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

Giacomo P. Comi, Andreina Bordoni, Sabrina Salani, Liliana Franceschina, Monica Sciacco, Alessandro Prelle, Francesco Fortunato, Massimo Zeviani, Laura Napoli, Nereo Bresolin, Maurizio Moggio, Carlo D. Ausenda, Jan Willem Taanman, Guglielmo Scarlato

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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.

Original languageEnglish
Pages (from-to)110-116
Number of pages7
JournalAnnals of Neurology
Volume43
Issue number1
DOIs
Publication statusPublished - Jan 1998

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Motor Neuron Disease
Electron Transport Complex IV
Oxidoreductases
Oxidative Phosphorylation
Motor Neurons
Mutation
Cerebrospinal Fluid Proteins
Mitochondrial Diseases
Nerve Degeneration
Holoenzymes
Frameshift Mutation
Mitochondrial DNA
Free Radicals
Reactive Oxygen Species
Western Blotting
Immunohistochemistry
Observation
Phenotype
Muscles
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Cytochrome c oxidase subunit I microdeletion in a patient with motor neuron disease. / Comi, Giacomo P.; Bordoni, Andreina; Salani, Sabrina; Franceschina, Liliana; Sciacco, Monica; Prelle, Alessandro; Fortunato, Francesco; Zeviani, Massimo; Napoli, Laura; Bresolin, Nereo; Moggio, Maurizio; Ausenda, Carlo D.; Taanman, Jan Willem; Scarlato, Guglielmo.

In: Annals of Neurology, Vol. 43, No. 1, 01.1998, p. 110-116.

Research output: Contribution to journalArticle

Comi, GP, Bordoni, A, Salani, S, Franceschina, L, Sciacco, M, Prelle, A, Fortunato, F, Zeviani, M, Napoli, L, Bresolin, N, Moggio, M, Ausenda, CD, Taanman, JW & Scarlato, G 1998, 'Cytochrome c oxidase subunit I microdeletion in a patient with motor neuron disease', Annals of Neurology, vol. 43, no. 1, pp. 110-116. https://doi.org/10.1002/ana.410430119
Comi, Giacomo P. ; Bordoni, Andreina ; Salani, Sabrina ; Franceschina, Liliana ; Sciacco, Monica ; Prelle, Alessandro ; Fortunato, Francesco ; Zeviani, Massimo ; Napoli, Laura ; Bresolin, Nereo ; Moggio, Maurizio ; Ausenda, Carlo D. ; Taanman, Jan Willem ; Scarlato, Guglielmo. / Cytochrome c oxidase subunit I microdeletion in a patient with motor neuron disease. In: Annals of Neurology. 1998 ; Vol. 43, No. 1. pp. 110-116.
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