Genotype-Phenotype Correlation of Β-Globin Mutations and Hematological Parameters in Iraqi Β-Thalassemia Patients.

BACKGROUND/AIMS: β-Thalassemia is a common hemoglobin disorder distributed worldwide and caused by mutations in the HBB gene that reduce or abolish β-globin chain synthesis, resulting in chronic hemolytic anemia, ineffective erythropoiesis, and variable clinical severity. Although the molecular spectrum of β-thalassemia has been extensively investigated, data correlating β-globin mutations with hematological characteristics in Iraqi patients remain limited. This study aimed to evaluate genotype-phenotype correlations by integrating molecular mutation analysis with hematological and biochemical profiling in an Iraqi β-thalassemia cohort.

METHODS

A cross-sectional study was conducted between September and November 2025 at the Hematology Department, University of Baghdad. Fifty patients with β-thalassemia were initially recruited, of whom 22 fulfilled the inclusion criteria and consented to participate (4 males and 18 females; age range, 18-68 years). Hematological parameters, HbA₂ and HbF levels, serum iron and ferritin concentrations, and β-globin gene mutations were analyzed. Mutation screening was performed using amplification refractory mutation system polymerase chain reaction (ARMS-PCR). Statistical analyses were conducted to evaluate genotype-phenotype associations.

RESULTS

Patients exhibited a predominantly microcytic, hypochromic hematological profile, with a mean hemoglobin concentration of 11.1 ± 1.4 g/dL, a mean MCV of 63.5 ± 0.78 fL, a mean MCH of 20.2 ± 0.25 pg, and elevated RDW values (17.9 ± 0.23%), consistent with anisocytosis. HbA₂ levels ranged from 3.5% to 7.2% (mean, 5.4 ± 0.25%) as determined by HPLC, whereas HbF levels ranged from 0.3% to 5.6% (mean, 1.4 ± 0.17%). HPLC provided more reliable HbA₂ quantification than alkaline electrophoresis. Serum iron and ferritin levels showed considerable interindividual variability. β-Globin mutations were identified in 68.2% of patients, with IVS-I-6 being the most frequent mutation (45.5%), followed by CD39. No significant associations were observed between genotype and sex, profession, ethnicity, or place of residence. In contrast, age-group distribution differed significantly.

CONCLUSION

This study demonstrated considerable phenotypic heterogeneity among Iraqi patients with β-thalassemia and identified IVS-I-6 as the predominant β-globin mutation in this cohort. The absence of significant genotype-phenotype associations for most clinical variables suggests that additional genetic and environmental modifiers may contribute to disease expression. Combined molecular and hematological evaluation may improve the diagnostic characterization and classification of patients with β-thalassemia.