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

TitleCytochrome c oxidase subunit I microdeletion in a patient with motor neuron disease.
Publication TypeJournal Article
Year of Publication1998
AuthorsComi, 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
JournalAnn Neurol
Date Published1998 Jan
KeywordsAdult, Base Sequence, Brain, DNA, Mitochondrial, Electron Transport Complex IV, Gene Deletion, Histocytochemistry, Humans, Immunohistochemistry, Isoenzymes, Magnetic Resonance Imaging, Male, Molecular Sequence Data, Motor Neuron Disease, Muscles, Nucleic Acid Heteroduplexes, Polymerase Chain Reaction

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.

Alternate JournalAnn. Neurol.
Citation Key10.1002/ana.410430119
PubMed ID9450776
Grant List767 / / Telethon / Italy