caa a22 4500 445364475 CHVBK 20180317142925.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s10048-010-0265-2 doi (NATIONALLICENCE)springer-10.1007/s10048-010-0265-2 Progressive cavitating leukoencephalopathy associated with respiratory chain complex I deficiency and a novel mutation in NDUFS1 [Elektronische Daten] [Mariana Ferreira, Alessandra Torraco, Teresa Rizza, Fabiana Fattori, Maria Meschini, Cinzia Castana, Nancy Go, Frank Nargang, Margarida Duarte, Fiorella Piemonte, Carlo Dionisi-Vici, Arnaldo Videira, Laura Vilarinho, Filippo Santorelli, Rosalba Carrozzo, Enrico Bertini] We present clinical, neuroimaging, and molecular data on the identification of a new homozygous c.1783A>G (p.Thr595Ala) mutation in NDUFS1 in two inbred siblings with isolated complex I deficiency associated to a progressive cavitating leukoencephalopathy, a clinical and neuroradiological entity originally related to unknown defects of the mitochondrial energy metabolism. In both sibs, the muscle biopsy showed severe reduction of complex I enzyme activity, which was not obvious in fibroblasts. We also observed complex I dysfunction in a Neurospora crassa model of the disease, obtained by insertional mutagenesis, and in patient fibroblasts grown in galactose. Altogether, these results indicate that the NDUFS1 mutation is responsible for the disease and complex I deficiency. Clinical presentation of complex I defect is heterogeneous and includes an ample array of clinical phenotypes. Expanding the number of allelic variants in NDUFS1, our findings also contribute to a better understanding on the function of complex I. Springer-Verlag, 2010 Progressive cavitating leukoencephalopathy nationallicence Lactic acidosis nationallicence Complex I nationallicence NDUFS1 nationallicence Ferreira Mariana Centro de Genética Médica Jacinto Magalhães, Instituto Nacional de Saúde Ricardo Jorge, Porto, Portugal aut Torraco Alessandra Unit of Molecular Medicine, Bambino Gesù Children's Hospital, Rome, Italy aut Rizza Teresa Unit of Molecular Medicine, Bambino Gesù Children's Hospital, Rome, Italy aut Fattori Fabiana Unit of Molecular Medicine, Bambino Gesù Children's Hospital, Rome, Italy aut Meschini Maria Unit of Molecular Medicine, Bambino Gesù Children's Hospital, Rome, Italy aut Castana Cinzia Metabolic Unit, II Pediatric Division, Ospedale G. Di Cristina, Palermo, Italy aut Go Nancy Department of Biological Sciences, University of Alberta, T6G 2E9, Edmont, AB, Canada aut Nargang Frank Department of Biological Sciences, University of Alberta, T6G 2E9, Edmont, AB, Canada aut Duarte Margarida IBMC—Instituto de Biologia Molecular e Celular, Porto, Portugal aut Piemonte Fiorella Unit of Molecular Medicine, Bambino Gesù Children's Hospital, Rome, Italy aut Dionisi-Vici Carlo Division of Metabolism, Bambino Gesù Children's Hospital, Rome, Italy aut Videira Arnaldo ICBAS Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, Portugal aut Vilarinho Laura Centro de Genética Médica Jacinto Magalhães, Instituto Nacional de Saúde Ricardo Jorge, Porto, Portugal aut Santorelli Filippo UOC Neurogenetica e Malattie Neuromuscolari, IRCCS Fondazione Stella Maris, Pisa, Italy aut Carrozzo Rosalba Unit of Molecular Medicine, Bambino Gesù Children's Hospital, Rome, Italy aut Bertini Enrico Unit of Molecular Medicine, Bambino Gesù Children's Hospital, Rome, Italy aut neurogenetics Springer-Verlag 12/1(2011-02-01), 9-17 1364-6745 12:1<9 2011 12 10048 https://doi.org/10.1007/s10048-010-0265-2 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10048-010-0265-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ferreira Mariana Centro de Genética Médica Jacinto Magalhães, Instituto Nacional de Saúde Ricardo Jorge, Porto, Portugal aut NATIONALLICENCE 700 1- Torraco Alessandra Unit of Molecular Medicine, Bambino Gesù Children's Hospital, Rome, Italy aut NATIONALLICENCE 700 1- Rizza Teresa Unit of Molecular Medicine, Bambino Gesù Children's Hospital, Rome, Italy aut NATIONALLICENCE 700 1- Fattori Fabiana Unit of Molecular Medicine, Bambino Gesù Children's Hospital, Rome, Italy aut NATIONALLICENCE 700 1- Meschini Maria Unit of Molecular Medicine, Bambino Gesù Children's Hospital, Rome, Italy aut NATIONALLICENCE 700 1- Castana Cinzia Metabolic Unit, II Pediatric Division, Ospedale G. Di Cristina, Palermo, Italy aut NATIONALLICENCE 700 1- Go Nancy Department of Biological Sciences, University of Alberta, T6G 2E9, Edmont, AB, Canada aut NATIONALLICENCE 700 1- Nargang Frank Department of Biological Sciences, University of Alberta, T6G 2E9, Edmont, AB, Canada aut NATIONALLICENCE 700 1- Duarte Margarida IBMC—Instituto de Biologia Molecular e Celular, Porto, Portugal aut NATIONALLICENCE 700 1- Piemonte Fiorella Unit of Molecular Medicine, Bambino Gesù Children's Hospital, Rome, Italy aut NATIONALLICENCE 700 1- Dionisi-Vici Carlo Division of Metabolism, Bambino Gesù Children's Hospital, Rome, Italy aut NATIONALLICENCE 700 1- Videira Arnaldo ICBAS Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Porto, Portugal aut NATIONALLICENCE 700 1- Vilarinho Laura Centro de Genética Médica Jacinto Magalhães, Instituto Nacional de Saúde Ricardo Jorge, Porto, Portugal aut NATIONALLICENCE 700 1- Santorelli Filippo UOC Neurogenetica e Malattie Neuromuscolari, IRCCS Fondazione Stella Maris, Pisa, Italy aut NATIONALLICENCE 700 1- Carrozzo Rosalba Unit of Molecular Medicine, Bambino Gesù Children's Hospital, Rome, Italy aut NATIONALLICENCE 700 1- Bertini Enrico Unit of Molecular Medicine, Bambino Gesù Children's Hospital, Rome, Italy aut NATIONALLICENCE 773 0- neurogenetics Springer-Verlag 12/1(2011-02-01), 9-17 1364-6745 12:1<9 2011 12 10048 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer