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Title: Functional consequences of mitochondrial tRNA Trp and tRNA Arg mutations causing combined OXPHOS defects
Authors: Smits, Paulien
Mattijssen, Sandy
Morava, Eva
van den Brand, Mariël
van den Brandt, Frans
Wijburg, Frits
Pruijn, Ger
Smeitink, Jan
Nijtmans, Leo
Rodenburg, Richard
van den Heuvel, Lambertus # ×
Issue Date: Mar-2010
Publisher: Karger
Series Title: European Journal of Human Genetics vol:18 issue:3 pages:324-9
Abstract: Combined oxidative phosphorylation (OXPHOS) system deficiencies are a group of mitochondrial disorders that are associated with a range of clinical phenotypes and genetic defects. They occur in approximately 30% of all OXPHOS disorders and around 4% are combined complex I, III and IV deficiencies. In this study we present two mutations in the mitochondrial tRNA(Trp) (MT-TW) and tRNA(Arg) (MT-TR) genes, m.5556G>A and m.10450A>G, respectively, which were detected in two unrelated patients showing combined OXPHOS complex I, III and IV deficiencies and progressive multisystemic diseases. Both mitochondrial tRNA mutations were almost homoplasmic in fibroblasts and muscle tissue of the two patients and not present in controls. Patient fibroblasts showed a general mitochondrial translation defect. The mutations resulted in lowered steady-state levels and altered conformations of the tRNAs. Cybrid cell lines showed similar tRNA defects and impairment of OXPHOS complex assembly as patient fibroblasts. Our results show that these tRNA(Trp) and tRNA(Arg) mutations cause the combined OXPHOS deficiencies in the patients, adding to the still expanding group of pathogenic mitochondrial tRNA mutations.
ISSN: 1018-4813
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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