A novel mutation of-73(A→T) in the CCAAT box of the β-globin gene identified in a patient with the mild β-thalassemia intermedia

The beta-thalassemia is one of the most common autosomal recessive disorders in Southern China. The point mutation of beta-globin gene is the commonest molecular pathogenic mechanism. In Chinese population, over 30 mutations have now been identified. In this paper, we describe a novel beta(++)-thalassemia mutation of -73(A -> T) within the conserved CCAAT box at position -76 to -72 from the cap site of the beta-globin gene. The proband, an 8-year-old Chinese boy, was a compound heterozygote of this promoter mutation and a common beta(0)-thalassemia mutation of codon 41/42(-TCTT). He had a mild thalassemia intermedia phenotype and was transfusion independent with a hemoglobin (Hb) level of 9.4 g/dl, mean corpuscular volume (MCV) of 55.2 fl, and mean corpuscular hemoglobin (MCH) of 17.5 pg. His mother and two maternal uncles were carriers of -73(A -> T) mutation in beta-globin gene with hematological phenotype of silent beta-thalassemia. Real-time quantitative reverse transcript polymerase chain reaction (RT-PCR) analysis showed a slightly reduced beta-globin messenger RNA (mRNA) level (19.35%) in three heterozygotes compared with that in normal subjects. In restriction fragment length polymorphism (RFLP) haplotype analysis, the results indicated that this promoter mutation might be linked to the absence of BamHI-3'beta restriction site.