An Insight into the Symptomatology of β-Thalassaemia Major: Molecular Genetic Basis of the Disease – III

Shamsi, Tahir; Ansari, Saqib Hussain; Hussain, Zeeshan

doi:10.21089/njhs.31.0001

Cited by 1 publication

(1 citation statement)

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“…Clinvar also demonstrated that this variant may cause loss of protein expression. It was also known to be instigating for β+thalassemia in Pakistani populations in which a slight decrement in the synthesis of β-chains occurs resulting in mild to intense hepato-splenomegaly and patients show higher total HB alpha chain 38 . In East Asians and Asian Indians, this variant was found to be responsible for the β 0 phenotype, in which no production of β-chains occurs 39 .…”

Section: Discussionmentioning

confidence: 99%

Mutational analysis of hemoglobin genes and functional characterization of detected variants, through in-silico analysis, in Pakistani beta-thalassemia major patients

Ejaz,

Abdullah,

Usman

et al. 2023

Sci Rep

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Thalassemia is one of the most prevalent genetic disorders worldwide. The present study aimed to explore the mutational spectrum of all hemoglobin (HB) encoding genes and to identify the potentially damaging and pathogenic variants in the beta (β)-thalassemia major patients and thalassemia minor carriers of Southern Punjab, Pakistan. A total of 49 β-thalassemia major patients and 49 carrier samples were screened for the identification of HBA1, HBA2, HBB, HBD, HBE1, HBG1 and HBG2 variants by NGS. PCR was performed for the amplification of HB encoding genes and the amplified product of 13 patients and 7 carrier samples were processed for the Sanger sequencing. Various bioinformatics tools and databases were employed to reveal the functional impact and pathogenicity potential of the observed variants. Results depicted a total of 20 variants of HB-related genes by NGS and 5 by Sanger sequencing in thalassemia patients. While 20 variants by NGS and 3 by Sanger were detected in carriers. Few known genetic variants of HB-encoding genes are being reported for the first time in Pakistani thalassemia patients and carriers. However, two novel HBB variants c.375A>C (p.P125P) and c.*61T>G and a novel variant of HBE1 (c.37A>T (p.T13S)) were also documented. Pathogenicity analysis predicted the pathogenic potential of HBB variants (c.47G>A (p.W16*), c.27-28insG (p. S10fs), and c.92+5G>C) for β thalassemia. The study of functional impact indicated that these HBB variants result in the premature termination of translation leading to the loss of functional β-globin protein. It is therefore suggested that the pathogenic HBB variants, identified during present study, can be employed for the diagnosis, carrier screening, and planning therapy of thalassemia.

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Section: Discussionmentioning

confidence: 99%