Demonstration of a new pathogenic mutation in human complex I deficiency: A 5-bp duplication in the nuclear gene encoding the 18-kD (AQDQ) subunit
Demonstration of a new pathogenic mutation in human complex I deficiency: A 5-bp duplication in the nuclear gene encoding the 18-kD (AQDQ) subunit
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DOI：
10.1086/301716
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发表时间：
1998-02-01
影响因子：
9.8
通讯作者：
Smeitink, J
中科院分区：
文献类型：
--
作者：
van den Heuvel, L;Ruitenbeek, W;Smeitink, J
本文报道了人线粒体呼吸链复合体I亚基18-kD(AQDQ)亚基编码基因的克隆、染色体定位和突变，该基因编码一个由175个氨基酸组成的开放阅读框，编码一个相对分子质量为23.2kD的蛋白质。它的基因被定位在5号染色体上。在1例复杂的I-缺乏症患者中，发现了一个纯合的5-碱基重复序列，破坏了18-kD基因中的一个共同的磷酸化位点。患者表现出正常的肌肉形态和显著的非特异性致死性进行性表型，体液中乳酸浓度没有增加，孩子的父母是突变的杂合子。在其他19例复合体I缺陷患者中，未发现18-kD基因突变。
We report the cDNA cloning, chromosomal localization, and a mutation in the human nuclear gene encoding the 18-kD (AQDQ) subunit of the mitochondrial respiratory chain complex I, The cDNA has an open reading frame of 175 amino acids and codes for a protein with a molecular mass of 23.2 kD. Its gene was mapped to chromosome 5. A homozygous 5-bp duplication, destroying a consensus phosphorylation site, in the 18-kD cDNA was found in a complex I-deficient patient. The patient showed normal muscle morphology and a remarkably nonspecific fatal progressive phenotype without increased lactate concentrations in body fluids, The child's parents were heterozygous for the mutation. In 19 other complex I-deficient patients, no mutations were found in the 18-kD gene.