The First Nuclear-Encoded Complex I Mutation in a Patient wit Leigh Syndrome
| Autor: | Renier Mullaart, Markus Schuelke, Lambert P. van den Heuvel, R.J.H. Smeets, Ralf H. Triepels, Frans J.M. Trijbels, Rob C.A. Sengers, Jan A.M. Smeitink, Ben C.J. Hamel, Jan Loeffen |
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| Rok vydání: | 1998 |
| Předmět: |
Male
Moleculair genetisch onderzoek van mitochondriopathieën Enzyme complex Heterozygote NDUFS8 DNA Mutational Analysis Molecular Sequence Data Restriction Mapping Respiratory chain Gene Expression Biology Compound heterozygosity Complementary DNA Consensus Sequence Complex I medicine Genetics Humans NADH NADPH Oxidoreductases Genetics(clinical) Amino Acid Sequence RNA Messenger Leigh disease Genetics (clinical) Cells Cultured Cell Nucleus Molecular genetic studies of mitochondriocytopathies Electron Transport Complex I Base Sequence Leigh NDUFS2 Infant Newborn Onderzoek van mitochondrieel DNA in het kader van diagnostiek van mitochondriële myopathieen Fibroblasts medicine.disease Analysis of mitochondrial DNA as part of the diagnosis of mitochondrial myopathies Mitochondria Mutation Mitochondriocytopathies Ferredoxins Female Leigh Disease Research Article |
| Zdroj: | American Journal of Human Genetics, 63, pp. 1598-1608 American Journal of Human Genetics, 63, 1598-1608 |
| ISSN: | 0002-9297 |
| Popis: | SummaryNicotinamide adenine dinucleotide (NADH):ubiquinone oxidoreductase (complex I) is the largest multiprotein enzyme complex of the respiratory chain. The nuclear-encoded NDUFS8 (TYKY) subunit of complex I is highly conserved among eukaryotes and prokaryotes and contains two 4Fe4S ferredoxin consensus patterns, which have long been thought to provide the binding site for the iron-sulfur cluster N-2. The NDUFS8 cDNA contains an open reading frame of 633 bp, coding for 210 amino acids. Cycle sequencing of amplified NDUFS8 cDNA of 20 patients with isolated enzymatic complex I deficiency revealed two compound heterozygous transitions in a patient with neuropathologically proven Leigh syndrome. The first mutation was a C236T (P79L), and the second mutation was a G305A (R102H). Both mutations were absent in 70 control alleles and cosegregated within the family. A progressive clinical phenotype proceeding to death in the first months of life was expressed in the patient. In the 19 other patients with enzymatic complex I deficiency, no mutations were found in the NDUFS8 cDNA. This article describes the first molecular genetic link between a nuclear-encoded subunit of complex I and Leigh syndrome. |
| Databáze: | OpenAIRE |
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