المؤلفون: Hannah, Hayhurst, Irenaeus F M, de Coo, Dorota, Piekutowska-Abramczuk, Charlotte L, Alston, Sunil, Sharma, Kyle, Thompson, Rocio, Rius, Langping, He, Sila, Hopton, Rafal, Ploski, Elzbieta, Ciara, Nicole J, Lake, Alison G, Compton, Martin B, Delatycki, Aad, Verrips, Penelope E, Bonnen, Simon A, Jones, Andrew A, Morris, David, Shakespeare, John, Christodoulou, Dorota, Wesol-Kucharska, Dariusz, Rokicki, Hubert J M, Smeets, Ewa, Pronicka, David R, Thorburn, Grainne S, Gorman, Robert, McFarland, Robert W, Taylor, Yi Shiau, Ng

المصدر: Annals of Clinical and Translational Neurology

مصطلحات موضوعية: Hydroxymethyl and Formyl Transferases, Male, Mitochondrial Diseases, Adolescent, Biopsy, Infant, Newborn, Infant, Fibroblasts, Prognosis, Mitochondria, Cohort Studies, Mitochondrial Proteins, Child, Preschool, Genomic Structural Variation, Mutation, Humans, Female, Leigh Disease, Erratum, Child, Retrospective Studies

الوصف: Mitochondrial methionyl-tRNA formyltransferase (MTFMT) is required for the initiation of translation and elongation of mitochondrial protein synthesisRetrospective cohort study combining new cases and previously published cases.Thirty-eight patients with pathogenic variants inPatients that harbour pathogenic variants in

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::2cc9b423544ca3b4a32ed517a409765aTest
https://pubmed.ncbi.nlm.nih.gov/31020008Test

المؤلفون: Syeda T, Ahmed, Charlotte L, Alston, Sila, Hopton, Langping, He, Iain P, Hargreaves, Gavin, Falkous, Monika, Oláhová, Robert, McFarland, Doug M, Turnbull, Mariana C, Rocha, Robert W, Taylor

المصدر: Scientific Reports

مصطلحات موضوعية: Cell Nucleus, Male, Electron Transport Complex I, Mitochondrial Diseases, Biopsy, Fluoroimmunoassay, Fluorescent Antibody Technique, NADH Dehydrogenase, DNA, Mitochondrial, Oxidative Phosphorylation, Article, Mitochondria, Genetic Heterogeneity, Child, Preschool, Mutation, Humans, Female, Child, Muscle, Skeletal

الوصف: Isolated Complex I (CI) deficiency is the most commonly observed mitochondrial respiratory chain biochemical defect, affecting the largest OXPHOS component. CI is genetically heterogeneous; pathogenic variants affect one of 38 nuclear-encoded subunits, 7 mitochondrial DNA (mtDNA)-encoded subunits or 14 known CI assembly factors. The laboratory diagnosis relies on the spectrophotometric assay of enzyme activity in mitochondrially-enriched tissue homogenates, requiring at least 50 mg skeletal muscle, as there is no reliable histochemical method for assessing CI activity directly in tissue cryosections. We have assessed a validated quadruple immunofluorescent OXPHOS (IHC) assay to detect CI deficiency in the diagnostic setting, using 10 µm transverse muscle sections from 25 patients with genetically-proven pathogenic CI variants. We observed loss of NDUFB8 immunoreactivity in all patients with mutations affecting nuclear-encoding structural subunits and assembly factors, whilst only 3 of the 10 patients with mutations affecting mtDNA-encoded structural subunits showed loss of NDUFB8, confirmed by BN-PAGE analysis of CI assembly and IHC using an alternative, commercially-available CI (NDUFS3) antibody. The IHC assay has clear diagnostic potential to identify patients with a CI defect of Mendelian origins, whilst highlighting the necessity of complete mitochondrial genome sequencing in the diagnostic work-up of patients with suspected mitochondrial disease.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::0c05f692b046b2586c3c841300f2608bTest
https://pubmed.ncbi.nlm.nih.gov/29142257Test