title: Mutations of the SCO1 gene in mitochondrial cytochrome c oxidase deficiency with neonatal-onset hepatic failure and encephalopathy.
abstract: Cytochrome c oxidase (COX) catalyzes both electron transfer from cytochrome c to molecular oxygen and the concomitant vectorial proton pumping across the inner mitochondrial membrane. Studying a large family with multiple cases of neonatal ketoacidotic comas and isolated COX deficiency, we have mapped the disease locus to chromosome 17p13.1, in a region encompassing two candidate genes involved in COX assembly-namely, SCO1 and COX10. Mutation screening revealed compound heterozygosity for SCO1 gene mutations in the patients. The mutated allele, inherited from the father, harbored a 2-bp frameshift deletion (DeltaGA; nt 363-364) resulting in both a premature stop codon and a highly unstable mRNA. The maternally inherited mutation (C520T) changed a highly conserved proline into a leucine in the protein (P174L). This proline, adjacent to the CxxxC copper-binding domain of SCO1, is likely to play a crucial role in the tridimentional structure of the domain. Interestingly, the clinical presentation of SCO1-deficient patients markedly differs from that of patients harboring mutations in other COX assembly and/or maturation genes.
authors.affiliation: Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-393, Hôpital Necker-Enfants Malades, 75743 Paris, France.
authors.forename: I
authors.initials: I
authors.lastname: Valnot
authors.forename: S
authors.initials: S
authors.lastname: Osmond
authors.forename: N
authors.initials: N
authors.lastname: Gigarel
authors.forename: B
authors.initials: B
authors.lastname: Mehaye
authors.forename: J
authors.initials: J
authors.lastname: Amiel
authors.forename: V
authors.initials: V
authors.lastname: Cormier-Daire
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: J P
authors.initials: JP
authors.lastname: Bonnefont
authors.forename: P
authors.initials: P
authors.lastname: Rustin
authors.forename: A
authors.initials: A
authors.lastname: Rötig
mesh_terms: D017668:Age of Onset; D000595:Amino Acid Sequence; D001483:Base Sequence; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D030401:Cytochrome-c Oxidase Deficiency; D004252:DNA Mutational Analysis; D004579:Electron Transport; D003576:Electron Transport Complex IV / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D017093:Liver Failure / Q000150:complications* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D008297:Male; D008661:Metabolism, Inborn Errors / Q000150:complications* / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009132:Muscles / Q000201:enzymology / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D016415:Sequence Alignment
chemical_list: D003576:Electron Transport Complex IV