Progressive cavitating leukoencephalopathy associated with respiratory chain complex i deficiency and a novel mutation in NDUFS1

Mariana Ferreira, Alessandra Torraco, Teresa Rizza, Fabiana Fattori, Maria Chiara Meschini, Cinzia Castana, Nancy E. Go, Frank E. Nargang, Margarida Duarte, Fiorella Piemonte, Carlo Dionisi-Vici, Arnaldo Videira, Laura Vilarinho, Filippo M. Santorelli, Rosalba Carrozzo, Enrico Bertini

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)9-17
Number of pages9
JournalNeurogenetics
Volume12
Issue number1
DOIs
Publication statusPublished - Feb 2011

Keywords

  • Complex I
  • Lactic acidosis
  • NDUFS1
  • Progressive cavitating leukoencephalopathy

ASJC Scopus subject areas

  • Genetics(clinical)
  • Cellular and Molecular Neuroscience
  • Genetics

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