Leber's hereditary optic neuropathy is potentially associated with a novel m.5587T>C mutation in two pedigrees

Ji,Yanchun; Qiao,Lihua; Liang,Xiaoyang; Zhu,Ling; Gao,Yinglong; Zhang,Juanjuan; Jia,Zidong; Wei,Qi‑Ping; Liu,Xiaoling; Jiang,Pingping; Guan,Min‑Xin

doi:10.3892/mmr.2017.7734

Leber's hereditary optic neuropathy is potentially associated with a novel m.5587T>C mutation in two pedigrees

Authors:
- Yanchun Ji
- Lihua Qiao
- Xiaoyang Liang
- Ling Zhu
- Yinglong Gao
- Juanjuan Zhang
- Zidong Jia
- Qi‑Ping Wei
- Xiaoling Liu
- Pingping Jiang
- Min‑Xin Guan
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Affiliations: Division of Clinical Genetics and Genomics, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China, School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang 325025, P.R. China, Institute of Genetics, Zhejiang University and Department of Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China, Department of Ophthalmology, Beijing University of Chinese Medicine, Beijing 100029, P.R. China
Published online on: October 5, 2017 https://doi.org/10.3892/mmr.2017.7734
Pages: 8997-9004

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Abstract

Mitochondrial (mt)DNA mutations have been revealed to be associated with Leber's hereditary optic neuropathy (LHON). The present study conducted clinical, genetic and molecular evaluations of two Han Chinese families. A total of 4 (3 men and 1 female) out of 14 matrilineal relatives in the families exhibited visual impairment with variable severity and age of onset. The average age of onset of visual loss was 20.5 years old. Molecular analysis of the complete mitochondrial genome in these pedigrees demonstrated that the three primary mutations associated with LHON were not detected; however, the homoplasmic m.5587T>C mutation was identified, which was localized at the end of the mitochondrially encoded transfer (t)RNA alanine gene and may alter the tertiary structure of this tRNA. Subsequently, this structural alteration may result in tRNA metabolism failure. In addition, distinct sets of mtDNA polymorphisms belonging to haplogroup F1 were detected in both families tested. The findings of the present study suggested that the m.5587T>C mutation may be involved in the pathogenesis of visual impairment. In addition, the mtDNA variant m.15024G>A(p.C93H) in the mitochondrially encoded cytochrome B gene was detected in both families, which exhibited evolutionary conservation, indicating it may serve a potential modifying role in the development of visual impairment associated with m.5587T>C mutation in these families. Furthermore, other modifying factors, including nuclear modifier genes, and environmental and personal factors may also contribute to the development of LHON in subjects carrying this mutation.

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