APOLIPOPROTEIN-A-I DEFICIENCY DUE TO A CODON-84 NONSENSE MUTATION OF THE APOLIPOPROTEIN-A-I GENE
APOLIPOPROTEIN-A-I DEFICIENCY DUE TO A CODON-84 NONSENSE MUTATION OF THE APOLIPOPROTEIN-A-I GENE
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DOI：
10.1073/pnas.88.7.2793
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发表时间：
1991-04-01
影响因子：
11.1
通讯作者：
HAMAGUCHI, H
中科院分区：
文献类型：
--
作者：
MATSUNAGA, T;HIASA, Y;HAMAGUCHI, H
对一名女性载脂蛋白A-I（apoA-I）缺乏症和过早动脉粥样硬化患者的分子遗传缺陷进行了检查。 她的父母是第一代表兄妹。 她的血浆密度分数为1.063至1.21 g/ml，SDS/PAGE上不含apoA-I，也不含可测量的高密度脂蛋白胆固醇。 Southern印迹杂交显示患者apoA-I基因无明显异常，apoA-I基因区域限制性片段长度多态性单倍型纯合性。 PCR扩增后测序结果显示患者apoA-I基因第4外显子第84位密码子无义突变（CAG -> TAG，Gln -> stop），第3外显子第37位密码子错义突变（GCC -> ACC，Ala -> Thr）。 等位基因特异性寡核苷酸探针斑点杂交的数据表明，她是纯合的apoA-I基因的两个突变。 在60例apoA-I和高密度脂蛋白胆固醇水平正常的对照组中，有6例存在apoA-I基因第37位密码子的错义突变，提示该错义突变是多态性的，与apoA-I缺乏症无关。 这些结果表明，载脂蛋白A-I基因的纯合性与密码子84无义突变导致载脂蛋白A-I和高密度脂蛋白胆固醇的患者缺乏。
The molecular genetic defect of a female patient with apolipoprotein A-I (apoA-I) deficiency and premature atherosclerosis was examined. Her parents were first cousins. Her plasma density fraction from 1.063 to 1.21 g/ml contained no apoA-I on SDS/PAGE and no measurable high density lipoprotein cholesterol. Southern blot hybridization showed no gross abnormality to be present in the patient's apoA-I gene and homozygosity for a haplotype of restriction fragment length polymorphisms in the apoA-I gene region. Sequencing after amplification by PCR revealed a codon 84 nonsense mutation (CAG --> TAG, Gln --> stop) of exon 4 and a codon 37 missense mutation (GCC --> ACC, Ala --> Thr) of exon 3 in the patient's apoA-I gene. The data from dot-blot hybridization with allele-specific oligonucleotide probes indicated that she was homozygous for the apoA-I gene with regard to the two mutations. The codon 37 missense mutation was also detected in the apoA-I gene of 6 out of 60 controls, who all had normal levels of apoA-I and high density lipoprotein cholesterol, suggesting that the missense mutation is polymorphic and not associated with apoA-I deficiency. These findings indicate that homozygosity for the apoA-I gene with codon 84 nonsense mutation causes the deficiency of apoA-I and of high density lipoprotein cholesterol in the patient.