■β0-地中海贫血缺失去除5'β-珠蛋白启动子通常呈现具有高血红蛋白(Hb)A2和HbF水平的表型。我们报告了大量具有3.4kb缺失的β0地中海贫血的分子特征和表型基因型相关性。
■总共148个科目,包括127个杂合子,20例HbE-β-地中海贫血患者,和一个α-珠蛋白基因三重复的双杂合子,被招募。进行Hb和DNA分析以鉴定地中海贫血突变和四个高HbF单核苷酸多态性(SNP),包括γ-珠蛋白启动子处的四个碱基对缺失(-AGCA),OR51B6基因的rs5006884,-158Gγ-XmnI,3'Aγ-珠蛋白基因和5'δ-珠蛋白基因之间的BCL11A结合基序(TGGTCA)。
■发现具有3.4kb缺失的杂合β0-地中海贫血和HbE-β0-地中海贫血具有显着更高的Hb,血细胞比容,平均红细胞体积,与其他突变相比,平均红细胞血红蛋白和HbF值。具有3.4kb缺失的杂合β0-地中海贫血和α-地中海贫血的共同遗传与更高的MCV和MCH值相关。HbE-β0-地中海贫血患者具有非输血依赖性地中海贫血表型,无输血时平均Hb约为10g/dL。迄今为止尚未描述的双杂合β0-地中海贫血,具有3.4kb缺失和α-珠蛋白基因三联,表现为普通的β-地中海贫血性状。大多数受试者具有所检查的四个高HbFSNP的野生型序列。在具有和不具有这些SNP的受试者之间没有观察到HbF的显著差异。5'β-珠蛋白启动子的去除可能是这种异常表型的原因。
■结果表明,具有3.4kb缺失的β0-地中海贫血是轻度的β-地中海贫血等位基因。此信息应在遗传咨询和产前地中海贫血诊断中提供。
β 0-thalassemia deletion removing 5´β-globin promoter usually presents phenotype with high hemoglobin (Hb) A2 and Hb F levels. We report the molecular characteristics and phenotype-genotype correlation in a large cohort of the β 0-thalassemia with 3.4 kb deletion.
A total of 148 subjects, including 127 heterozygotes, 20 Hb E-β-thalassemia patients, and a double heterozygote with α-globin gene triplication, were recruited. Hb and DNA analysis were performed to identify thalassemia mutations and four high Hb F single nucleotide polymorphisms (SNPs) including four base pair deletion (-AGCA) at A γ-globin promoter, rs5006884 on OR51B6 gene, -158 G γ-XmnI, BCL11A binding motifs (TGGTCA) between 3´A γ-globin gene and 5´δ-globin gene.
It was found that heterozygous β 0-thalassemia and Hb E-β 0-thalassemia with 3.4 kb deletion had significantly higher Hb, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and Hb F values as compared with those with other mutations. Co-inheritance of heterozygous β 0-thalassemia with 3.4 kb deletion and α-thalassemia was associated with even higher MCV and MCH values. The Hb E-β 0-thalassemia patients carried a non-transfusion-dependent thalassemia phenotype with an average Hb of around 10 g/dL without blood transfusion. A hitherto undescribed double heterozygous β 0-thalassemia with 3.4 kb deletion and α-globin gene triplication presented as a plain β-thalassemia trait. Most of the subjects had wild-type sequences for the four high Hb F SNPs examined. No significant difference in Hb F was observed between those of subjects with and without these SNPs. Removal of the 5´β-globin promoter may likely be responsible for this unusual phenotype.
The results indicate that β 0-thalassemia with 3.4 kb deletion is a mild β-thalassemia allele. This information should be provided at genetic counseling and prenatal thalassemia diagnosis.