A constant and similar assembly defect of mitochondrial respiratory chain complex I allows rapid identification of NDUFS4 mutations in patients with Leigh syndrome.
Biochim Biophys Acta
; 1822(6): 1062-9, 2012 Jun.
Article
em En
| MEDLINE
| ID: mdl-22326555
ABSTRACT
Isolated complex I deficiency is a frequent cause of respiratory chain defects in childhood. In this study, we report our systematic approach with blue native PAGE (BN-PAGE) to study mitochondrial respiratory chain assembly in skin fibroblasts from patients with Leigh syndrome and CI deficiency. We describe five new NDUFS4 patients with a similar and constant abnormal BN-PAGE profile and present a meta-analysis of the literature. All NDUFS4 mutations that have been tested with BN-PAGE result in a constant and similar abnormal assembly profile with a complete loss of the fully assembled complex I usually due to a truncated protein and the loss of its canonical cAMP dependent protein kinase phosphorylation consensus site. We also report the association of abnormal brain MRI images with this characteristic BN-PAGE profile as the hallmarks of NDUFS4 mutations and the first founder NDUFS4 mutations in the North-African population.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença de Leigh
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Doenças Mitocondriais
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Complexo I de Transporte de Elétrons
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NADH Desidrogenase
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
/
Systematic_reviews
Limite:
Female
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Humans
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Infant
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Male
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article