Combined enzymatic complex I and III deficiency associated with mutations in the nuclear encoded NDUFS4 gene
| Autor: | S. M. S. Budde, C.A.F. Buskens, R. Van Coster, Martina Baethmann, L.P.W.J. van den Heuvel, Antoon J.M. Janssen, L. DeMeirleir, J. M. F. Trijbels, Jan A.M. Smeitink, R.J.P. Smeets, Thomas Voit |
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| Rok vydání: | 2000 |
| Předmět: |
Male
Nuclear gene Genotype Nonsense mutation DNA Mutational Analysis Biophysics Biology medicine.disease_cause Biochemistry Oxidative Phosphorylation Consanguinity Electron Transport Complex III medicine Humans Point Mutation NADH NADPH Oxidoreductases Thymidine phosphorylase Muscle Skeletal Molecular Biology Gene Cells Cultured DNA Primers Genetics Cell Nucleus Mutation Electron Transport Complex I Transition (genetics) Base Sequence NDUFS4 Infant Een diermodel voor mitochondrieel ademhalingsketen complex I deficiëntie Cell Biology Fibroblasts Molecular biology Stop codon Mitochondria Codon Terminator Female Genes Lethal Leigh Disease Polymorphism Restriction Fragment Length An animal model for complex I deficiency of the mitochondrial respiratory chain |
| Zdroj: | Biochemical and Biophysical Research Communications, 275, 63-68 Biochemical and Biophysical Research Communications, 275, pp. 63-68 |
| ISSN: | 0006-291X |
| Popis: | Combined OXPHOS-system enzyme deficiencies are observed in approximately 25% of all OXPHOS-system disturbances. Of these, combined complex I and III deficiency is relatively scarce. So far, only mtDNA and thymidine phosphorylase (TP) mutations have been associated with combined OXPHOS-system disturbances. In this report we show, for the first time, that a nuclear gene mutation in a structural, nuclear encoded complex I gene is associated with combined complex I and III deficiency. After our initial report we describe mutations in the NDUFS4 gene of complex I in two additional patients. The first mutation is a deletion of G at position 289 or 290. Amino acid 96 changes from a tryptophan to a stop codon. The mutation was found homozygous in the patient; both parents are heterozygous for the mutation. The second mutation is a transition from C to T at cDNA position 316. Codon is changed from CGA (arginine) to TGA (stop). The patient is homozygous for the mutation; both parents are heterozygous. Both mutations in the NDUFS4 gene led to a premature stop in Leigh-like patients with an early lethal phenotype. We hypothesise that the structural integrity of the OXPHOS system, in mammal supermolecular structures, may be responsible for the observed biochemical features. |
| Databáze: | OpenAIRE |
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