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 trans-membrane 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.
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Acknowledgements
This work was supported by the Zhejiang Provincial Natural Science foundation of China (LQ15H070005), Key Science and Technology Innovation Team of Zhejiang Province (2010R50048), Chinese National Science Foundation (81471097) and the Start Foundation of Wenzhou Medical University (to Hezhi Fang).
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Xu, B., Li, X., Du, M. et al. Novel mutation of ND4 gene identified by targeted next-generation sequencing in patient with Leigh syndrome. J Hum Genet 62, 291–297 (2017). https://doi.org/10.1038/jhg.2016.127
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DOI: https://doi.org/10.1038/jhg.2016.127
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