REPORTING TWO RARE MUTATIONS WITH ASSOCIATED CLINICAL FEATURES IN BANGLADESHI HB E/Β THALASSEMIA PATIENTS

Md. Abdul Aziz; Nabiha Tasneem Khan; Waqar Ahmed Khan; Mustak Ibn Ayub; Sabina Yeasmin

doi:10.3329/brc.v10i1.70683

Authors

Md. Abdul Aziz Bangladesh Shishu Hospital and Institute, Sher-E-Bangla Nagar, Dhaka-1207
Nabiha Tasneem Khan Department of Genetic Engineering and Biotechnology, University of Dhaka
Waqar Ahmed Khan Bangladesh Shishu Hospital and Institute, Sher-E-Bangla Nagar, Dhaka-1207
Mustak Ibn Ayub Department of Genetic Engineering and Biotechnology, University of Dhaka
Sabina Yeasmin Department of Genetic Engineering and Biotechnology, University of Dhaka

DOI:

https://doi.org/10.3329/brc.v10i1.70683

Keywords:

hemoglobin E-beta thalassemia, rare mutation, thalassemia

Abstract

Thalassemia is one of the most common genetic disorders in Bangladesh. We have performed an investigation among 360 patients with Hb E/β-thalassemia to understand the heterogeneity in thalassemia severity among Bangladeshi patients. The analysis revealed that one of the common mutations CD26 (G>A) is found with two rare mutations HBB: c.-79A>G (-29A>G) and HBB: c.45_46insG (CD14/15 (+G)) in two patients individually which are not prevalent in geographically adjacent populations. Among these two rare mutations, -29A>G is located at the ‘TATA’ box region of the promoter sequence regulating transcription initiation and CD14/15 (+G) leads to a premature stop codon. We performed transcription factor binding site prediction analysis and found that ‘AP-1’, ‘c-Jun’, and ‘kr’ transcription factors bind at the ‘TATA’ box region. From this analysis, we can predict that -29A>G mutation can alter the level of HBB transcription whereas the CD14/15 (+G) mutation causes a truncated (and possibly non-functional) HBB protein. Aligned with such assumption, it was observed from patients’ medical history that, the patient who had CD14/15 (+G) and CD26 (G>A) mutations was severely blood transfusion-dependent whereas the patient carrying -29A>G and CD26 (G>A) mutations was moderately transfusion dependent. The comprehensive analysis of the mutations offers crucial insights and approaches for enhanced management of thalassemia among the Bangladeshi population.

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