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Identification and Characterization of New Variants in FOXRED1 Gene Expands the Clinical Spectrum Associated with Mitochondrial Complex I Deficiency
dc.contributor.author | Barbosa-Gouveia, S. | |
dc.contributor.author | González Vioque, Emiliano | |
dc.contributor.author | Borges ., Filipa | |
dc.contributor.author | Gutiérrez-Solana, L. | |
dc.contributor.author | Wintjes, L. | |
dc.contributor.author | Kappen, A. | |
dc.contributor.author | van den Heuvel, L. | |
dc.contributor.author | Leis Trabazo, María Rosaura | |
dc.contributor.author | Rodenburg, R. | |
dc.contributor.author | Couce Pico, María Luz | |
dc.date.accessioned | 2021-09-29T12:43:01Z | |
dc.date.available | 2021-09-29T12:43:01Z | |
dc.date.issued | 2019 | |
dc.identifier.issn | 2077-0383 | |
dc.identifier.other | https://www.ncbi.nlm.nih.gov/pubmed/31434271 | es |
dc.identifier.uri | http://hdl.handle.net/20.500.11940/15375 | |
dc.description.abstract | Complex I (nicotinamide adenine dinucleotide (NADH): ubiquinone oxidoreductase) is the largest complex of the mitochondrial oxidative phosphorylation system (OXPHOS) system. Forty-four subunits encoded in nuclear and mitochondrial genomes compose this multiprotein complex, its assembly being a highly complex process involving at least 15 additional nuclear encoded assembly factors. Complex I deficiency is a mitochondrial disorder usually associated with early-onset severe multisystem disorders characterized by highly variable clinical manifestations. Flavin adenine dinucleotide (FAD)-dependent oxidoreductase domain-containing protein 1 (FOXRED1) is a complex I assembly factor. To date, only five patients with mitochondrial complex I deficiency due to mutations in FOXRED1 have been characterized. Here, we describe a child with ataxia, epilepsy and psychomotor developmental delay carrying two heterozygous FOXRED1 variants, c.920G>A (p.Gly307Glu) and c.733+1G>A. We demonstrate the molecular mechanism supporting the pathogenicity of the FOXRED1 variants, showing a clear deficiency of complex I activity. The reduction in the steady-state level of complex I holoenzyme in patient fibroblasts, confirmed the pathogenicity of the variants and showed the molecular mechanism behind their pathogenicity. A comparison of the clinical presentation of the index case with the previously described cases allowed deepening our knowledge about the clinical variability associated with FOXRED1 defects. | en |
dc.language.iso | eng | |
dc.rights | Atribución 4.0 Internacional | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject.mesh | Epilepsy | * |
dc.title | Identification and Characterization of New Variants in FOXRED1 Gene Expands the Clinical Spectrum Associated with Mitochondrial Complex I Deficiency | es |
dc.type | Artigo | es |
dc.authorsophos | Barbosa-Gouveia, S. | |
dc.authorsophos | González-Vioque, E. | |
dc.authorsophos | Borges, F. | |
dc.authorsophos | Gutiérrez-Solana, L. | |
dc.authorsophos | Wintjes, L. | |
dc.authorsophos | Kappen, A. | |
dc.authorsophos | van den Heuvel, L. | |
dc.authorsophos | Leis, R. | |
dc.authorsophos | Rodenburg, R. | |
dc.authorsophos | Couce, M. L. | |
dc.identifier.doi | 10.3390/jcm8081262 | |
dc.identifier.pmid | 31434271 | |
dc.identifier.sophos | 30576 | |
dc.issue.number | 8 | es |
dc.journal.title | Journal of Clinical Medicine | es |
dc.organization | Servizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::EOXI de Santiago de Compostela - Complexo Hospitalario Universitario de Santiago de Compostela::Pediatría | |
dc.organization | Servizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS) | |
dc.organization | Servizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::EOXI de Santiago de Compostela - Complexo Hospitalario Universitario de Santiago de Compostela::Neonatoloxía | |
dc.page.initial | 1262 | es |
dc.relation.publisherversion | https://res.mdpi.com/d_attachment/jcm/jcm-08-01262/article_deploy/jcm-08-01262.pdf | |
dc.rights.accessRights | openAccess | |
dc.subject.decs | epilepsia | * |
dc.subject.keyword | CHUS | |
dc.subject.keyword | IDIS | |
dc.typefides | Artículo Científico (incluye Original, Original breve, Revisión Sistemática y Meta-análisis) | |
dc.typesophos | Artículo Original | |
dc.volume.number | 8 | es |