Cytochrome c oxidase deficiency associated with the first stop-codon point mutation in human mtDNA

American Journal of Human Genetics
M G HannaN W Wood

Abstract

We have identified the first stop-codon point mutation in mtDNA to be reported in association with human disease. A 36-year-old woman experienced episodes of encephalopathy accompanied by lactic acidemia and had exercise intolerance and proximal myopathy. Histochemical analysis showed that 90% of muscle fibers exhibited decreased or absent cytochrome c oxidase (COX) activity. Biochemical studies confirmed a severe isolated reduction in COX activity. Muscle immunocytochemistry revealed a pattern suggestive of a primary mtDNA defect in the COX-deficient fibers and was consistent with either reduced stability or impaired assembly of the holoenzyme. Sequence analysis of mtDNA identified a novel heteroplasmic G-->A point mutation at position 9952 in the patient's skeletal muscle, which was not detected in her leukocyte mtDNA or in that of 120 healthy controls or 60 additional patients with mitochondrial disease. This point mutation is located in the 3' end of the gene for subunit III of COX and is predicted to result in the loss of the last 13 amino acids of the highly conserved C-terminal region of this subunit. It was not detected in mtDNA extracted from leukocytes, skeletal muscle, or myoblasts of the patient's mother or her two ...Continue Reading

References

Apr 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·W M BrownA C Wilson
Dec 1, 1977·Brain : a Journal of Neurology·J A Morgan-HughesJ B Clark
Apr 1, 1992·Brain : a Journal of Neurology·V M MannC D Marsden
Oct 25, 1989·Nucleic Acids Research·I NelsonP Lestienne
Oct 1, 1986·Brain : a Journal of Neurology·R K PettyJ A Morgan-Hughes
Nov 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·R E GilesD C Wallace
Apr 9, 1981·Nature·S AndersonI G Young
Sep 1, 1995·Neuromuscular Disorders : NMD·G ManfrediS DiMauro
Jul 15, 1994·Genomics·M Tanaka, T Ozawa
Dec 19, 1995·Biochemistry·S WuH Rottenberg
Jul 1, 1997·Nature Genetics·K M ClarkD M Turnbull

❮ Previous
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Citations

Jan 2, 2003·Annals of Neurology·Danae LiolitsaMichael G Hanna
Sep 1, 2005·Journal of Biomedical Science·Wei-Wen KuoChih-Yang Huang
Jan 6, 2000·Journal of the Neurological Sciences·N HowellL A Bindoff
Sep 17, 2002·Molecular Aspects of Medicine·Vitaliy B Borisov
May 30, 2001·Advanced Drug Delivery Reviews·T Pulkes, M G Hanna
Apr 12, 2002·Gene·Antoni BarrientosAlexander Tzagoloff
Aug 27, 2005·Mitochondrion·M Pilar Bayona-BafaluyJosé A Enríquez
Jan 11, 2013·Journal of Human Genetics·Martin Patrick HoranJ William O Ballard
Mar 13, 2003·European Journal of Biochemistry·Melyssa BrattonBrigitte Meunier
Sep 30, 1999·The New England Journal of Medicine·A L AndreuS DiMauro
Mar 6, 2008·BMC Genomics·Rute R da FonsecaAgostinho Antunes
Dec 19, 2000·Biochemical and Biophysical Research Communications·C ParetG Rödel
Jul 31, 2012·Free Radical Biology & Medicine·Satish Srinivasan, Narayan G Avadhani
May 29, 2012·Journal of the Neurological Sciences·Rami MassieMargherita Milone
Dec 18, 2010·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Rosetta MarottaSteven J Collins
Jun 24, 2008·Journal of the Neurological Sciences·Josef Finsterer
Nov 10, 2011·The Mount Sinai Journal of Medicine, New York·Anthony H V Schapira
Sep 16, 1999·American Journal of Human Genetics·S RahmanA H Schapira
Nov 4, 2008·Biochimica Et Biophysica Acta·Lucia ValenteValeria Tiranti
Jun 12, 2013·Cell Reports·Robert D S PitceathlyUNKNOWN UK10K Consortium
Aug 18, 2009·Biochimica Et Biophysica Acta·Francisca Diaz
Dec 12, 2001·Seminars in Cell & Developmental Biology·S DiMauro
Jun 21, 2011·Parkinson's Disease·Anthony H V Schapira, Matthew Gegg
Oct 2, 2001·American Journal of Medical Genetics·E A Shoubridge
Nov 11, 2006·Medicine and Science in Sports and Exercise·Tuomo RankinenClaude Bouchard
May 16, 2007·Muscle & Nerve·Lee-Jun C Wong
Sep 9, 2004·Medicine and Science in Sports and Exercise·Tuomo RankinenClaude Bouchard
Aug 6, 2003·Medicine and Science in Sports and Exercise·Louis PérusseClaude Bouchard
Apr 23, 2020·Molecular & Cellular Proteomics : MCP·Daniella H HockDavid A Stroud

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