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Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency

Nature Genetics volume 11, pages 144–149 (1995)Cite this article

Abstract

We now report a mutation in the nuclear–encoded flavoprotein (Fp) subunit gene of the succinate dehydrogenase (SDH) in two siblings with complex II deficiency presenting as Leigh syndrome. Both patients were homozygous for an Arg554Trp substitution in the Fp subunit. Their parents (first cousins) were heterozygous for the mutation that occurred in a conserved domain of the protein and was absent from 120 controls. The deleterious effect of the Arg to Trp substitution on the catalytic activity of SDH was observed in a SDH− yeast strain transformed with mutant Fp cDNA. The Fp subunit gene is duplicated in the human genome (3q29; 5p15), with only the gene on chromosome 5 expressed in human–hamster somatic cell hybrids. This is the first report of a nuclear gene mutation causing a mitochondrial respiratory chain deficiency in humans.

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Authors and Affiliations

  1. Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-393 et Département de Pédiatrie, Chromosome et Cancer, INSERM U-383, IFREM, Institut Necker, Hôpital des Enfants-Malades, 149, rue de Sèvres, 75743, Paris Cedex, 15, France

    Thomas Bourgeron, Pierre Rustin, Dominique Chretien, Mark Birch-Machin, Marie Bourgeois, Arnold Munnich & Agnès Rötig

  2. Unité de Recherches Génétique, Chromosome et Cancer, INSERM U-383, IFREM, Institut Necker, Hôpital des Enfants-Malades, 149, rue de Sèvres, 75743, Paris Cedex, 15, France

    Evani Viegas-Péquignot

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Bourgeron, T., Rustin, P., Chretien, D. et al. Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency. Nat Genet 11, 144–149 (1995). https://doi.org/10.1038/ng1095-144

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