NDUFA2 complex I mutation leads to Leigh disease
NDUFA2 complex I mutation leads to Leigh disease
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DOI：
10.1016/j.ajhg.2008.05.007
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发表时间：
2008-06-01
影响因子：
9.8
通讯作者：
van den Heuvel, Lambert P.
中科院分区：
文献类型：
--
作者：
Hoefs, Saskia J. G.;Dieteren, Cindy E. J.;van den Heuvel, Lambert P.
线粒体孤立复合物I缺陷是最常见的OXPHOS缺陷。我们报告了一个病人与孤立的复合物I缺乏症表达在皮肤成纤维细胞以及肌肉组织。由于父母是近亲，我们进行了纯合性定位，以确定纯合区域包含候选基因，如5号染色体上的NDUFA 2。在基因组DNA上筛选该基因揭示了干扰正确剪接并导致外显子2跳跃的突变。在mRNA水平上证实了外显子跳跃。该辅助亚基中的突变导致复合物I的活性降低和组装紊乱。此外，该突变与线粒体去极化相关。用表达NDUFA2基因的杆状病毒系统（部分）拯救复合物I和去极化的表达和活性。
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.