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

Research output: Contribution to journalArticlepeer-review


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
Issue number1
Publication statusPublished - Jan 1998

ASJC Scopus subject areas

  • Neuroscience(all)


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