线粒体ND1基因T3866C突变可能是Leber's遗传性 视神经病和四肢畸形跛行相关的突变

doi:10.3724/SP.J.1005.2010.00141

遗传 ›› 2010, Vol. 32 ›› Issue (2): 141-147.doi: 10.3724/SP.J.1005.2010.00141

线粒体ND1基因T3866C突变可能是Leber's遗传性视神经病和四肢畸形跛行相关的突变

刘燕^{1, 2}, 庄淑流³, 童绎⁴, 瞿佳², 周翔天², 赵福新², 张娟娟², 张永梅^{1, 2}, 章豫^{1, 2}, 管敏鑫^{1, 5, 6}

1. 温州医学院浙江省医学遗传学重点实验室, 温州 325035; 2. 温州医学院附属眼视光医院, 温州 325027; 3. 福州东南眼科医院, 福州 350004; 4. 福建医科大学附属第一医院, 福州 350005; 5. Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; 6. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA

收稿日期:2009-09-12 修回日期:2009-11-24 出版日期:2010-02-20 发布日期:2010-01-15
通讯作者: 管敏鑫 E-mail:gminxin88@gmail.com
基金资助:
浙江省自然科学基金重大项目(编号：Z204492), 国家杰出青年科学基金及海外、港澳青年学者合作研究基金项目(编号：30628013)和浙江省自然科学基金项目(编号：Y2090649)资助

Leber's hereditary optic neuropathy and limbs abnormity claudication may be associated with the mitochondrial ND1 T3866C mutation

LIU Yan^{1, 2}, ZHUANG Shu-Liu³, TONG Yi⁴, QU Jia², ZHOU Xiang-Tian², ZHAO Fu-Xin², ZHANG Juan-Juan², ZHANG Yong-Mei^{1, 2}, ZHANG Yu^{1, 2}, GUAN Min-Xin^{1, 5, 6}

1. Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou 325035, China; 2. School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou 325027, China; 3. Fuzhou Southeastern Eye Hospital, Fuzhou 350004, China; 4. The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China; 5. Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati OH 45229, USA; 6. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati OH 45229, USA

Received:2009-09-12 Revised:2009-11-24 Online:2010-02-20 Published:2010-01-15
Contact: GUAN Min-Xin1 E-mail:gminxin88@gmail.com

摘要/Abstract

摘要：

线粒体DNA(Mitochondrial DNA, mtDNA)突变与人类许多疾病的发病机制相关。现报道1个具有典型母系遗传特征的中国人Leber's遗传性视神经病和四肢畸形跛行的家系。该家系共5代60人, 共27名母系成员, 其中4人只有Leber’s遗传性视神经病症状, 1人呈现四肢畸形跛行症状, 4人同时具有上述两种临床症状, 而其他成员无临床症状。对先证者的mtDNA全序列进行分析, 发现ND1基因T3866C突变位点和43个多态位点, 经系统进化树分析属于东亚单体型D4a3。MtDNA ND1 3866位点T-C碱基的改变使ND1亚基第187位进化高度保守的异亮氨酸转变为苏氨酸, 从而改变该蛋白的结构, 进而影响其功能。在135名正常对照中未发现该突变。因此, 线粒体ND1 T3866C可能是与Leber’s遗传性视神经病和四肢畸形跛行相关的线粒体基因突变

关键词: Leber's遗传性视神经病变, 线粒体DNA, 突变, 视力障碍, 四肢畸形跛行

Abstract:

Mutations in mitochondrial DNA have been associated with a wide spectrum of clinical abnormalities. We reported here the clinical, genetic and molecular characterization of a five-generation Han Chinese pedigree with Leber’s Hereditary Optic Neuropathy (LHON) and limbs abnormity claudication. Of 27 matrilineal relatives, four exhibited only LHON, one suffered from only limbs abnormity claudication, and four had both LHON and limbs abnormity claudication. Sequence analysis of mitochondrial genome in this family identified the known T3866C mutation in ND1 gene and other 43 variants belonging to the Asian haplogroup D4a3. The T3866C (I187T) mutation resulted in the replacement of isoleucine at position 187 with theronine. The isoleucine at position 187 located at one of transmembrane domain in ND1 polypeptide. The isoleucine at position 187 was extremely conserved among 29 organisms, while other variants showed no evolutionarily conservation. Furthermore, the T3866C was absence in 135 Chinese control subjects. The T3866C mutation likely alters the complex I activity, which causes mitochondrial dysfunction associated with LHON and limbs abnormity claudication. Therefore, the T3866C mutation is likely associated with LHON and limbs abnormity claudication.

Key words: Leber's hereditary optic neuropathy, mitochondrial DNA, mutation, vision loss, limbs abnormity claudication

刘燕，庄淑流，童绎，瞿佳，周翔天，赵福新，张娟娟，张永梅，章豫. 线粒体ND1基因T3866C突变可能是Leber's遗传性视神经病和四肢畸形跛行相关的突变[J]. 遗传, 2010, 32(2): 141-147.

LIU Yan, PENG Chu-Liu, TONG Shi, JI Jia, ZHOU Xiang-Tian, DIAO Fu-Xin, ZHANG Juan-Juan, ZHANG Yong-Mei, ZHANG Shu. Leber's hereditary optic neuropathy and limbs abnormity claudication may be associated with the mitochondrial ND1 T3866C mutation[J]. HEREDITAS, 2010, 32(2): 141-147.

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线粒体ND1基因T3866C突变可能是Leber's遗传性视神经病和四肢畸形跛行相关的突变

Leber's hereditary optic neuropathy and limbs abnormity claudication may be associated with the mitochondrial ND1 T3866C mutation

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线粒体ND1基因T3866C突变可能是Leber's遗传性 视神经病和四肢畸形跛行相关的突变

Leber's hereditary optic neuropathy and limbs abnormity claudication may be associated with the mitochondrial ND1 T3866C mutation

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线粒体ND1基因T3866C突变可能是Leber's遗传性视神经病和四肢畸形跛行相关的突变