title: A mitochondrial cytochrome b mutation but no mutations of nuclearly encoded subunits in ubiquinol cytochrome c reductase (complex III) deficiency.
abstract: Ubiquinol cytochrome c reductase (complex III) deficiency represents a clinically heterogeneous group of mitochondrial respiratory chain disorders that can theoretically be subject to either a nuclear or a mitochondrial mode of inheritance. In an attempt to elucidate the molecular bases of the disease, we first determined the nucleotide sequence of three unknown subunits (9.5 kDa, 7.2 kDa, 6.4 kDa) by cyberscreening of human expressed sequence tag data bases and sequenced the 11 cDNA subunits encoding complex III in five patients with isolated complex III deficiency. No mutation in the nuclearly encoded complex III subunits was observed, but a mutation in the cd2 helix of the mitochondrial (mt) cytochrome b gene was found to alter the conformation of the bc1 complex in one patient with severe hypertrophic cardiomyopathy. The present study is highly relevant to genetic counseling as the absence of mtDNA mutations in all but one patient in our series strongly supports autosomal rather than maternal inheritance in the majority of patients with complex III deficiency.
authors.affiliation: Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U393, Hôpital des Enfants-Malades, Paris, France.
authors.forename: I
authors.initials: I
authors.lastname: Valnot
authors.forename: J
authors.initials: J
authors.lastname: Kassis
authors.forename: D
authors.initials: D
authors.lastname: Chretien
authors.forename: P
authors.initials: P
authors.lastname: de Lonlay
authors.forename: B
authors.initials: B
authors.lastname: Parfait
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: J
authors.initials: J
authors.lastname: Kachaner
authors.forename: P
authors.initials: P
authors.lastname: Rustin
authors.forename: A
authors.initials: A
authors.lastname: Rötig
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002467:Cell Nucleus / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003573:Cytochrome b Group / Q000235:genetics*; D018076:DNA, Complementary / Q000032:analysis; D002658:Developmental Disabilities / Q000235:genetics; D014450:Electron Transport Complex III / Q000172:deficiency* / Q000235:genetics*; D020224:Expressed Sequence Tags; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D007231:Infant, Newborn; D007700:Kinetics; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D008969:Molecular Sequence Data; D009132:Muscles / Q000201:enzymology; D009154:Mutation; D011110:Polymorphism, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D003573:Cytochrome b Group; D018076:DNA, Complementary; D014450:Electron Transport Complex III