title: Characterization of the human complex I NDUFB7 and 17.2-kDa cDNAs and mutational analysis of 19 genes of the HP fraction in complex I-deficient-patients.
abstract: Deficiency of NADH:ubiquinone oxidoreductase, the first enzyme complex of the mitochondrial respiratory chain, is one of the most frequent causes of human mitochondrial encephalomyopathies. A relatively small percentage of human complex I deficiency is associated with mitochondrial DNA mutations. cDNA characterization and mutational analysis of the structural complex I genes in 19 complex I-deficient patients, in whom common mtDNA mutations have been excluded, has so far revealed five patients with alterations in evolutionary conserved nuclear-encoded proteins. In order to complete our knowledge about the expected 36 structural nuclear complex I genes, we characterized the NDUFB7 and the 17.2-kDa cDNA sequences of the hydrophobic (HP) fraction of the complex. Subsequently, we screened all subunits of this fraction for the presence of mutations in those 14 patients of our initial patient cohort in whom the underlying genetic cause had not been elucidated. Strikingly, no pathogenic mutations were found in the HP subunits that would explain the complex I deficiency in our patients. Other strategies are needed to unravel proteins involved in the pathogenesis of the complicated cellular network of transcription until correct assemblage of complex I.
authors.affiliation: Nijmegen Center for Mitochondrial Disorders, Department of Pediatrics, University Medical Center Nijmegen, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Triepels
authors.forename: J
authors.initials: J
authors.lastname: Smeitink
authors.forename: J
authors.initials: J
authors.lastname: Loeffen
authors.forename: R
authors.initials: R
authors.lastname: Smeets
authors.forename: F
authors.initials: F
authors.lastname: Trijbels
authors.forename: L
authors.initials: L
authors.lastname: van den Heuvel
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D015815:Cell Adhesion Molecules; D002467:Cell Nucleus / Q000235:genetics*; D002675:Child, Preschool; D015331:Cohort Studies; D018076:DNA, Complementary / Q000235:genetics*; D005787:Gene Frequency; D006801:Humans; D007231:Infant, Newborn; D017237:Mitochondrial Encephalomyopathies / Q000453:epidemiology / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009247:NADH, NADPH Oxidoreductases / Q000172:deficiency / Q000235:genetics*; D009426:Netherlands / Q000453:epidemiology; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA
chemical_list: D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; C409164:NDUFB7 protein, human; D009247:NADH, NADPH Oxidoreductases