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

Abstract

Background: Copy number variations in α-globin genes are results of unequal crossover between homologous segments in the α-globin gene cluster that misalign during the meiosis phase of the gametogenesis process. Reduction or augmentation of α-globin genes leads to imbalance of α/β chains in hemoglobin tetramer and consequently attenuate or worsen the β-thal clinical symptoms, respectively.

Objective: Multiplications in α-globin genes have been found in some populations, justifying unexpected severe phenotype of β-thal carriers.

Study design: Unexpected severe phenotype in the family members may result from coexistence of extra α-globin genes, which is an important factor in the causation of thalassemia intermedia and major in heterozygous β-thalassemia.

Results: We described different multiplications in α-globin locus in an Iranian family with one, two or three extra α-globin genes (ααα/αα, αααα/αα and αααα/ααα).

Conclusion: The excess α-globin gene/genes cause increment in β/α chain imbalance and leads to worsening pathophysiology and clinical severity of β-thalassemia carriers.

Keywords: Iranian; copy number variation; gametogenesis; α-globin gene cluster; β-thalassemia carrier.