NDUFA2 complex I mutation leads to Leigh disease

被引：98

作者：

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

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

Distelmaier, Felix ^{[1
,2
,3
]}

Janssen, Rolf J. R. J. ^{[1
]}

Epplen, Andrea ^{[4
]}

Swarts, Herman G. P. ^{[2
]}

Forkink, Marleen ^{[1
]}

Rodenburg, Richard J. ^{[1
]}

Nijtmans, Leo G. ^{[1
]}

Willems, Peter H. ^{[2
]}

Smeitink, Jan A. M. ^{[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, Nijmegen Ctr Mol Life Sci, Dept Membrane Biochem, NL-6500 HB Nijmegen, Netherlands

[3] Univ Dusseldorf, Dept Gen Pediat, D-40225 Dusseldorf, Germany

[4] Ruhr Univ Bochum, Dept Human Genet, D-44801 Bochum, Germany

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2008年 / 82卷 / 06期

关键词：

D O I：

10.1016/j.ajhg.2008.05.007

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Mitochondrial isolated complex I deficiency is the most frequently encountered OXPHOS defect. We report a patient with an isolated complex I deficiency expressed in skin fibroblasts as well as muscle tissue. Because the parents were consanguineous, we performed homozygosity mapping to identify homozygous regions containing candidate genes such as NDUFA2 on chromosome 5. Screening of this gene on genomic DNA revealed a mutation that interferes with correct splicing and results in the skipping of exon 2. Exon skipping was confirmed on the mRNA level. The mutation in this accessory subunit causes reduced activity and disturbed assembly of complex I. Furthermore, the mutation is associated with a mitochondrial depolarization. The expression and activity of complex I and the depolarization was (partially) rescued with a baculovirus system expressing the NDUFA2 gene.

引用

页码：1306 / 1315

页数：10

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