Baculovirus Complementation Restores a Novel NDUFAF2 Mutation Causing Complex I Deficiency

被引：40

作者：

Hoefs, Saskia J. G. ^{[1
]}

Dieteren, Cindy E. J. ^{[1
,2
]}

Rodenburg, Richard J. ^{[1
]}

Naess, Karin ^{[3
]}

Bruhn, Helene ^{[4
]}

Wibom, Rolf ^{[4
]}

Wagena, Esther ^{[1
]}

Willems, Peter H. ^{[2
]}

Smeitink, Jan A. M. ^{[1
]}

Nijtmans, Leo G. ^{[1
]}

van den Heuvel, Lambert P. ^{[1
]}

机构：

[1] Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mitochondrial Disorders, Dept Pediat, NL-6500 HB Nijmegen, Netherlands

[2] Radboud Univ Nijmegen, Med Ctr, Dept Biochem, Nijmegen Ctr Mol Life Sci, NL-6500 HB Nijmegen, Netherlands

[3] Karolinska Inst, Dept Clin Sci, Div Pediat, Stockholm, Sweden

[4] Karolinska Inst, Dept Lab Med, Stockholm, Sweden

来源：

HUMAN MUTATION | 2009年 / 30卷 / 07期

关键词：

Leigh Syndrome; mitochondria; OXPHOS system; complex I deficiency; NDUFAF2; B172L; MITOCHONDRIAL COMPLEX; UBIQUINONE OXIDOREDUCTASE; LEIGH-SYNDROME; NDUFS4; GENE; DISEASE; SUBUNITS; NADH; DNA; IDENTIFICATION; PATHOLOGY;

D O I：

10.1002/humu.21037

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Mitochondrial complex I deficiency is the most common defect of the OXPHOS system. We report a patient from consanguineous parents with a complex I deficiency expressed in skin fibroblasts. Homozygosity mapping revealed several homozygous regions with candidate genes, including the gene encoding an assembly factor for complex I, NDUFAF2. Screening of this gene on genomic DNA revealed a homozygous stop-codon resulting in a truncation of the protein at position 38. The mutation causes a severely reduced activity and a disturbed assembly of complex I. A baculovirus containing the GFP-tagged wild-type NDUFAF2 gene was used to prove the functional consequences of the mutation. The expression and activity of complex I was almost completely rescued by complementation of the patient fibroblasts with the baculovirus. Therefore, the homozygous substitution in NDUFAF2 is the disease-causing mutation, which results in a complex I deficiency in the fibroblasts of the patient. (C) 2009 Wiley-Liss, Inc.

引用

页码：E728 / E736

页数：9

共 31 条

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