Phenotype of mutations in the promoter region of the β-globin gene
Phenotype of mutations in the promoter region of the β-globin gene
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DOI：
10.1136/jclinpath-2017-204378
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发表时间：
2017-10-01
影响因子：
3.4
通讯作者：
Martinez, Rafael
中科院分区：
文献类型：
--
作者：
Ropero, Paloma;Erquiaga, Sara;Martinez, Rafael
背景β（+）地中海贫血的特征在于β链的产生减少，其减少可由启动子区（CACCC或TATA盒）中的突变引起，并且根据β-珠蛋白链减少的程度被分类为轻度或沉默。在这两种情况下，这些突变的纯合子或复合杂合子通常患有中间型地中海贫血。通常诊断是在成年甚至老年。在启动子区的37个改变已经被描述到目前为止。目的在这份报告中，我们描述了在马德里的一家医院中发现的β-珠蛋白基因的启动子区的突变。方法在1998年和2015年之间，超过9000血液样本进行了全血细胞计数分析，并进行血红蛋白电泳和高效液相色谱法。β和G γ-珠蛋白基因的遗传分析通过自动测序进行，α基因的情况下，通过多重PCR进行。结果35个样品显示β-珠蛋白基因的启动子区域的突变，总共鉴定出6种不同的突变：一个在远端CACCC盒中，两个在近端CACCC盒中，结论近端CACCC和TATA盒的任何改变都会导致β-珠蛋白链合成的中度减少，这已在中间型地中海贫血病例中得到证实，这些病例在生命的第二个十年出现中度临床病程。
Background beta(+)-Thalassaemia is characterised by reduced production of beta chains, which decrease can be caused by mutations in the promoter region (CACCC or TATA box), and is classified as mild or silent depending on the extent of beta-globin chain reduction. In both cases, homozygotes or compound heterozygotes for these mutations usually have thalassaemia intermedia. Frequently the diagnosis is made in adulthood or even in old age. A total of 37 alterations in the promoter region have been described so far.Aims In this report we describe the mutations found in the promoter region of the beta-globin gene in a single hospital in Madrid.Methods Between 1998 and 2015, more than 9000 blood samples were analysed for full blood count and underwent haemoglobin electrophoresis and high performance liquid chromatography. Genetic analysis of the beta and G gamma-globin genes was carried out by automatic sequencing and, in the case of alpha genes, by multiplex PCR.Results 35 samples showed mutation in the promoter region of the beta-globin gene, with a total of six different mutations identified: one in the distal CACCC box, two in the proximal CACCC box, three in the ATA box.Conclusions Any alterations in the proximal CACCC and TATA boxes lead to a moderate decrease in synthesis of the beta-globin chain, which has been demonstrated in cases of thalassaemia intermedia that have presented in the second decade of life with a moderate clinical course.