Several of the MRP genes map to loci associated with disorders consistent with impaired oxidative phosphorylation, such as Leigh Syndrome, multiple mitochondrial dysfunctions, and non-syndromic hearing loss.
Bilateral striatal necrosis caused by ADAR mutations in two siblings with dystonia and freckles-like skin changes that should be differentiated from Leigh syndrome.
Furthermore, FRG mice backcrossed to the NOD background and repopulated with huHeps and human red blood cells supported reproducible transition from LS infection to blood-stage infection.
In the present study we show that the function of the F1F0-ATPase is impaired in lymphocytes from ten individuals harbouring the mtDNA T8993G point mutation associated with NARP (neuropathy, ataxia and retinitis pigmentosa) and Leigh syndrome.
A 5-year-old child with clinical and radiologic evidence of Leigh syndrome (LS) showed a T-->C mutation at position nt 8993 in the mitochondrial DNA (instead of the more common T-->G substitution), resulting in an amino acid change from a highly conserved leucine to proline in subunit 6 of mitochondrial ATPase.
A mitochondrial ATPase 6 mutation is associated with Leigh syndrome in a family and affects proton flow and adenosine triphosphate output when modeled in Escherichia coli.
We sequenced the encoded complex I units: ND2, ND3, ND4, ND5 and ND6 genes and the mitochondrial ATPase 6, tRNA(Val), tRNA(Leu(UUR)), tRNA(Trp) and tRNA(Lys) genes in 10 unrelated patients with Leigh syndrome.
The MT-ATP6 m.9185T>C p.Leu220Pro mutation, previously associated with Leigh syndrome, was present in all family members, while the MT-TL1 m.3271T>C mutation, a known cause of MELAS syndrome, was observed in the sole patient with MELAS presentation.
A T-to-C missense mutation at nucleotide position 9,185 in the protein-coding ATP6 gene of the mitochondrial genome was present at high heteroplasmy in members of a Canadian family with Leigh syndrome with predominant ataxia and peripheral neuropathy.
Cytoplasmic transfer of the mtDNA nt 8993 T-->G (ATP6) point mutation associated with Leigh syndrome into mtDNA-less cells demonstrates cosegregation with a decrease in state III respiration and ADP/O ratio.
The rare T8993C mutation in the MT-ATP6 gene is generally considered to be clinically milder, but there is marked clinical heterogeneity ranging from asymptomatic carriers to fatal infantile Leigh syndrome.