Copy number variations of six and seven α-globin genes in a family with intermedia and major thalassemia phenotypes

Background: Copy number variations in alpha-globin genes are results of unequal crossover between homologous segments in the alpha-globin gene cluster that misalign during the meiosis phase of the gametogenesis process. Reduction or augmentation of alpha-globin genes leads to imbalance of alpha/beta chains in hemoglobin tetramer and consequently attenuate or worsen the beta-thal clinical symptoms, respectively. Objective: Multiplications in alpha-globin genes have been found in some populations, justifying unexpected severe phenotype of beta-thal carriers. Study design: Unexpected severe phenotype in the family members may result from coexistence of extra alpha-globin genes, which is an important factor in the causation of thalassemia intermedia and major in heterozygous beta-thalassemia. Results: We described different multiplications in alpha-globin locus in an Iranian family with one, two or three extra alpha-globin genes (alpha alpha alpha/alpha alpha, alpha alpha alpha alpha/alpha alpha and alpha alpha alpha alpha/alpha alpha alpha). Conclusion: The excess alpha-globin gene/genes cause increment in beta/alpha chain imbalance and leads to worsening pathophysiology and clinical severity of beta-thalassemia carriers.