MUTATION OF A NUCLEAR SUCCINATE-DEHYDROGENASE GENE RESULTS IN MITOCHONDRIAL RESPIRATORY-CHAIN DEFICIENCY
MUTATION OF A NUCLEAR SUCCINATE-DEHYDROGENASE GENE RESULTS IN MITOCHONDRIAL RESPIRATORY-CHAIN DEFICIENCY
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DOI：
10.1038/ng1095-144
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发表时间：
1995-10-01
期刊：
影响因子：
30.8
通讯作者：
ROTIG, A
中科院分区：
文献类型：
--
作者：
BOURGERON, T;RUSTIN, P;ROTIG, A
我们现在报告了琥珀酸脱氢酶(SDH)核编码黄素蛋白(FP)亚单位基因突变，这两个兄弟姐妹的复杂II缺陷表现为Leigh综合征。两名患者均为FP亚基Arg554Trp替换纯合子。他们的父母(堂兄弟)是杂合子，突变发生在蛋白质的一个保守区域，在120名对照组中缺失。用突变的FP基因转化SDH酵母菌株，观察了Arg对Trp的取代对SDH催化活性的不利影响。FP亚单位基因在人类基因组(3q29；5p15)中复制，只有位于5号染色体上的基因在人-仓鼠体细胞杂交中表达。这是首次报道核基因突变导致人类线粒体呼吸链缺陷。
We now report a mutation in the nuclear-encoded flavoprotein (Fp) subunit gene of the succinate dehydrogenase (SDH) in two siblings with complex II deficiency presenting as Leigh syndrome. Both patients were homozygous for an Arg554Trp substitution in the Fp subunit. Their parents (first cousins) were heterozygous for the mutation that occurred in a conserved domain of the protein and was absent from 120 controls. The deleterious effect of the Arg to Trp substitution on the catalytic activity of SDH was observed in a SDH- yeast strain transformed with mutant Fp cDNA. The Fp subunit gene is duplicated in the human genome (3q29; 5p15), with only the gene on chromosome 5 expressed in human-hamster somatic cell hybrids. This is the first report of a nuclear gene mutation causing a mitochondrial respiratory chain deficiency in humans.