An mtDNA mutation, 14453G→A, in the NADH dehydrogenase subunit 6 associated with severe MELAS syndrome

Abstract

We report a novel point mutation in the gene for the mitochondrially encoded ND6 subunit of the NADH:ubiquinone oxidoreductase (complex I of the respiratory chain) in a patient with MELAS syndrome. The mutation causes a change from alanine to valine in the most conserved region of the ND6 subunit. The patient was heteroplasmic for the mutation in both muscle and blood, but the mutation was not detected in the patient's mother. A marked reduction of complex I activity was found in the patient's muscular tissue. This is the first report of a mutation in the ND6 subunit causing MELAS. Our data confirm the genetic heterogeneity in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome, and confirms that MELAS can be caused by mutation in polypeptide-coding mtDNA genes. European Journal of Human Genetics (2001) 9, 805 ± 809.

Mutations in mitochondrially encoded complex I enzyme as the second common cause in a cohort of Chinese patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes

“…[28][29][30][31] In this study, we found T10191C in MTND3, and a large deletion (from 13025-13033/to 14417-14425/) encompassing partial MTND5 and MTND6 in patients 2 and 3, respectively. The T10191C mutation, detected in patient 2 in this study, was first reported in a patient that presented with a progressive Leigh-like clinical picture of epilepsy, strokes, optic atrophy and cognitive decline by Taylor et al 32 Subsequently, several MELAS or LS patients were reported carrying the T10191C mutation.…”

Impaired complex I assembly in a Leigh syndrome patient with a novel missense mutation in the ND6 gene

“…17 This region harbors mutations previously associated with Leigh syndrome 19 and MELAS, 20 and it is a hot-spot for mutations leading to LHON or LHON/dystonia. 4 The LHON primary mutation T14484C causes the same amino acid substitution in the position adjacent to the M63V change.…”

Codon-specific translational defect caused by a wobble modification deficiency in mutant tRNA from a human mitochondrial disease

“…It has been reported that the translational activity of ND6 in cybrid cells is specifically and markedly reduced without a decrease in total mitochondrial protein synthesis when the A3243G or T3271C mtDNA levels are increased (13,14). Furthermore, a point mutation (A14453G) in the structural gene for ND6 was found to be associated with severe MELAS syndrome (47).…”