NDUFA2 复合物 I 突变导致 Leigh 病。
NDUFA2 complex I mutation leads to Leigh disease.
作者信息
Hoefs Saskia J G, Dieteren Cindy E J, Distelmaier Felix, Janssen Rolf J R J, Epplen Andrea, Swarts Herman G P, Forkink Marleen, Rodenburg Richard J, Nijtmans Leo G, Willems Peter H, Smeitink Jan A M, van den Heuvel Lambert P
机构信息
Department of Pediatrics, Nijmegen Center for Mitochondrial Disorders, Radboud University Nijmegen Medical Center, Nijmegen 6500 HB, The Netherlands.
出版信息
Am J Hum Genet. 2008 Jun;82(6):1306-15. doi: 10.1016/j.ajhg.2008.05.007.
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.
线粒体分离的复合物I缺乏是最常见的氧化磷酸化缺陷。我们报告了一名患者，其皮肤成纤维细胞和肌肉组织中均存在分离的复合物I缺乏。由于父母是近亲，我们进行了纯合性定位以鉴定包含候选基因（如5号染色体上的NDUFA2）的纯合区域。在基因组DNA上对该基因进行筛选发现了一个干扰正确剪接并导致外显子2跳跃的突变。在外显子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有关。用表达NDUFA2基因的杆状病毒系统（部分）挽救了复合物I的表达、活性和去极化。
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