A constant and similar assembly defect of mitochondrial respiratory chain complex I allows rapid identification of NDUFS4 mutations in patients with Leigh syndrome

作者：Assouline Z; Jambou M; Rio M; Bole Feysot C; de Lonlay P; Barnerias C; Desguerre I; Bonnemains C; Guillermet C; Steffann J; Munnich A; Bonnefont J P; Roetig A; Lebre A S^*

来源：Biochimica et Biophysica Acta-Molecular Basis of Disease, 2012, 1822(6): 1062-1069.

DOI：10.1016/j.bbadis.2012.01.013

• Mitochondrial disorder
• Respiratory chain complex I assembly
• BN-PAGE
• NDUFS4 gene
• Leigh syndrome
• Founder mutation

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 Cl deficiency. We describe five new wNDUFS4 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.

• 出版日期2012-6