NDUFA10 突变导致 Leigh 病患者复合体 I 缺陷。
NDUFA10 mutations cause complex I deficiency in a patient with Leigh disease.
机构信息
Department of Paediatrics, Nijmegen Centre for Mitochondrial Disorders, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
出版信息
Eur J Hum Genet. 2011 Mar;19(3):270-4. doi: 10.1038/ejhg.2010.204. Epub 2010 Dec 8.
Abstract
Mitochondrial complex I deficiency is the most common defect of the oxidative phosphorylation system. We report a patient with Leigh syndrome who showed a complex I deficiency expressed in cultured fibroblasts and muscle tissue. To find the genetic cause of the complex I deficiency, we screened the mitochondrial DNA and the nuclear-encoded subunits of complex I. We identified compound-heterozygous mutations in the NDUFA10 gene, encoding an accessory subunit of complex I. The first mutation disrupted the start codon and the second mutation resulted in an amino acid substitution. The fibroblasts of the patient displayed decreased amount and activity, and a disturbed assembly of complex I. These results indicate that NDUFA10 is a novel candidate gene to screen for disease-causing mutations in patients with complex I deficiency.
摘要
线粒体复合物 I 缺陷是氧化磷酸化系统最常见的缺陷。我们报告了一例 Leigh 综合征患者，其在培养的成纤维细胞和肌肉组织中表现出复合物 I 缺陷。为了寻找复合物 I 缺陷的遗传原因，我们筛选了线粒体 DNA 和复合物 I 的核编码亚基。我们在编码复合物 I 辅助亚基的 NDUFA10 基因中发现了复合杂合突变。第一个突变破坏了起始密码子，第二个突变导致了氨基酸取代。患者的成纤维细胞显示复合物 I 的数量和活性减少，以及组装紊乱。这些结果表明，NDUFA10 是筛选复合物 I 缺陷患者致病突变的一个新的候选基因。
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