title: A novel mutation in the human complex I NDUFS7 subunit associated with Leigh syndrome.
abstract: Defects in NADH:ubiquinone oxidoreductase, the complex I of the mitochondrial respiratory chain represents the most frequent cause of mitochondrial diseases and is associated with a wide clinical spectrum varying from severe lactic acidosis in infants to muscle weakness in adults. Here, we report a patient with Leigh syndrome (LS), born to consanguineous parents, with severe complex I defect and a novel mutation in the NDUFS7 gene subunit. The homozygous mutation at nucleotide (nt) 434 G>A resulted in the modification of the arginine 145 to histidine in a highly conserved region of the protein. Parents were heterozygous carriers for this mutation. The mutation was absent from over than 100 healthy controls from the same ethnic origin. Identifying nuclear mutations as a cause of respiratory chain disorders will enhance the possibility of prenatal diagnosis and help us to understand how moleculardefects can lead to complex I deficiency.
authors.affiliation: INSERM U781, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lebon
authors.forename: Diana
authors.initials: D
authors.lastname: Rodriguez
authors.forename: Delphine
authors.initials: D
authors.lastname: Bridoux
authors.forename: Amal
authors.initials: A
authors.lastname: Zerrad
authors.forename: Agnès
authors.initials: A
authors.lastname: Rötig
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Alain
authors.initials: A
authors.lastname: Legrand
authors.forename: Abdelhamid
authors.initials: A
authors.lastname: Slama
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D005260:Female; D006801:Humans; D007888:Leigh Disease / Q000235:genetics*; D008969:Molecular Sequence Data; D009245:NADH Dehydrogenase / Q000235:genetics* / Q000378:metabolism
chemical_list: D009245:NADH Dehydrogenase; C496410:NDUFS7 protein, human