medicine

基　　金：北京大学人类疾病基因研究中心科研基金(2001-02);国家自然科学基金面上项目(30471832);卫生部临床学科重点项目资助(2001-0912)

摘　　要：目的研究1例因常染色体Surfe it 1(SURF1)基因2个新突变所致Le igh综合征女童的临床及其突变特点。方法患儿为第一胎,生后运动发育落后,4岁时出现肢体震颤,进行性加重,伴运动倒退。4岁6个月来院时不能独站,左侧肢体痉挛性瘫痪,血乳酸、丙酮酸增高,腓肠肌活检未见异常。脑MR I显示双侧基底节、小脑脚上交叉多发性软化灶,符合Le igh综合征诊断。患者曾口服安坦、维生素B1等药物无效,12岁死于肺炎、呼吸衰竭。本研究运用聚合酶链式反应扩增SURF1基因的9个外显子序列,对患儿及103名正常人的外周血白细胞DNA进行正反向序列测定检测突变。结果患者线粒体基因筛查未见异常,SURF1基因测序发现了分别位于内含子3的240+1G>C剪切位点突变和外显子6的574C>G错义突变两个杂合性新突变。结论细胞色素C氧化酶缺陷是Le igh综合征的常见原因,本研究通过对1例中国Le igh综合征患者的SURF1基因分析,首次发现了240+1G>C和574C>G两个新突变,不仅明确了患者病因,并将进一步充实人类Le igh综合征致病基因库。Objective Leigh syndrome is a severe early-onset progressive neurodegenerative disorder due to mitochondrial oxidative phosphorylation defects. This study aimed to investigate the clinical and mutational characteristics of a girl with Leigh syndrome due to two novel mutations of SURF1. Methods The proband was the first child of her parents. Her psychomotor development was delayed from her infant period. She developed tremor, left paraplegia and progressive movement retrogression at the age of 4 years. She could not stand when she was hospitalized at the age of 4.5 years. Her blood lactate and pyruvate were significantly elevated. Symmetric bilateral basal ganglion and brain stem lesions characterized by hyperintensity on her cranial MRI T2-weighted images and low intensity on T2-weighted images were found. The proband showed gradually degeneration and died of respiratory failure induced by pneumonia at the age of 12 years. Genomic DNA from peripheral blood leucocytes was collected for genetic analysis from the proband and 103 normal controis. All of the nine exons of SURF1 were amplified by polymerase chain reaction （PCR）. Forward and reverse sequencing was performed for mutation analysis. Results Mitochondrial gene mutations were excluded. Two novel heterozygous mutations, 240 ＋ 1G 〉 C and 574C 〉 G on SURF1 gene were identified in the patient while no mutations were identified in the normal controls. Conclusions Leigh Syndrome associated with COX deficiency is commonly due to the mutations of SURF1 gene. Through the genetic analysis of SURF1 gene in a Chinese patient with Leigh syndrome, two novel mutations of 240 ＋ 1G 〉 C and 574C 〉 G were firstly reported. This study will be helpful for identifying the etiology and enriching the mutation database of Leigh syndrome.

关 键 词：亚急性坏死性脑脊髓病(Leigh综合征) 细胞色素C氧化酶 SURF1基因 新突变 

分 类 号：R725.8[医药卫生—儿科]