Nonsense codon mutations in the terminal exon of the beta-globin gene are not associated with a reduction in beta-mRNA accumulation: a mechanism for the phenotype of dominant beta-thalassemia.
Nonsense codon mutations in the terminal exon of the beta-globin gene are not associated with a reduction in beta-mRNA accumulation: a mechanism for the phenotype of dominant beta-thalassemia.
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β-珠蛋白基因末端外显子中的无义密码子突变与β-mRNA积累的减少无关：这是显性β-地中海贫血表型的机制。
DOI：
10.1182/blood.v83.8.2031.bloodjournal8382031
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发表时间：
1994
期刊：
影响因子：
20.3
通讯作者：
S. Thein
中科院分区：
文献类型：
--
作者：
Georgina W. Hall;S. Thein
我们目前在体内的证据表明，有没有减少β-珠蛋白基因的末端外显子中的无义密码子的患者β-mRNA的积累。使用逆转录酶/聚合酶链反应（RT-PCR），β-珠蛋白cDNA分离的网织红细胞的β-珠蛋白基因的外显子II和III中的无义密码子突变的杂合子。发现导致外显子II [β（0）39（C-T）和F/S71/72（+A）]翻译提前终止的突变杂合子的临床无症状个体几乎没有突变的β-cDNA，而具有中间型地中海贫血临床表型的外显子III无义密码子突变[β 121（G-T）和β 127（C-T）]的患者的突变和正常β-地中海贫血水平相当cDNA。来自外显子III中无义密码子突变患者的突变β-mRNA的翻译将产生截短的β-珠蛋白链，这可以解释在这些个体中观察到的更严重的表型。
We present in vivo evidence that there is no reduction in beta-mRNA accumulation in patients with nonsense codons in the terminal exon of the beta-globin gene. Using reverse transcriptase/polymerase chain reaction (RT-PCR), beta-globin cDNA was isolated from the reticulocytes of individuals heterozygous for nonsense codon mutations in exons II and III of the beta-globin gene. Clinically asymptomatic individuals heterozygous for mutations causing premature termination of translation in exon II [beta(0)39(C-T) and F/S71/72(+A)] were found to have almost no mutant beta-cDNA, whereas patients with nonsense codon mutations in exon III [beta 121(G-T) and beta 127(C-T)] with the clinical phenotype of thalassemia intermedia had comparable levels of mutant and normal beta-cDNA. Translation of the mutant beta-mRNA from patients with nonsense codon mutations in exon III would give rise to truncated beta-globin chains, which could explain the more severe phenotype seen in these individuals.