Genetic basis of ß-thalassemia in families of pashtun ethnicity in Dera Ismail Khan district of Khyber Pakhtun-Khwa province, Pakistan

ABSTRACT

Objectives

The objective of current genetic research was to verify the genetic basis of ß-thalassemia and its pattern of inheritance in families of Pashtun ethnicity in District Dera Ismail Khan, Pakistan.

Methodology

Blood samples from clinically diagnosed five unrelated ß-thalassemia families were collected and target Sanger Sequencing of HBB gene was done. Moreover, in silico analysis including protein modeling and Protein-Protein docking was aslo performed.

Results and Discussion

Clinical analysis of patients from family 1,2, 4, and 5 revealed Thalassemia Intermedia, while patient from family 3 was suffering from thalassemia major. The average Hb concentrations between the cases that were severe were found to be a little lower (6.3 mg/dl) than the patients with milder clinical manifestations (7.6 ± 1.4). Genetic analysis in family 1 identified compound heterozygous mutation of HBB (NM_000518) i.e. c.20A>T +c.92 G>A, in family 2 and 4 compound heterozygous mutations c.20A>T + c.27_28insG, in family 3 homozygous mutation c.27_28insG, while in family 5 we identified homozygous mutation c.92 + 5 G>C (IVS-1 + 5 G>C).

Conclusion

This study offers an effective incentive to establish a mutation detection as well as prenatal diagnosis (PND) centers at a larger scale in the Pashtun ethnicity residing in District Dera Ismail Khan, Pakistan.

KEYWORDS:

• HBB
• Pakistani
• Pashtun
• ß-thalassemi
• Mutation

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Muhammad Ayaz: family recruitment and genetic analysis. Muhammad Muzammal: family recruitment, genetic analysis, software and drafting. Sumaya Fatima and Sana Fatima: drafting. Jabbar Khan and Lin Wei: overall supervision. Muzammil Ahmad Khan: drafting. Sami Siraj: genetics analysis. Muhammad Ishaq Shah and Zia ur Rehman: DNA extraction. All authors agree to be accountable for all aspects of the work.

Acknowledgments

We are thankful to the volunteer families for participating in this study.

Ethical approval

This study was approved by Ethical Review Board Gomal University, D. I. Khan, KP, Pakistan and all methods were performed in accordance with the relevant guidelines and regulations.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/17474086.2023.2241639

Data availability statement

All data will be provided from the authors upon request.

Additional information

Funding

This paper was not funded.