A mutation in the human heme A:farnesyltransferase gene (COX10 ) causes cytochrome c oxidase deficiency.
A mutation in the human heme A:farnesyltransferase gene (COX10 ) causes cytochrome c oxidase deficiency.
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DOI：
10.1093/hmg/9.8.1245
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发表时间：
2000-05
影响因子：
3.5
通讯作者：
I. Valnot;J. C. Kleist-Retzow;A. Barrientos;M. Gorbatyuk;J. Taanman;B. Mehaye;P. Rustin;A. Tzagoloff;Arnold Munnich;A. Rötig
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文献类型：
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作者：
I. Valnot;J. C. Kleist-Retzow;A. Barrientos;M. Gorbatyuk;J. Taanman;B. Mehaye;P. Rustin;A. Tzagoloff;Arnold Munnich;A. Rötig
细胞色素c氧化酶（考克斯）缺陷被发现在临床和遗传异质组线粒体疾病。迄今为止，仅描述了引起考克斯缺陷的两个核基因中的突变。我们在这里报告的遗传连锁研究的一个血缘家庭与一个孤立的考克斯缺陷和随后的鉴定突变的第三个核基因引起的酶的缺乏。全基因组纯合性搜索使我们能够将疾病基因定位到染色体17p13.1-q11.1（Z（max）= 2.46; θ = 0.00，位于基因座D17 S799）。该区域包括两个基因，SCO 1和COX 10，编码参与考克斯组装的蛋白质。突变分析，然后在酵母中的互补研究允许我们归因于考克斯缺陷的纯合错义突变的COX 10基因。该基因编码血红素A：法尼基转移酶，其催化血红素转化为酶的血红素A辅基的第一步。所有三个核基因现在与孤立的考克斯缺乏症都参与了考克斯的成熟和组装，强调了这些基因在考克斯病理学中的主要作用。
Cytochrome c oxidase (COX) defects are found in a clinically and genetically heterogeneous group of mitochondrial disorders. To date, mutations in only two nuclear genes causing COX deficiency have been described. We report here a genetic linkage study of a consanguineous family with an isolated COX defect and subsequent identification of a mutation in a third nuclear gene causing a deficiency of the enzyme. A genome-wide search for homozygosity allowed us to map the disease gene to chromosome 17p13.1-q11.1 (Z (max)= 2.46; theta = 0.00 at the locus D17S799). This region encompasses two genes, SCO1 and COX10, encoding proteins involved in COX assembly. Mutation analysis followed by a complementation study in yeast permitted us to ascribe the COX deficiency to a homozygous missense mutation in the COX10 gene. This gene encodes heme A:farnesyltransferase, which catalyzes the first step in the conversion of protoheme to the heme A prosthetic groups of the enzyme. All three nuclear genes now linked to isolated COX deficiency are involved in the maturation and assembly of COX, emphasizing the major role of such genes in COX pathology.