Jia S-Q, Li J, Mo Q-H, Liao C, Li L-Y, Xu X-M
Department of Medical Genetics, First Military Medical University, Guangzhou 510515, Guangdong, PR China.
J Clin Pathol. 2004 Feb;57(2):164-7. doi: 10.1136/jcp.2003.12856.
To characterise a novel 11.1 kb deletion that eliminated both of the duplicated alpha globin genes, giving rise to a typical alpha0 thalassaemia phenotype in four carriers from a Chinese family.
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.
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 11,135 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.
This rare mutation constitutes an additional heterogeneous defect causing alpha thalassaemia in the Chinese population.
鉴定一种新的11.1 kb缺失，该缺失消除了两个重复的α珠蛋白基因，导致一个中国家庭的四名携带者出现典型的α0地中海贫血表型。
对所有家庭成员进行血液学检查。通过聚合酶链反应（PCR）筛查α地中海贫血的七种常见形式，并用Southern印迹法分析α珠蛋白基因簇。对整个α1和α2珠蛋白基因区域进行DNA序列分析，并使用逆转录（RT）-PCR研究α和β珠蛋白基因的转录水平。
发现断点位于α珠蛋白基因簇（NG_000006）的坐标31695 - 31724和42846 - 42867之间，总共约11,135个核苷酸缺失。这些序列参与（CA）n重复，提示发生了同源重组事件。RT-PCR分析显示杂合子中α珠蛋白基因的转录水平与SEA缺失杂合子相当，证实来自一对相连的α珠蛋白基因没有α珠蛋白输出。通过PCR诊断在该家庭的所有四名携带者中证实了这种新缺失的杂合性。
这种罕见突变构成了中国人群中导致α地中海贫血的另一种异质性缺陷。
