Title | Novel mutation of ND4 gene identified by targeted next-generation sequencing in patient with Leigh syndrome |
Authors | Xu, Bing Li, Xiyuan Du, Miaomiao Zhou, Chao Fang, Hezhi Lyu, Jianxin Yang, Yanling |
Affiliation | 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. Peking Univ, Dept Pediat, Hosp 1, Beijing, Peoples R China. Chinese Acad Sci, Inst Comp Technol, Beijing, Peoples R China. Wenzhou Med Univ, Dept Lab Med, Coll Lab Med & Life Sci, 502 Tongde Bldg, Wenzhou 325035, Peoples R China. Yang, YL (reprint author), Peking Univ, Hosp 1, Beijing 100034, Peoples R China. |
Keywords | HEREDITARY OPTIC NEUROPATHY COMPLEX-I MITOCHONDRIAL-DNA HUMAN-CELLS DISEASE IMPAIRMENT FAMILY |
Issue Date | 2017 |
Publisher | JOURNAL OF HUMAN GENETICS |
Citation | JOURNAL OF HUMAN GENETICS.2017,62(2),291-297. |
Abstract | 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. |
URI | http://hdl.handle.net/20.500.11897/457346 |
ISSN | 1434-5161 |
DOI | 10.1038/jhg.2016.127 |
Indexed | SCI(E) PubMed |
Appears in Collections: | 第一医院 |