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Previous Volume 351:2080-2086 November 11, 2004 Number 20 Next

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SUMMARY

Although most components of the mitochondrial translation apparatus are encoded by nuclear genes, all known molecular defects associated with impaired mitochondrial translation are due to mutations in mitochondrial DNA. We investigated two siblings with a severe defect in mitochondrial translation, reduced levels of oxidative phosphorylation complexes containing mitochondrial DNA (mtDNA)–encoded subunits, and progressive hepatoencephalopathy. We mapped the defective gene to a region on chromosome 3q containing elongation factor G1 (EFG1), which encodes a mitochondrial translation factor. Sequencing of EFG1 revealed a mutation affecting a conserved residue of the guanosine triphosphate (GTP)–binding domain. These results define a new class of gene defects underlying disorders of oxidative phosphorylation.

Source Information

From the Nijmegen Center for Mitochondrial Disorders (M.J.H.C., C.U., J.G.A.M.A.H., F.J.M.F.T., L.P.H., J.A.M.S.) at the Departments of Pediatrics (M.J.H.C., C.U., F.J.M.F.T., L.P.H., J.A.M.S.) and Human Genetics (J.G.A.M.A.H.), Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands; Montreal Neurological Institute and the Department of Human Genetics, McGill University, Montreal (H.A., F.S., E.A.S.); the Department of Pediatrics, Klinikum Neukölln, Berlin (R.R.); and Brunel Institute of Cancer Genetics and Pharmacogenomics, Faculty of Life Sciences, Brunel University, Uxbridge, United Kingdom (R.F.N.).

Drs. Coenen and Antonicka contributed equally to this article.

Address reprint requests to Dr. Smeitink at Nijmegen Center for Mitochondrial Disorders, Department of Pediatrics, University Medical Center Nijmegen, 6500 HB Nijmegen, the Netherlands, or at j.smeitink{at}cukz.umcn.nl.

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