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; Mutation; Pakistani; Pashtun; ß-thalassemi.