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dc.contributor.authorBarbosa Gouveia, Sofía
dc.contributor.authorGonzález Vioque, Emiliano
dc.contributor.authorHermida Ameijeiras, Alvaro 
dc.contributor.authorSuarez, M. U.
dc.contributor.authorMartinez-Gonzalez, M. J.
dc.contributor.authorBorges ., Filipa
dc.contributor.authorWintjes, L.
dc.contributor.authorKappen, A.
dc.contributor.authorRodenburg, R.
dc.contributor.authorCouce Pico, María Luz 
dc.date.accessioned2022-04-29T10:25:43Z
dc.date.available2022-04-29T10:25:43Z
dc.date.issued2020
dc.identifier.issn2073-4425
dc.identifier.otherhttps://www.ncbi.nlm.nih.gov/pubmed/32887222es
dc.identifier.urihttp://hdl.handle.net/20.500.11940/16593
dc.description.abstractThe EARS2 nuclear gene encodes mitochondrial glutamyl-tRNA synthetase, a member of the class I family of aminoacyl-tRNA synthetases (aaRSs) that plays a crucial role in mitochondrial protein biosynthesis by catalyzing the charging of glutamate to mitochondrial tRNA(Glu). Pathogenic EARS2 variants have been associated with a rare mitochondrial disorder known as leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL). The targeted sequencing of 150 nuclear genes encoding respiratory chain complex subunits and proteins implicated in the oxidative phosphorylation (OXPHOS) function was performed. The oxygen consumption rate (OCR), and the extracellular acidification rate (ECAR), were measured. The enzymatic activities of Complexes I-V were analyzed spectrophotometrically. We describe a patient carrying two heterozygous EARS2 variants, c.376C>T (p.Gln126*) and c.670G>A (p.Gly224Ser), with infantile-onset disease and a severe clinical presentation. We demonstrate a clear defect in mitochondrial function in the patient's fibroblasts, suggesting the molecular mechanism underlying the pathogenicity of these EARS2 variants. Experimental validation using patient-derived fibroblasts allowed an accurate characterization of the disease-causing variants, and by comparing our patient's clinical presentation with that of previously reported cases, new clinical and radiological features of LTBL were identified, expanding the clinical spectrum of this disease.en
dc.rightsAtribución 4.0 Internacional
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.meshAdult*
dc.subject.meshBrain Stem*
dc.subject.meshLeukoencephalopathies*
dc.subject.meshRNA*
dc.subject.meshGenetic Variation*
dc.subject.meshPhenotype*
dc.subject.meshGlutamate-tRNA Ligase*
dc.subject.meshAmino Acyl-tRNA Synthetases*
dc.subject.meshMitochondria*
dc.subject.meshHumans*
dc.subject.meshFibroblasts*
dc.subject.meshOxidative Phosphorylation*
dc.subject.meshCells*
dc.subject.meshThalamus*
dc.subject.meshOxygen Consumption*
dc.subject.meshLactic Acid*
dc.titleIdentification of a Novel Variant in EARS2 Associated with a Severe Clinical Phenotype Expands the Clinical Spectrum of LTBLen
dc.typeJournal Articlees
dc.authorsophosBarbosa-Gouveia, S.;Gonzalez-Vioque, E.;Hermida, A.;Suarez, M. U.;Martinez-Gonzalez, M. J.;Borges, F.;Wintjes, L.;Kappen, A.;Rodenburg, R.;Couce, M. L.
dc.identifier.doi10.3390/genes11091028
dc.identifier.pmid32887222
dc.identifier.sophos39511
dc.issue.number9es
dc.journal.titleGENESes
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::EOXI de Santiago de Compostela - Complexo Hospitalario Universitario de Santiago de Compostela::Pediatríaes
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS)es
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::EOXI de Santiago de Compostela - Complexo Hospitalario Universitario de Santiago de Compostela::Neonatoloxíaes
dc.rights.accessRightsopenAccess
dc.subject.decsfenotipo*
dc.subject.decsvariación genética*
dc.subject.decstronco encefálico*
dc.subject.decstálamo*
dc.subject.decsfosforilación oxidativa*
dc.subject.decsconsumo de oxígeno*
dc.subject.decsadulto*
dc.subject.decsleucoencefalopatías*
dc.subject.decsácido láctico*
dc.subject.decsARN*
dc.subject.decsmitocondrias*
dc.subject.decsfibroblastos*
dc.subject.decsaminoacil-ARNt sintetasas*
dc.subject.decshumanos*
dc.subject.decscélulas*
dc.subject.decsglutamato-ARNt ligasa*
dc.subject.keywordCHUSes
dc.subject.keywordIDISes
dc.typefidesArtículo Originales
dc.typesophosArtículo Originales
dc.volume.number11es


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