000120074 001__ 120074 000120074 005__ 20240319081013.0 000120074 0247_ $$2doi$$a10.3390/ijms231911002 000120074 0248_ $$2sideral$$a130896 000120074 037__ $$aART-2022-130896 000120074 041__ $$aeng 000120074 100__ $$aJou, C. 000120074 245__ $$aPathological features in paediatric patients with TK2 deficiency 000120074 260__ $$c2022 000120074 5060_ $$aAccess copy available to the general public$$fUnrestricted 000120074 5203_ $$aThymidine 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. 000120074 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B33-20R$$9info:eu-repo/grantAgreement/ES/FIS/PI17-00021$$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI17-00166$$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI20-00340 000120074 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000120074 590__ $$a5.6$$b2022 000120074 592__ $$a1.154$$b2022 000120074 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b66 / 285 = 0.232$$c2022$$dQ1$$eT1 000120074 593__ $$aMedicine (miscellaneous)$$c2022$$dQ1 000120074 591__ $$aCHEMISTRY, MULTIDISCIPLINARY$$b52 / 178 = 0.292$$c2022$$dQ2$$eT1 000120074 593__ $$aPhysical and Theoretical Chemistry$$c2022$$dQ1 000120074 593__ $$aComputer Science Applications$$c2022$$dQ1 000120074 593__ $$aInorganic Chemistry$$c2022$$dQ1 000120074 593__ $$aSpectroscopy$$c2022$$dQ1 000120074 593__ $$aOrganic Chemistry$$c2022$$dQ1 000120074 593__ $$aMolecular Biology$$c2022$$dQ2 000120074 593__ $$aCatalysis$$c2022$$dQ2 000120074 594__ $$a7.8$$b2022 000120074 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000120074 700__ $$aNascimento, A. 000120074 700__ $$aCodina, A. 000120074 700__ $$aMontoya, J. 000120074 700__ $$0(orcid)0000-0002-3217-1424$$aLópez-Gallardo, E.$$uUniversidad de Zaragoza 000120074 700__ $$0(orcid)0000-0001-5964-6138$$aEmperador, S.$$uUniversidad de Zaragoza 000120074 700__ $$0(orcid)0000-0002-0269-7337$$aRuiz-Pesini, E.$$uUniversidad de Zaragoza 000120074 700__ $$aMontero, R. 000120074 700__ $$aNatera-de Benito, D. 000120074 700__ $$aOrtez, C. I. 000120074 700__ $$aMárquez, J. 000120074 700__ $$aZelaya, M. V. 000120074 700__ $$aGutiérrez-Mata, A. 000120074 700__ $$aBadosa, C. 000120074 700__ $$aCarrera-García, L. 000120074 700__ $$aExpósito-Escudero, J. 000120074 700__ $$aRoldán, M. 000120074 700__ $$aCámara, Y. 000120074 700__ $$aMarti, R. 000120074 700__ $$aFerrer, I. 000120074 700__ $$aJiménez-Mallebrera, C. 000120074 700__ $$aArtuch, R. 000120074 7102_ $$11003$$2443$$aUniversidad de Zaragoza$$bDpto. Anatom.Histolog.Humanas$$cArea Histología 000120074 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole. 000120074 773__ $$g23, 19 (2022), 11002[11 pp.]$$pInt. j. mol. sci.$$tInternational Journal of Molecular Sciences$$x1661-6596 000120074 8564_ $$s7632801$$uhttps://zaguan.unizar.es/record/120074/files/texto_completo.pdf$$yVersión publicada 000120074 8564_ $$s2883510$$uhttps://zaguan.unizar.es/record/120074/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000120074 909CO $$ooai:zaguan.unizar.es:120074$$particulos$$pdriver 000120074 951__ $$a2024-03-18-15:20:38 000120074 980__ $$aARTICLE