title: Mutant mitochondrial elongation factor G1 and combined oxidative phosphorylation deficiency.
abstract: 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.
authors.affiliation: Nijmegen Center for Mitochondrial Disorders, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Marieke J H
authors.initials: MJ
authors.lastname: Coenen
authors.forename: Hana
authors.initials: H
authors.lastname: Antonicka
authors.forename: Cristina
authors.initials: C
authors.lastname: Ugalde
authors.forename: Florin
authors.initials: F
authors.lastname: Sasarman
authors.forename: Rainer
authors.initials: R
authors.lastname: Rossi
authors.forename: J G A M Angelien
authors.initials: JG
authors.lastname: Heister
authors.forename: Robert F
authors.initials: RF
authors.lastname: Newbold
authors.forename: Frans J M F
authors.initials: FJ
authors.lastname: Trijbels
authors.forename: Lambert P
authors.initials: LP
authors.lastname: van den Heuvel
authors.forename: Eric A
authors.initials: EA
authors.lastname: Shoubridge
authors.forename: Jan A M
authors.initials: JA
authors.lastname: Smeitink
mesh_terms: D002893:Chromosomes, Human, Pair 3; D018076:DNA, Complementary / Q000032:analysis; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D017093:Liver Failure / Q000235:genetics*; D008297:Male; D008831:Microcephaly / Q000235:genetics; D028361:Mitochondrial Diseases / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation; D020653:Peptide Elongation Factor G / Q000235:genetics*; D014176:Protein Biosynthesis; D017422:Sequence Analysis, DNA
chemical_list: D018076:DNA, Complementary; D004272:DNA, Mitochondrial; D045222:Electron Transport Chain Complex Proteins; C441680:GFM1 protein, human; D024101:Mitochondrial Proteins; D020653:Peptide Elongation Factor G; D006160:Guanosine Triphosphate