HBB Gene Mutations and Their Impact on Phenotype and Protein Function in β-Thalassemia Families from Dera Ismail Khan, Pakistan

Authors

• Muhammad Ayaz, Department of Immunology, Hebei Medical University, Hebei 050017, ChinaFollow
• Muhammad Muzammal, Gomal Centre of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29050, PakistanFollow
• Maria Shafiq, Gomal Medical College, Dera Ismail Khan 29220, PakistanFollow
• Nisar Ahmad, Furong Laboratory, Centre for Medical Genetics, School of Life Sciences, Central South University, Changsha 410078, China
• Dua Iman, Gomal Centre of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29050, PakistanFollow
• Maria Faraz, Gomal Centre of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29050, Pakistan
• Yaser Uddin Hoti, Punjab Institute of Neurosciences, Lahore 54000, PakistanFollow
• Sami Siraj, Institute of Biomedical Sciences, Khyber Medical University, Peshawar 25120, PakistanFollow
• Muzammil Ahmad Khan, . Gomal Centre of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29050, Pakistan 3. Gomal Medical College, Dera Ismail Khan 29220, PakistanFollow
• Jabbar Khan, Institute of Biological Sciences, Gomal University, Dera Ismail Khan 29050, PakistanFollow

Abstract

The current genetic study aimed to screen out the genetic basis of ß-thalassemia in five unrelated consanguineous Pakistani families. Blood samples were collected, and targeted Sanger Sequencing of the HBB gene was done. Serum Interleukin-6 (IL-6) and quantitative measurements of T Helper and T Suppressor Lymphocytes were also carried out. Additionally, in silico analysis, including protein modeling, Protein-Protein docking, and Multiple sequence alignment, was also performed. Genetic analysis identified a homozygous mutation c.92+5G > C (IVS-I+5 G > C) in families 1, 2, and 3, which resulted in β⁺/ β⁺ Thalassemia Intermedia phenotype. While in the case of family 4, we identified a c.92G > C + c.92+5G > C (IVS-I+5 G > C) mutation in a compound heterozygous state that led to β⁺ Thalassemia Intermedia phenotype. However, in the case of family 5, a rare frameshift homozygous mutation c.17_18delCT was identified, reported only in the Balochi ethnic group throughout the history of thalassemia in Pakistan. Heterogeneous quantities of IL-6, T helper lymphocytes, and T Suppressor Lymphocytes were found in all the patients. This study offers an effective incentive to establish mutation detection as well as prenatal diagnosis (PND) centers on a larger scale, in the different ethnicities residing in the district Dera Ismail Khan (D. I. Khan), KP, Pakistan

Recommended Citation

Ayaz, Muhammad; Muzammal, Muhammad; Shafiq, Maria; Ahmad, Nisar; Iman, Dua; Faraz, Maria; Hoti, Yaser Uddin; Siraj, Sami; Khan, Muzammil Ahmad; and Khan, Jabbar (2026) "HBB Gene Mutations and Their Impact on Phenotype and Protein Function in β-Thalassemia Families from Dera Ismail Khan, Pakistan," Makara Journal of Science: Vol. 30: Iss. 3, Article 2.
DOI: 10.7454/mss.v30i3.3118
Available at: https://scholarhub.ui.ac.id/science/vol30/iss3/2