Novel mutation of ND4 gene identified by targeted next-generation sequencing in patient with Leigh syndrome

doi:10.1038/jhg.2016.127

	Novel mutation of ND4 gene identified by targeted next-generation sequencing in patient with Leigh syndrome
	Xu, Bing 1; Li, Xiyuan 2,3; Du, Miaomiao 1; Zhou, Chao 1; Fang, Hezhi 1; Lyu, Jianxin 1; Yang, Yanling 2
	2017-02-01
发表期刊	JOURNAL OF HUMAN GENETICS
ISSN	1434-5161
卷号	62 期号:2 页码:291-297
摘要	By using next-generation sequencing targeted to MitoExome including the entire mtDNA and exons of 1033 genes encoding the mitochondrial proteome, we described here a novel m. 11240C>T mutation in the mitochondrial ND4 gene from a patient with Leigh syndrome. High mutant loads of m. 11240C>T were detected in blood, urinary epithelium, oral mucosal epithelium cells, and skin fibroblasts of the patient. Decreased mitochondrial complex I activity was found in transmitochondrial cybrids containing the m. 11240C>T mutation with biochemical analysis. Furthermore, functional investigations confirmed that mitochondria with the m. 11240C>T variant exhibited lower adenosine triphosphate-related mitochondrial respiration. However, complex I assembly in mutant cybrids was not affected. While this mutation was located in the fourth hydrophobic transmembrane region of ND4 gene, we suggested that mutation of m. 11240C>T might impair the proton pumping channel of complex I but had little effect on the complex I assembly. In conclusion, we identified m. 11240C>T as a novel mitochondrial disease-related mtDNA mutation.
DOI	10.1038/jhg.2016.127
收录类别	SCI
语种	英语
资助项目	Zhejiang Provincial Natural Science foundation of China[LQ15H070005] ; Key Science and Technology Innovation Team of Zhejiang Province[2010R50048] ; Chinese National Science Foundation[81471097] ; Start Foundation of Wenzhou Medical University
WOS研究方向	Genetics & Heredity
WOS类目	Genetics & Heredity
WOS记录号	WOS:000394087600022
出版者	NATURE PUBLISHING GROUP
引用统计	被引频次：12[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.204/handle/2XEOYT63/7127
专题	中国科学院计算技术研究所期刊论文_英文
通讯作者	Fang, Hezhi; Lyu, Jianxin; Yang, Yanling
作者单位	1.Wenzhou Med Univ, Coll Lab Med & Life Sci, Zhejiang Prov Key Lab Med Genet, Key Lab Lab Med,Minist Educ, Wenzhou, Zhejiang, Peoples R China 2.Peking Univ, Dept Pediat, Hosp 1, Beijing, Peoples R China 3.Chinese Acad Sci, Inst Comp Technol, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Xu, Bing,Li, Xiyuan,Du, Miaomiao,et al. Novel mutation of ND4 gene identified by targeted next-generation sequencing in patient with Leigh syndrome[J]. JOURNAL OF HUMAN GENETICS,2017,62(2):291-297.
APA	Xu, Bing.,Li, Xiyuan.,Du, Miaomiao.,Zhou, Chao.,Fang, Hezhi.,...&Yang, Yanling.(2017).Novel mutation of ND4 gene identified by targeted next-generation sequencing in patient with Leigh syndrome.JOURNAL OF HUMAN GENETICS,62(2),291-297.
MLA	Xu, Bing,et al."Novel mutation of ND4 gene identified by targeted next-generation sequencing in patient with Leigh syndrome".JOURNAL OF HUMAN GENETICS 62.2(2017):291-297.