A deletion in the human QP-C gene causes a complex III deficiency resulting in hypoglycaemia and lactic acidosis
A deletion in the human QP-C gene causes a complex III deficiency resulting in hypoglycaemia and lactic acidosis
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DOI：
10.1007/s00439-003-0946-0
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发表时间：
2003-07-01
期刊：
影响因子：
5.3
通讯作者：
Slama, A
中科院分区：
文献类型：
--
作者：
Haut, S;Brivet, M;Slama, A
线粒体呼吸链复合物III（泛喹啉-细胞色素c还原酶）由11个亚基组成，只有一个亚基（细胞色素B）由线粒体DNA编码。疾病的复杂III是比较罕见的，但仍然存在作为一个临床异质性组的疾病。到目前为止，还没有任何突变的核编码亚基已被描述。我们在这里报告的缺失在核基因UQCRB编码的人泛结合蛋白的复合物III（QP-C亚基或亚基VII）在一个血缘家庭与一个孤立的复合物III的缺陷。在先证者中，在cDNA的核苷酸338-341处鉴定出纯合的4-bp缺失，预测最后7个氨基酸的变化和在蛋白质的C-末端添加14个氨基酸的延伸。发现父母双方都是杂合子的缺失，这是不存在的55个控制。对先证者培养的皮肤成纤维细胞分离的线粒体进行的低温（-196 ℃）光谱研究显示，细胞色素B含量降低，提示QP-C亚基在组装或维持复合物III结构中的作用。
Mitochondrial respiratory chain complex III (ubiquinol-cytochrome c reductase) consists of 11 subunits, only one (cytochrome b) being encoded by the mitochondrial DNA. Disorders of complex III are comparatively rare but are nevertheless present as a clinically heterogeneous group of diseases. To date, no mutation in any of the nuclear-encoded subunits has been described. We report here a deletion in the nuclear gene UQCRB encoding the human ubiquinone-binding protein of complex III (QP-C subunit or subunit VII) in a consanguineous family with an isolated complex III defect. In the proband, a homozygous 4-bp deletion was identified at nucleotides 338-341 of the cDNA predicting both a change in the last seven amino acids and an addition of a stretch of 14 amino acids at the C-terminal end of the protein. Both parents were found to be heterozygous for the deletion, which was absent from 55 controls. Low temperature (-196degreesC) spectral studies performed on isolated mitochondria from cultured skin fibroblast of the proband showed a decreased cytochrome b content suggestive of a role for the QP-C subunit in the assembly or maintenance of complex III structure.