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 language | English |
|---|---|
| Pages (from-to) | 110-116 |
| Number of pages | 7 |
| Journal | Annals of Neurology |
| Volume | 43 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 1998 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Cytochrome c oxidase subunit I microdeletion in a patient with motor neuron disease
AU - Comi, Giacomo P.
AU - Bordoni, Andreina
AU - Salani, Sabrina
AU - Franceschina, Liliana
AU - Sciacco, Monica
AU - Prelle, Alessandro
AU - Fortunato, Francesco
AU - Zeviani, Massimo
AU - Napoli, Laura
AU - Bresolin, Nereo
AU - Moggio, Maurizio
AU - Ausenda, Carlo D.
AU - Taanman, Jan Willem
AU - Scarlato, Guglielmo
PY - 1998/1
Y1 - 1998/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0031915174&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031915174&partnerID=8YFLogxK
U2 - 10.1002/ana.410430119
DO - 10.1002/ana.410430119
M3 - Article
C2 - 9450776
AN - SCOPUS:0031915174
VL - 43
SP - 110
EP - 116
JO - Annals of Neurology
JF - Annals of Neurology
SN - 0364-5134
IS - 1
ER -