120074 20240319081013.0 doi 10.3390/ijms231911002 sideral 130896 ART-2022-130896 eng Jou, C. Pathological features in paediatric patients with TK2 deficiency 2022 Access copy available to the general public Unrestricted Thymidine kinase (TK2) deficiency causes mitochondrial DNA depletion syndrome. We aimed to report the clinical, biochemical, genetic, histopathological, and ultrastructural features of a cohort of paediatric patients with TK2 deficiency. Mitochondrial DNA was isolated from muscle biopsies to assess depletions and deletions. The TK2 genes were sequenced using Sanger sequencing from genomic DNA. All muscle biopsies presented ragged red fibres (RRFs), and the prevalence was greater in younger ages, along with an increase in succinate dehydrogenase (SDH) activity and cytochrome c oxidase (COX)-negative fibres. An endomysial inflammatory infiltrate was observed in younger patients and was accompanied by an overexpression of major histocompatibility complex type I (MHC I). The immunofluorescence study for complex I and IV showed a greater number of fibres than those that were visualized by COX staining. In the ultrastructural analysis, we found three major types of mitochondrial alterations, consisting of concentrically arranged lamellar cristae, electrodense granules, and intramitochondrial vacuoles. The pathological features in the muscle showed substantial differences in the youngest patients when compared with those that had a later onset of the disease. Additional ultrastructural features are described in the muscle biopsy, such as sarcomeric de-structuration in the youngest patients with a more severe phenotype. info:eu-repo/grantAgreement/ES/DGA/B33-20R info:eu-repo/grantAgreement/ES/FIS/PI17-00021 info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI17-00166 info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI20-00340 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 5.6 2022 BIOCHEMISTRY & MOLECULAR BIOLOGY 66 / 285 = 0.232 2022 Q1 T1 CHEMISTRY, MULTIDISCIPLINARY 52 / 178 = 0.292 2022 Q2 T1 1.154 2022 Medicine (miscellaneous) 2022 Q1 Physical and Theoretical Chemistry 2022 Q1 Computer Science Applications 2022 Q1 Inorganic Chemistry 2022 Q1 Spectroscopy 2022 Q1 Organic Chemistry 2022 Q1 Molecular Biology 2022 Q2 Catalysis 2022 Q2 7.8 2022 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Nascimento, A. Codina, A. Montoya, J. López-Gallardo, E. Universidad de Zaragoza (orcid)0000-0002-3217-1424 Emperador, S. Universidad de Zaragoza (orcid)0000-0001-5964-6138 Ruiz-Pesini, E. Universidad de Zaragoza (orcid)0000-0002-0269-7337 Montero, R. Natera-de Benito, D. Ortez, C. I. Márquez, J. Zelaya, M. V. Gutiérrez-Mata, A. Badosa, C. Carrera-García, L. Expósito-Escudero, J. Roldán, M. Cámara, Y. Marti, R. Ferrer, I. Jiménez-Mallebrera, C. Artuch, R. 1003 443 Universidad de Zaragoza Dpto. Anatom.Histolog.Humanas Area Histología 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 23, 19 (2022), 11002[11 pp.] Int. j. mol. sci. International Journal of Molecular Sciences 1661-6596 7632801 http://zaguan.unizar.es/record/120074/files/texto_completo.pdf Versión publicada 2883510 http://zaguan.unizar.es/record/120074/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:120074 articulos driver 2024-03-18-15:20:38 ARTICLE