α0 Thalassaemia as a result of a novel 11.1 kb deletion eliminating both of the duplicated α globin genes
α0 Thalassaemia as a result of a novel 11.1 kb deletion eliminating both of the duplicated α globin genes
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DOI：
10.1136/jcp.2003.12856
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发表时间：
2004-02-01
影响因子：
3.4
通讯作者：
Xu, XM
中科院分区：
文献类型：
--
作者：
Jia, SQ;Li, J;Xu, XM
目的： 鉴定一个新的 11.1 kb 缺失，该缺失消除了两个重复的 α 珠蛋白基因，从而在一个中国家庭的四个携带者中产生典型的 α(0) 地中海贫血表型。方法：对所有家庭成员进行了血液学调查。通过聚合酶链反应（PCR）筛选七种常见形式的α地中海贫血，并使用Southern印迹分析α珠蛋白基因簇。对整个α1和α1球蛋白基因区域进行DNA序列分析，并使用逆转录（RT）-PCR研究α和β球蛋白基因的转录水平。结果：发现断点位于α球蛋白基因簇（NG_000006）的坐标31695-31724和42846-42867之间， 总共删除了约11135个核苷酸。这些序列涉及 (CA)(n) 重复，表明存在同源重组事件。 RT-PCR分析给出了杂合子中α珠蛋白基因的转录水平与SEA缺失杂合子的转录水平相当，证实连接的α珠蛋白基因对没有输出α珠蛋白。该家族所有四名携带者的 PCR 诊断均证实了这一新缺失的杂合性。结论：这种罕见突变构成了一种额外的异质性缺陷，导致中国人群中的 α 地中海贫血。
Aims: To characterise a novel 11.1 kb deletion that eliminated both of the duplicated alpha globin genes, giving rise to a typical alpha(0) thalassaemia phenotype in four carriers from a Chinese family.Methods: Haematological investigations were carried out on all family members. The seven common forms of alpha thalassaemia were screened for by the polymerase chain reaction (PCR) and Southern blotting was used to analyse the alpha globin gene cluster. DNA sequence analysis of the entire alpha1 and alpha1 globin gene region was carried out and reverse transcription (RT)-PCR was used to investigate the transcription levels of the alpha and beta globin genes.Results: The breakpoints were found to lie between coordinates 31695-31724 and 42846-42867 of the alpha globin gene cluster (NG_000006), with a total of about 11135 nucleotides deleted. These sequences are involved in (CA)(n) repeats, suggesting a homologous recombination event. RT-PCR analysis gave a transcription level of the alpha globin gene in heterozygotes comparable with that of SEA deletion heterozygotes, confirming no output of alpha globin from the linked pair of alpha globin genes. The heterozygosity for this novel deletion was confirmed by PCR diagnosis in all four carriers from this family.Conclusions: This rare mutation constitutes an additional heterogeneous defect causing alpha thalassaemia in the Chinese population.