000150760 001__ 150760
000150760 005__ 20251017144650.0
000150760 0247_ $$2doi$$a10.1038/ejhg.2015.112
000150760 0248_ $$2sideral$$a93622
000150760 037__ $$aART-2016-93622
000150760 041__ $$aeng
000150760 100__ $$aAsencio, C.
000150760 245__ $$aSevere encephalopathy associated to pyruvate dehydrogenase mutations and unbalanced coenzyme Q 10 content
000150760 260__ $$c2016
000150760 5060_ $$aAccess copy available to the general public$$fUnrestricted
000150760 5203_ $$aCoenzyme Q 10 (CoQ 10) deficiency is associated to a variety of clinical phenotypes including neuromuscular and nephrotic disorders. We report two unrelated boys presenting encephalopathy, ataxia, and lactic acidosis, who died with necrotic lesions in different areas of brain. Levels of CoQ 10 and complex II+III activity were increased in both skeletal muscle and fibroblasts, but it was a consequence of higher mitochondria mass measured as citrate synthase. In fibroblasts, oxygen consumption was also increased, whereas steady state ATP levels were decreased. Antioxidant enzymes such as NQO1 and MnSOD and mitochondrial marker VDAC were overexpressed. Mitochondria recycling markers Fis1 and mitofusin, and mtDNA regulatory Tfam were reduced. Exome sequencing showed mutations in PDHA1 in the first patient and in PDHB in the second. These genes encode subunits of pyruvate dehydrogenase complex (PDH) that could explain the compensatory increase of CoQ 10 and a defect of mitochondrial homeostasis. These two cases describe, for the first time, a mitochondrial disease caused by PDH defects associated with unbalanced of both CoQ 10 content and mitochondria homeostasis, which severely affects the brain. Both CoQ 10 and mitochondria homeostasis appears as new markers for PDH associated mitochondrial disorders.
000150760 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
000150760 590__ $$a4.287$$b2016
000150760 591__ $$aGENETICS & HEREDITY$$b35 / 165 = 0.212$$c2016$$dQ1$$eT1
000150760 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b71 / 286 = 0.248$$c2016$$dQ1$$eT1
000150760 592__ $$a2.092$$b2016
000150760 593__ $$aGenetics (clinical)$$c2016$$dQ1
000150760 593__ $$aGenetics$$c2016$$dQ1
000150760 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000150760 700__ $$aRodríguez-Hernandez, M. A.
000150760 700__ $$aBriones, P.
000150760 700__ $$0(orcid)0000-0003-1770-6299$$aMontoya, J.$$uUniversidad de Zaragoza
000150760 700__ $$aCortés, A.
000150760 700__ $$0(orcid)0000-0001-5964-6138$$aEmperador, S.
000150760 700__ $$aGavil''n, A.
000150760 700__ $$0(orcid)0000-0002-0269-7337$$aRuiz-Pesini, E.$$uUniversidad de Zaragoza
000150760 700__ $$aYubero, D.
000150760 700__ $$aMontero, R.
000150760 700__ $$aPineda, M.
000150760 700__ $$aO''Callaghan, M. M.
000150760 700__ $$aAlcázar-Fabra, M.
000150760 700__ $$aSalviati, L.
000150760 700__ $$aArtuch, R.
000150760 700__ $$aNavas, P.
000150760 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000150760 773__ $$g24, 3 (2016), 367-372$$pEur. j. hum. genet.$$tEuropean Journal of Human Genetics$$x1018-4813
000150760 8564_ $$s1274872$$uhttps://zaguan.unizar.es/record/150760/files/texto_completo.pdf$$yPostprint
000150760 8564_ $$s3036653$$uhttps://zaguan.unizar.es/record/150760/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000150760 909CO $$ooai:zaguan.unizar.es:150760$$particulos$$pdriver
000150760 951__ $$a2025-10-17-14:36:03
000150760 980__ $$aARTICLE