Genotype and phenotype characteristics of homozygous and compound heterozygous β-thalassemia with 3.4 kb deletion Dear Editors, β-thalassemia is an inherited haemoglobin (Hb) disorders caused by deletional and non-deletional mutations in the β-globin gene leading to absent (β 0 -thalassemia) or decreased (β + -thalassemia) β-globin chain synthesis. Heterozygous β-thalassemia is symptomless and associated with elevated Hb A 2 . However, homozygous or compound heterozygous β-thalassemia is generally associated with transfusion dependent thalassemia major. 1 We received blood specimen of an adult female who had anaemia for thalassemia investigation. Ethical approval of the study was obtained from the Institutional Review
Background β0-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 β0-thalassemia with 3.4 kb deletion. Methods 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 Aγ-globin promoter, rs5006884 on OR51B6 gene, −158 Gγ-XmnI, BCL11A binding motifs (TGGTCA) between 3´Aγ-globin gene and 5´δ-globin gene. Results It was found that heterozygous β0-thalassemia and Hb E-β0-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 β0-thalassemia with 3.4 kb deletion and α-thalassemia was associated with even higher MCV and MCH values. The Hb E-β0-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 β0-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. Conclusions The results indicate that β0-thalassemia with 3.4 kb deletion is a mild β-thalassemia allele. This information should be provided at genetic counseling and prenatal thalassemia diagnosis.
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