线粒体tRNA A14693G可能是与Leber遗传性视神经病变相关的基因突变

doi:10.3724/SP.J.1005.2010.00353

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HEREDITAS ›› 2010, Vol. 32 ›› Issue (4): 353-359.doi: 10.3724/SP.J.1005.2010.00353

Leber’s hereditary optic neuropathy may be associated with the mi-tochondrial tRNA A14693G mutation in three Chinese families

ZHANG Yong-Mei^{1, 2}, JI Yan-Chun^{1, 2}, LIU Xiao-Ling², ZHOU Xiang-Tian², ZHAO Fu-Xin², SUN Yan-Hong³, WEI Qi-Ping³, ZHANG Juan-Juan², LIU Yan^{1, 2}, QU Jia2, GUAN Min-Xin^{1, 4, 5}

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. Department of Ophthalmology, Dongfang Hospital, Beijing University of Chinese Medicine and Pharmacology, Beijing 100078, China;
4. Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati OH 45229, USA;
5. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati OH 45229, USA

Received:2009-09-17 Revised:2010-01-29 Online:2010-04-20 Published:2010-03-24
Contact: GUAN Min-Xin E-mail:gminxin88@gmail.com

Abstract

Abstract: We reported here the clinical, genetic and molecular characterization of three Han Chinese families with Leber’s hereditary optic neuropathy. Ophthalmologic examinations revealed the variable severity and age-at-onset of visual loss among probands and other matrilineal relatives of these families. Strikingly, these families exhibited extremely low penetrances of visual impairment. Sequence analysis of complete mitochondrial genomes in these pedigrees identified the known homoplasmic tRNA^Glu A14693G mutation and distinct sets of polymorphism belonging to haplogroups Y1b, Y1 and Y1, respectively. The A14693G mutation occurs at the extremely conserved nucleotide (conventional position 54) of tRNAGlu. Thus, this mutation may alter structural formation and stabilization of functional tRNAs, thereby leading to a failure in tRNA metabolism and mitochondrial dysfunction involved in visual impairment. However, none of other variants showed the evolutionary conservation and functional significance. These observations suggested that the tRNA^Glu A14693G mutation may be involved in the pathogenesis of optic neuropathy in these families.

Key words: Leber's hereditary optic neuropathy, mitochondrial DNA, visual failure, mutation

ZHANG Yong-Mei, JI Yan-Chun, LIU Xiao-Ling, ZHOU Xiang-Tian, DIAO Fu-Xin, SUN Yan-Gong, HUI Qi-Beng, ZHANG Juan-Juan, LIU Yan, JI Jia, GUAN Min-Xin. Leber’s hereditary optic neuropathy may be associated with the mi-tochondrial tRNA A14693G mutation in three Chinese families[J]. HEREDITAS, 2010, 32(4): 353-359.

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Leber’s hereditary optic neuropathy may be associated with the mi-tochondrial tRNA A14693G mutation in three Chinese families

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