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

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

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

Abstract

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

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

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