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

被引：40

作者：

Assouline, Z. ^{[2
,3
]}

Jambou, M. ^{[2
,3
]}

Rio, M. ^{[2
,3
]}

Bole-Feysot, C. ^{[6
]}

de Lonlay, P. ^{[2
,3
]}

Barnerias, C. ^{[2
,3
]}

Desguerre, I. ^{[2
,3
]}

Bonnemains, C. ^{[4
]}

Guillermet, C. ^{[5
]}

Steffann, J. ^{[2
,3
]}

Munnich, A. ^{[2
,3
]}

Bonnefont, J. P. ^{[2
,3
]}

Roetig, A. ^{[2
]}

Lebre, A. S. ^{[1
,2
,3
]}

机构：

[1] Hop Necker Enfants Malad, Dept Genet, INSERM, U781, F-75015 Paris, France

[2] Univ Paris 05, Paris, France

[3] Hop Necker Enfants Malad, AP HP, Serv Genet Malad Metabol & Neurol Pediat, F-75743 Paris 15, France

[4] CHU Brabois Enfant, INSERM, U954, Ctr Reference Malad Hereditaires Metab, F-54500 Vandoeuvre Les Nancy, France

[5] Hop St Jacques, CHU Besancon, Serv Pediat 2, F-25030 Besancon, France

[6] Hop Necker Enfants Malad, Fdn Imagine, F-75015 Paris, France

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2012年 / 1822卷 / 06期

关键词：

Mitochondrial disorder; Respiratory chain complex I assembly; BN-PAGE; NDUFS4; gene; Leigh syndrome; Founder mutation; NONSENSE MUTATION; AQDQ SUBUNIT; DEFICIENCY; GENE; PROTEIN; ELECTROPHORESIS; DYSFUNCTIONS; PATTERN;

D O I：

10.1016/j.bbadis.2012.01.013

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2012 Elsevier B.V. All rights reserved.

引用

页码：1062 / 1069

页数：8

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