A Novel 5 kb Deletion in the β-Globin Gene Cluster Identified in a Chinese Patient
A Novel 5 kb Deletion in the β-Globin Gene Cluster Identified in a Chinese Patient
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DOI：
10.1080/03630269.2022.2118604
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发表时间：
2022-10-07
期刊：
影响因子：
1
通讯作者：
Du, Li
中科院分区：
文献类型：
--
作者：
Bao, Xiu-Qin;Wang, Ji-Cheng;Du, Li
β-地中海贫血（β-Thalassemia，β-地贫）是我国南方热带和亚热带地区的一种高度流行的疾病，主要由β-珠蛋白基因簇的点突变引起。然而，大的缺失也被发现有助于某些类型的β-地中海。我们使用多重连接依赖探针扩增（MLPA）技术在一名中国患者的β-珠蛋白簇中发现了一个新的5 kb缺失，并通过单分子实时荧光（SMRT）测序、缺口聚合酶链反应（gap-PCR）和桑格测序对其进行了表征。该缺失位于11号染色体（GRCh 38）上的位置5226189和5231091之间，从5'非翻译区（5' UTR）上游4kb延伸至β-珠蛋白基因的第二内含子。该缺失的患者表现为红细胞减少和低色素红细胞，以及相对较高的Hb F和Hb A（2）水平。我们的研究表明，SMRT测序是一个有用的工具，准确检测大缺失。我们的研究拓宽了缺失型β-地中海贫血的范围，并为进一步研究β-珠蛋白簇的功能提供了一个视角。
beta-Thalassemia (beta-thal), a highly prevalent disease in tropical and subtropical regions of Southern China, is caused mainly by point mutations in the beta-globin gene cluster. However, large deletions have also been found to contribute to some types of beta-thal. We identified a novel 5 kb deletion in the beta-globin cluster in a Chinese patient using multiplex ligation-dependent probe amplification (MLPA), and characterized it with single molecule real-time (SMRT) sequencing, gap-polymerase chain reaction (gap-PCR) and Sanger sequencing. The deletion was located between positions 5226189 and 5231091 on chromosome 11 (GRCh38), extending from 4 kb upstream of the 5' untranslated region (5'UTR) to the second intron of the beta-globin gene. The patient with this deletion presented with microcytosis and hypochromic red cells, as well as relatively high Hb F and Hb A(2) levels. Our research indicated that SMRT sequencing is a useful tool for accurate detection of large deletions. Our study broadens the spectrum of deletional beta-thalassemias and provides a perspective for further study of the function of the beta-globin cluster.