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
| Autor: | R.H. Triepels, Jan A.M. Smeitink, Jan Loeffen, L.P.W.J. van den Heuvel, J. M. F. Trijbels, R.J.P. Smeets |
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| Rok vydání: | 2000 |
| Předmět: |
Mitochondrial DNA
Enzyme complex Moleculair genetisch onderzoek van mitochondriopathieën DNA Complementary Molecular Sequence Data Mutation Missense Cohort Studies Mitochondrial myopathy Gene Frequency Mitochondrial Encephalomyopathies Complementary DNA Genetics medicine Humans NADH NADPH Oxidoreductases Amino Acid Sequence Gene Genetics (clinical) Polymorphism Single-Stranded Conformational Netherlands Cell Nucleus Molecular genetic studies of mitochondriocytopathies biology Base Sequence NADH dehydrogenase Infant Newborn Sequence Analysis DNA medicine.disease Molecular biology Mitochondrial respiratory chain NDUFB7 Child Preschool biology.protein Cell Adhesion Molecules |
| Zdroj: | Human Genetics, 106, 385-391 Human Genetics, 106, 4, pp. 385-391 |
| ISSN: | 0340-6717 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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