机构：[1]Institute of Genetics, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China[2]Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China[3]Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical University, Wenzhou, Zhejiang, China[4]School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, China[5]Department of Ophthalmology, Xingtai Eye Hospital, Xingtai, Hebei, China[6]Department of Ophthalmology, The Third Affiliated Hospital, Xinxiang Medical College, Xinxiang, Henan, China[7]Department of Ophthalmology, Dongfang Hospital, Beijing University of Chinese Medicine and Pharmacology, Beijing, China[8]Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States[9]School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China
To investigate the prevalence and spectrum of mitochondrial ND4 mutations in subjects with Leber's hereditary optic neuropathy (LHON).A cohort of 1281 Chinese Han probands and 478 control subjects underwent clinical and genetic evaluation, and sequence analysis of mitochondrial (mt) DNA, as well as enzymatic assay of NADH:ubiquinone oxidoreductase.In this cohort, 503 probands had a family history of optic neuropathy and 778 subjects were sporadic cases. Mutational analysis of ND4 gene identified 149 (102 known and 47 novel) variants. The prevalence of known m.11778G>A mutation was 35.36%. Furthermore, we identified the known m.11696G>A and m.11253T>C mutations and five novel putative LHON-associated mutations. These mutations accounted for 2.74% of cases of LHON subjects. By enzymatic assay, we showed a mild decrease in the activity of NADH:ubiquinone oxidoreductase in mutant cell lines carrying only one putative mtDNA mutation. The low penetrance of optic neuropathy and mild biochemical defects in these pedigrees carrying only m.11696G>A mutation and one putative LHON-associated mutation suggested that the mutation(s) is(are) necessary but is(are) itself(themselves) insufficient to produce a visual failure. Moreover, mtDNAs in 169 probands carrying the LHON-associated mutation(s) were widely dispersed among 13 Eastern Asian haplogroups. In particular, the frequencies of haplogroups D, M8, M10, M11, and H in probands carrying the LHON-associated mtDNA mutation(s) were higher than those in Chinese controls.These results suggested that the ND4 gene is the hot spot for mutations associated with LHON. Thus, these findings may provide valuable information for the further understanding of pathogenic mechanism of LHON.
基金：
National Key Technologies R&D Program Grant
2012BAI09B03 from the Ministry of Science and Technology of
China (MXG and PJ) and Grants 81200724, 31471191, and
81400434 from the National Nature Science Foundation of China
(MXG, JZ, YJ), and the Ministry of Education of Zhejiang Provincial
Program Y201017001 and the Ministry of Science and Technology
of Wenzhou City Y20100272 (ML).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2014]版：
大类|2 区医学
小类|2 区眼科学
最新[2025]版：
大类|2 区医学
小类|2 区眼科学
第一作者：
第一作者机构：[1]Institute of Genetics, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China[2]Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China
共同第一作者：
通讯作者：
通讯机构：[1]Institute of Genetics, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China[2]Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China[8]Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States[9]School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China[*1]Institute of Genetics, School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China
推荐引用方式(GB/T 7714)：
Pingping Jiang,Min Liang,Juanjuan Zhang,et al.Prevalence of Mitochondrial ND4 Mutations in 1281 Han Chinese Subjects With Leber's Hereditary Optic Neuropathy.[J].Investigative ophthalmology & visual science.2015,56(8):4778-88.doi:10.1167/iovs.14-16158.
APA：
Pingping Jiang,Min Liang,Juanjuan Zhang,Yinglong Gao,Zheyun He...&Min-Xin Guan.(2015).Prevalence of Mitochondrial ND4 Mutations in 1281 Han Chinese Subjects With Leber's Hereditary Optic Neuropathy..Investigative ophthalmology & visual science,56,(8)
MLA：
Pingping Jiang,et al."Prevalence of Mitochondrial ND4 Mutations in 1281 Han Chinese Subjects With Leber's Hereditary Optic Neuropathy.".Investigative ophthalmology & visual science 56..8(2015):4778-88
医学