Ramiro Martinez

VHIR Vall d’Hebron Research Institute, Barcino, Catalonia, Spain

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Publications (2)7.62 Total impact

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    ABSTRACT: Mutations in the ATP6 gene are reported to be associated with Leber hereditary optic neuropathy, bilateral striatal necrosis, coronary atherosclerosis risk and neuropathy, ataxia and retinitis pigmentosa/maternally inherited Leigh syndromes. Here, we present a patient with neuropathy, ataxia and retinitis pigmentosa syndrome, in whom a previously undescribed mutation was detected in the ATP6 gene: m.8839G>C. Several observations support the concept that m.8839G>C is pathogenically involved in the clinical phenotype of this patient: 1) the mutation was heteroplasmic in muscle; 2) mutation load was higher in the symptomatic patient than in the asymptomatic carriers; 3) cybrids carrying this mutation presented lower cell proliferation, increased mtDNA copy number, increased steady-state OxPhos protein levels, and decreased mitochondrial membrane potential with respect to isogenic wild-type cybrids; 4) this change was not observed in 2959 human mtDNAs from different mitochondrial haplogroups; 5) the affected amino acid was conserved in all the ATP6 sequences analyzed; and 6) using in silico prediction, the mutation was classified as "probably damaging". However, measurement of ATP synthesis showed no differences between wild-type and mutated cybrids. Thus, we suggest that m.8839G>C may lower the efficiency between proton translocation within F0 and F1 rotation, required for ATP synthesis. Further experiments are needed to fully characterize the molecular mechanisms involved in m.8839G>C pathogenicity.
    Genes Brain and Behavior 10/2013; · 3.60 Impact Factor
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    ABSTRACT: Mitochondrial DNA (mtDNA) content is important for understanding many cellular processes. Several pre-analytical factors, from sample collection to DNA extraction can affect measurement of mtDNA copy number. In the present study, whole blood samples yielded a higher mtDNA copy number than buffy coat samples. mtDNA content is affected by the cell separation method used and the time between blood withdrawal and cell separation. Thus, reference values must be established with the same type of sample. As to the DNA isolation and purification method, the manual phenol method can give randomly false high values. The QIAamp DNA Mini Kit provided the most highly reproducible mtDNA/nDNA yield.
    Mitochondrion 04/2009; 9(4):242-6. · 4.03 Impact Factor