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- Title
A mutant mitochondrial respiratory chain assembly protein causes complex III deficiency in patients with tubulopathy, encephalopathy and liver failure.
- Authors
de Lonlay, P; Valnot, I; Barrientos, A; Gorbatyuk, M; Tzagoloff, A; Taanman, J W; Benayoun, E; Chrétien, D; Kadhom, N; Lombès, A; de Baulny, H O; Niaudet, P; Munnich, A; Rustin, P; Rötig, A
- Abstract
Complex III (CIII; ubiquinol cytochrome c reductase of the mitochondrial respiratory chain) catalyzes electron transfer from succinate and nicotinamide adenine dinucleotide-linked dehydrogenases to cytochrome c. CIII is made up of 11 subunits, of which all but one (cytochrome b) are encoded by nuclear DNA. CIII deficiencies are rare and manifest heterogeneous clinical presentations. Although pathogenic mutations in the gene encoding mitochondrial cytochrome b have been described, mutations in the nuclear-DNA-encoded subunits have not been reported. Involvement of various genes has been indicated in assembly of yeast CIII (refs. 8-11). So far only one such gene, BCS1L, has been identified in human. BCS1L represents, therefore, an obvious candidate gene in CIII deficiency. Here, we report BCS1L mutations in six patients, from four unrelated families and presenting neonatal proximal tubulopathy, hepatic involvement and encephalopathy. Complementation study in yeast confirmed the deleterious effect of these mutations. Mutation of BCS1L would seem to be a frequent cause of CIII deficiency, as one-third of our patients have BCS1L mutations.
- Publication
Nature genetics, 2001, Vol 29, Issue 1, p57
- ISSN
1061-4036
- Publication type
Journal Article
- DOI
10.1038/ng706