Mutant NDUFS3 subunit of mitochondrial complex I causes Leigh syndrome
Mutant NDUFS3 subunit of mitochondrial complex I causes Leigh syndrome
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DOI：
10.1136/jmg.2003.014316
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发表时间：
2004-01-01
影响因子：
4
通讯作者：
Rustin, P
中科院分区：
文献类型：
--
作者：
Bénit, P;Slama, A;Rustin, P
呼吸链复合体I缺乏症是一种由线粒体或核基因突变引起的遗传异质性疾病。据报道，编码复合体I核心的14个亚基（7个线粒体基因和6个核基因）中有13个发生了突变，这些突变导致Leigh或Leigh样综合征或心肌病。本研究采用变性高效液相色谱和序列分析相结合的方法，对一系列复合物I缺乏患者的NDUFS3基因进行了研究。该基因（NADH脱氢酶铁硫蛋白3）编码复合体I核心的第七个也是最后一个亚基，该基因突变可导致晚发性Leigh综合征、视神经萎缩和复合体I缺乏。通过鉴定导致这些细胞中NDUFS3突变的疾病，证实了从妊娠后期培养的羊膜细胞中复合物I缺乏的生化诊断。虽然NDUFS3基因的突变导致Leigh综合征，但NDUFV2和NDUFS2基因的突变导致脑肌病和心肌病的临床表型不同。造成这些差异的原因尚不确定。
Respiratory chain complex I deficiency represents a genetically heterogeneous group of diseases resulting from mutations in mitochondrial or nuclear genes. Mutations have been reported in 13 of the 14 subunits encoding the core of complex I ( seven mitochondrial and six nuclear genes) and these result in Leigh or Leigh-like syndromes or cardiomyopathy. In this study, a combination of denaturing high performance liquid chromatography and sequence analysis was used to study the NDUFS3 gene in a series of complex I deficient patients. Mutations found in this gene ( NADH dehydrogenase iron-sulphur protein 3), coding for the seventh and last subunit of complex I core, were shown to cause late onset Leigh syndrome, optic atrophy, and complex I deficiency. A biochemical diagnosis of complex I deficiency on cultured amniocytes from a later pregnancy was confirmed through the identification of disease causing NDUFS3 mutations in these cells. While mutations in the NDUFS3 gene thus result in Leigh syndrome, a dissimilar clinical phenotype is observed in mutations in the NDUFV2 and NDUFS2 genes, resulting in encephalomyopathy and cardiomyopathy. The reasons for these differences are uncertain.