Cytochrome c oxidase subunit I microdeletion in a patient with motor neuron disease

Annals of Neurology
G P ComiG Scarlato

Abstract

An out-of-frame mutation of the mitochondrial DNA-encoded subunit I of cytochrome c oxidase (COX) was discovered during investigation of a severe isolated muscle COX deficiency in a patient with motor neuron-like degeneration. The mutation is a heteroplasmic 5-bp microdeletion located in the 5' end of the COI gene, leading to premature termination of the corresponding translation product. Western blot analysis, immunohistochemistry, and single-fiber polymerase chain reaction demonstrated a tight correlation between COX defect, COX I expression, and percentage of mutation. COX subunits II, III, and IV were decreased as well, suggesting a defective assembly of COX holoenzyme. The mutation was associated with a clinical phenotype unusual for a mitochondrial disorder, that is, an isolated motor neuron disease (MND) with some atypical findings, including early onset, preferential involvement of the upper motor neuron, and increased cerebrospinal fluid protein content. MND may arise from impaired scavenging and overproduction of free oxygen radicals, a by-product of oxidative phosphorylation (OXPHOS). Our observation suggests that OXPHOS impairment could play a role in the pathogenesis of some MND cases.

References

Jan 1, 1992·Neurology·H J TritschlerN Telerman-Toppet
Jan 1, 1990·Annual Review of Biochemistry·R A Capaldi
Apr 1, 1988·Annals of Neurology·D S GoodinR K Olney
Jul 1, 1996·Journal of the Neurological Sciences·T MitsuiS Saito

❮ Previous
Next ❯

Citations

Oct 29, 2002·Annals of Neurology·Andoni Echaniz-LagunaEliane Lampert
Apr 3, 2007·Journal of Neurology·Catherine PhoenixRobert W Taylor
Feb 26, 2009·Journal of Neurology·Jerry LinSaud A Sadiq
May 24, 2011·Journal of Neurology·Massimiliano FilostoAlessandro Padovani
Nov 16, 2011·Journal of Bioenergetics and Biomembranes·Lee J Martin
Mar 20, 2002·Current Neurology and Neuroscience Reports·C E ShawN Leigh
Jan 1, 2003·Current Neurology and Neuroscience Reports·Serge PrzedborskiLewis P Rowland
Aug 2, 2002·European Journal of Pharmacology·Charles Krieger, Michael R Duchen
Oct 26, 2001·Journal of the Neurological Sciences·G SicilianoL Murri
Sep 17, 2002·Molecular Aspects of Medicine·Vitaliy B Borisov
Jun 17, 2000·Trends in Neurosciences·M F Beal
May 30, 2001·Advanced Drug Delivery Reviews·T Pulkes, M G Hanna
Feb 19, 2002·Neurochemistry International·Fiona M MenziesPamela J Shaw
Dec 14, 1999·Biochimica Et Biophysica Acta·T B ShererJ B Tuttle
Apr 12, 2002·Gene·Antoni BarrientosAlexander Tzagoloff
Jan 28, 2003·Drug Discovery Today·Peter M Mathisen
Jan 11, 2013·Journal of Human Genetics·Martin Patrick HoranJ William O Ballard
Jun 2, 2001·The New England Journal of Medicine·L P Rowland, N A Shneider
Oct 20, 2009·Human Molecular Genetics·Hua YangEric A Schon
Oct 22, 2003·Current Opinion in Rheumatology·Ericka P SimpsonStanley H Appel
Nov 3, 2006·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Rudy G E van EijsdenHubert J M Smeets
Jun 13, 2003·The Neurologist·J Finsterer
Oct 24, 1998·Acta Neurologica Scandinavica·N Delanty, M A Dichter
Apr 24, 1999·BMJ : British Medical Journal·P J Shaw
Jul 19, 2005·Journal of Neurology, Neurosurgery, and Psychiatry·P J Shaw
Mar 13, 2008·Annual Review of Neuroscience·Salvatore DiMauro, Eric A Schon
Aug 16, 2006·Neuro-degenerative Diseases·Luc DupuisJean-Philippe Loeffler
Jan 9, 2009·Human Genomics·Michelangelo MancusoGabriele Siciliano
Dec 19, 2000·Biochemical and Biophysical Research Communications·C ParetG Rödel
May 6, 2014·Revue neurologique·A Chaussenot, V Paquis-Flucklinger
Jun 3, 2008·Brain : a Journal of Neurology·Don MahadDouglas Turnbull
Jan 31, 2013·The Journal of Biological Chemistry·Paula ClementeRafael Garesse
Mar 17, 2009·Journal of Neuropathology and Experimental Neurology·Shoichi SasakiYasuto Itoyama
Mar 16, 2007·Neuropathology and Applied Neurobiology·G SorarùC Angelini
Mar 23, 2007·Acta Neurologica Scandinavica·M Filosto, M Mancuso

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.