title: Leigh syndrome associated with mitochondrial complex I deficiency due to a novel mutation in the NDUFS1 gene.
abstract: BACKGROUND
  Mutations in the nuclear-encoded subunits of complex I of the mitochondrial respiratory chain are a recognized cause of Leigh syndrome (LS). Recently, 6 mutations in the NDUFS1 gene were identified in 3 families.
  
  
  OBJECTIVE
  To describe a Spanish family with LS, complex I deficiency in muscle, and a novel mutation in the NDUFS1 gene.
  
  
  METHODS
  Using molecular genetic approaches, we identified the underlying molecular defect in a patient with LS with a complex I defect.
  
  
  METHODS
  The proband was a child who displayed the clinical features of LS.
  
  
  RESULTS
  Muscle biochemistry results showed a complex I defect of the mitochondrial respiratory chain. Sequencing analysis of the mitochondrial DNA-encoded ND genes, the nuclear DNA-encoded NDUFV1, NDUFS1, NDUFS2, NDUFS4, NDUFS6, NDUFS7, NDUFS8, and NDUFAB1 genes, and the complex I assembly factor CIA30 gene revealed a novel homozygous L231V mutation (c.691C-->G) in the NDUFS1 gene. The parents were heterozygous carriers of the L231V mutation.
  
  
  CONCLUSIONS
  Identifying nuclear mutations as a cause of respiratory chain disorders will enhance the possibility of prenatal diagnosis and help us understand how molecular defects can lead to complex I deficiency.
authors.affiliation: Centro de Investigación, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Martín
authors.forename: Alberto
authors.initials: A
authors.lastname: Blázquez
authors.forename: Luis G
authors.initials: LG
authors.lastname: Gutierrez-Solana
authors.forename: Daniel
authors.initials: D
authors.lastname: Fernández-Moreira
authors.forename: Paz
authors.initials: P
authors.lastname: Briones
authors.forename: Antoni L
authors.initials: AL
authors.lastname: Andreu
authors.forename: Rafael
authors.initials: R
authors.lastname: Garesse
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Campos
authors.forename: Joaquín
authors.initials: J
authors.lastname: Arenas
mesh_terms: D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D042967:Electron Transport Complex I / Q000172:deficiency* / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007888:Leigh Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D009245:NADH Dehydrogenase; D013030:Spain
chemical_list: D004272:DNA, Mitochondrial; C487793:NDUFS1 protein, human; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I