title: A deletion in the human QP-C gene causes a complex III deficiency resulting in hypoglycaemia and lactic acidosis.
abstract: Mitochondrial respiratory chain complex III (ubiquinol-cytochrome c reductase) consists of 11 subunits, only one (cytochrome b) being encoded by the mitochondrial DNA. Disorders of complex III are comparatively rare but are nevertheless present as a clinically heterogeneous group of diseases. To date, no mutation in any of the nuclear-encoded subunits has been described. We report here a deletion in the nuclear gene UQCRB encoding the human ubiquinone-binding protein of complex III (QP-C subunit or subunit VII) in a consanguineous family with an isolated complex III defect. In the proband, a homozygous 4-bp deletion was identified at nucleotides 338-341 of the cDNA predicting both a change in the last seven amino acids and an addition of a stretch of 14 amino acids at the C-terminal end of the protein. Both parents were found to be heterozygous for the deletion, which was absent from 55 controls. Low temperature (-196 degrees C) spectral studies performed on isolated mitochondria from cultured skin fibroblast of the proband showed a decreased cytochrome b content suggestive of a role for the QP-C subunit in the assembly or maintenance of complex III structure.
authors.affiliation: Laboratoire de Biochimie 1, AP-HP Hôpital de Bicêtre, 78 Rue du Général Leclerc, Cédex, 94275 Le Kremlin Bicetre, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Haut
authors.forename: Michèle
authors.initials: M
authors.lastname: Brivet
authors.forename: Guy
authors.initials: G
authors.lastname: Touati
authors.forename: Pierre
authors.initials: P
authors.lastname: Rustin
authors.forename: Sophie
authors.initials: S
authors.lastname: Lebon
authors.forename: Angela
authors.initials: A
authors.lastname: Garcia-Cazorla
authors.forename: Jean Marie
authors.initials: JM
authors.lastname: Saudubray
authors.forename: Audrey
authors.initials: A
authors.lastname: Boutron
authors.forename: Alain
authors.initials: A
authors.lastname: Legrand
authors.forename: Abdelhamid
authors.initials: A
authors.lastname: Slama
mesh_terms: D000140:Acidosis, Lactic / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000235:genetics*; D003080:Cold Temperature; D003573:Cytochrome b Group / Q000032:analysis; D014450:Electron Transport Complex III / Q000172:deficiency*; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D017353:Gene Deletion; D022781:Hepatocytes / Q000201:enzymology; D006801:Humans; D007003:Hypoglycemia / Q000235:genetics* / Q000378:metabolism; D007223:Infant; D008214:Lymphocytes / Q000201:enzymology; D008928:Mitochondria / Q000201:enzymology; D008969:Molecular Sequence Data; D012867:Skin / Q000473:pathology
chemical_list: D002352:Carrier Proteins; D003573:Cytochrome b Group; C027208:ubiquinone-binding proteins; D014450:Electron Transport Complex III