Abstract
In this report we have tried to explain the reasons behind the difference in the pattern of transfusion requirement between two members of a family with similar β-globin mutation. The father and younger son both are HbE-β, but the father never had transfusion, whereas the younger son takes transfusion monthly. Mother and the elder son are HbEE without any history of transfusion. β-globin mutations of all family members were determined by ARMS-PCR. These were reconfirmed by direct sequencing of β-globin gene. Father and younger son were found to be Cod 26 (G-A)/IVS 1-5 (G-C), whereas mother and elder son were found to be Cod 26 (G-A)/Cod 26 (G-A). XmnI sequencing also revealed that all members of the family were CC. Then, flow cytometry study of red blood cells (RBCs) was performed to measure the oxidative stress of the RBCs. This study was also done on the light and dense fractions of the RBC population of the father and younger son. It was seen that the younger son suffers severe oxidative stress, which can be explained by his higher transfusion requirement. From our work, we have established the importance of taking oxidative stress of RBCs into consideration to explain the clinical manifestation and progression of haemoglobin related diseases like thalassaemia.
Highlights
The HbE-β is one of the most common forms of haemoglobinopathies worldwide [1]
When we ran the total red blood cells (RBCs) from the four samples, we observed no significant difference in their annexin V-FITC binding, and the % PS exposure was not very different
To summarise this case study, we have seen that the genomics study of the family showed that the father (P1) and the younger son (P4) have the exactly identical mutation in their β globin gene, but the father has no clinical manifestation, whereas the younger son is severely anaemic and requires blood transfusion almost every month
Summary
The HbE is a splice variant of normal β globin protein. This cryptic splice site (related to HbE) is not normally used for mRNA processing. This new splice site competes with the normal splice site and produces a protein with a Lys instead of a Glu at position 26 [2]. This variant (HbE) is the protein, produced by the said mutation. When one of the nucleotides from the GT/⋅ ⋅ ⋅ /AG junction is modified the result is a total abolition of the splicing leading to a β0 thalassaemic defect
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