The haptoglobin-gene deletion responsible for anhaptoglobinemia
The haptoglobin-gene deletion responsible for anhaptoglobinemia
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DOI：
10.1086/301701
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发表时间：
1998-02-01
影响因子：
9.8
通讯作者：
Kimura, H
中科院分区：
文献类型：
--
作者：
Koda, Y;Soejima, M;Kimura, H
我们已经发现了一个等位基因缺失的haptaglobin（Hp）基因从个人与anhaptoglobinemia。Hp基因簇由触珠蛋白基因（Hp）的α链和β链以及触珠蛋白相关基因（Hpr）的α链和β链的编码区组成，从5'侧串联。Southern印迹和PCR分析表明，无触珠蛋白血症的个体是基因缺失的纯合子，并且基因缺失至少包括从Hp到Hpr或但不包括到Hpr β（Hp（del））的启动子区域。另外，我们在3个家系中发现7例低触珠蛋白血症患者，其中6例为Hp（2）/Hp（del）基因型。其中一个家系的表型和基因型显示父亲为低结合球蛋白血症（Hp 2）和Hp（2）/Hp（del），母亲为Hp 2 -1和Hp（1）/Hp（2），两个子女中的一个为低结合球蛋白血症（Hp 2）和Hp（2）/Hp（del），另一个子女为Hp 1和Hp（1）/Hp（del），显示Hpl患儿Hp表型的异常遗传。与从52名具有Hp 2表型的健康志愿者获得的水平（1.64 +/- 1.07 mg/ml）相比，Hp（2）/Hp（del）个体具有极低的Hp水平（平均值+/- SD = 0.049 +/- 0.043 mg/ml; n = 6），而具有Hp（1）/Hp（del）个体的血清Hp水平为0.50 mg/ml，这大约是来自Hp 1表型的对照血清中Hp水平（1.26 +/- 0.33 mg/ml; n = 9）的一半，显示基因剂量效应。经DNA测序发现Hp（2）/Hp（del）患者的另一个等位基因（Hp（2））在所有外显子上均无突变。在此基础上，很好地解释了无触珠蛋白血症的机制和Hp表型异常遗传的机制。然而，低触珠蛋白血症的机制仍不清楚。
We have found an allelic deletion of the haptaglobin (Hp) gene from an individual with anhaptoglobinemia. The Hp gene cluster consists of coding regions of the a chain and beta chain of the haptoglobin gene (Hp) and of the a chain and beta chain of the haptoglobin-related gene (Hpr), in tandem from the 5' side. Southern blot and PCR analyses have indicated that the individual with anhaptoglobinemia was homozygous for the gene deletion and that the gene deletion was included at least from the promoter region of Hp to Hpr or but not to Hpr beta (Hp(del)). In addition, we found seven individuals with hypohaptoglobinemia in three families, and the genotypes of six of the seven individuals were found to be Hp(2)/Hp(del). The phenotypes and genotypes in one of these three families showed the father to be hypohaptoglobinemic (Hp2) and Hp(2)/Hp(del), the mother to be Hp2-1 and Hp(1)/Hp(2), one of the two children to be hypohaptoglobinemic (Hp2) and Hp(2)/Hp(del), and the other child to be Hp1 and Hp(1)/Hp(del) showing an anomalous inheritance of Hp phenotypes in the child with Hpl. The Hp(2)/Hp(del) individuals had an extremely low level of Hp (mean +/- SD = 0.049 +/- 0.043 mg/ml; n := 6), compared with the level (1.64 +/- 1.07 mg/ml) obtained from 52 healthy volunteers having phenotype Hp2, whereas the serum Hp level of an individual with Hp(1)/Hp(del) was 0.50 mg/ml, which was approximately half the level of Hp in control sera from the Hp1 phenotype (1.26 +/- 0.33 mg/ml; n = 9), showing a gene-dosage effect. The other allele (Hp(2)) of individuals with Hp(2)/Hp(del) was found to have, in all exons, no mutation, by DNA sequencing. On the basis of the present study, the mechanism of anhaptoglobinemia and the mechanism of anomalous inheritance of Hp phenotypes were well explained. However, the mechanism of hypohaptoglobinemia remains unknown.