Mitochondrial ND6 T14502C variant may modulate the phenotypic expression of LHON-associated G11778A mutation in four Chinese families |
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Authors: | Juanjuan Zhang Xiangtian Zhou Jian Zhou Chengwu Li Fuxin Zhao Yan Wang Jiying Wang Wanshi Cai Yi Tong Yan-Hong Sun Jia Qu Min-Xin Guan |
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Institution: | a School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang, China b Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang, China c Department of Ophthalmology, Dongfang Hospital, Beijing University of Chinese Medicine and Pharmacology, Beijing, China d Department of Ophthalmology, Eye Hospital, Chinese Academy of China Medical Science, Beijing, China e The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China f Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA g Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA |
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Abstract: | We report here the clinical, genetic, and molecular evaluations of four Han Chinese families with Leber’s hereditary optic neuropathy. Thirty-one (20 males/11 females) of 83 matrilineal relatives in these families exhibited the variable severity and age-at-onset in visual impairment. The average age-of-onset of vision loss was 22 years old. Strikingly, these penetrances of visual impairment in these Chinese families were higher than those in other 11 Chinese pedigrees carrying the only ND4 G11778A mutation. Molecular analysis identified the known G11778A mutation and distinct sets of variants belonging to the Asian haplogroups M10a and M7c2. Of these, the T14502C mutation caused the substitution of a highly conserved isoleucine for valine at position 58 in ND6. This mutation has been associated with LHON in other Chinese families with very low penetrance of LHON. Thus, the deficient activities of complex I, caused by G11778A mutation, would be worsened by the T14502C mutation in these four Chinese families. As a result, mitochondrial dysfunctions would lead to the high penetrance and expressivity of visual loss in these Chinese families carrying both G11778A and T14502C mutations than other 11 Chinese families carrying only G11778A mutation. These data suggested that the T14502C variant may modulate the phenotypic manifestation of the G11778A mutation in these Chinese pedigrees. |
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Keywords: | Leber&rsquo s hereditary optic neuropathy Mitochondrial DNA Mutation Variant Modifier Chinese |
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