Molecular characterization of a novel homozygous deletion in β-globin cluster causing (δβ)0 -Thalassemia among Tunisian family

Abstract Background: Deletions in the β-globin cluster are uncommon and cause thalassemia (thal) with hereditary persistence of fetal hemoglobin (HPFH). They constitute a heterogeneous group of disorders characterized by absent or reduced synthesis of adult hemoglobin (Hb A) and increased synthesis of fetal hemoglobin (Hb F). Although, the clinical severity of these disorders are asymptomatic owing to the increased Hb F levels, the molecular basis is very heterogeneous due to the large deletions in the β-globin cluster spanning both HBD and HBB genes. Here, we describe a Tunisian family carrying a novel deletion mutation causing (δβ)°-thalassemia. Methods: The amounts of hemoglobin fractions were measured by capillary electrophoresis of hemoglobin. Amplification and sequencing of different regions on the β-gene cluster were performed by Sanger method. Results: Family study and genetic analysis revealed a large deletion mutation in the β-globin cluster of 14.5 kb (NG_000007.3:g. 58253 to g.72837del14584) at the homozygous state in the patient and at heterozygous state at the other members of the family. This deletion removes the HBD and HBB genes. Conclusions: In our knowledge, this new large deletion is described for the first time in the Tunisian population and in the world, designed Tunisian(δβ)0 in Ithanet database (IthaID: 3971). Therefore, it is important to identify the deletion leading to δβ-thalassemia carriers at the molecular level, to highlight the importance of recognizing the clinical features and implementing appropriate testing to clarify the diagnosis and manage the condition.