Xu 2017 J Hum Genet
|Xu B, Li X, Du M, Zhou C, Fang H, Lyu J, Yang Y (2017) Novel mutation of ND4 gene identified by targeted next-generation sequencing in patient with Leigh syndrome. J Hum Genet 62:291-7.|
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.
Labels: MiParea: Respiration, mtDNA;mt-genetics, Patients Pathology: Neurodegenerative
Organism: Human Tissue;cell: Blood cells, Platelet Preparation: Intact cells Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase
Coupling state: LEAK, ROUTINE