Heterozygosity of the Complex Corfu δ0β+ Thalassemic Allele (HBD Deletion and HBB:c.92+5G>A) Revisited

Simple Summary The Corfu delta(0)beta(+) thalassemic allele, a unique thalassemic allele combining a deletion of the delta-globin (HBD) and a single nucleotide variant in the beta-globin gene (HBB) in cis has, so far, been described only in individuals of Greek origin. The heterozygosity of Corfu delta(0)beta(+) is detected in 1-2% of the beta-thalassemia carrier population and presents a distinct hematological phenotype of microcytic, hypochromic anemia with normal HbA(2) and elevated HbF levels. The study of the Corfu delta(0)beta(+) allele is important for genotype resolution, genetic counseling and prenatal/antenatal diagnosis, and the management of patients. The Corfu delta(0)beta(+) thalassemic allele is a unique thalassemic allele consisting of the simultaneous presence in cis of a deletion of the delta-globin (Hemoglobin Subunit Delta, HBD) and a single nucleotide variant in the beta-globin gene (Hemoglobin Subunit Beta, HBB). The allele has, so far, been described in individuals of Greek origin. The objectives of the study are to ascertain the prevalence of the Corfu delta(0)beta(+) allele in comparison to other beta-thalassemia variants encountered in Greece using our in-house data repository of 2558 beta-thalassemia heterozygotes, and to evaluate the hematological phenotype of Corfu delta(0)beta(+) heterozygotes in comparison to heterozygotes with the most common beta(+)- and deletion alpha(0)- thalassemia variants in Greece. The results of the study showed a relative incidence of heterozygotes with Corfu delta(0)beta(+) at 1.56% of all beta-thalassemic alleles, and a distinct hematological phenotype of the heterozygotes characterized by microcytic, hypochromic anemia with normal levels of HbA(2) (Hemoglobin A2) and elevated HbF (Hemoglobin F) levels. The application of a specific methodology for the identification of the Corfu delta(0)beta(+) allele is important for precise prenatal and antenatal diagnosis programs in Greece.

Automated summary

The Corfu delta(0)beta(+) thalassemic allele, found only in individuals of Greek origin, is a unique combination of a deletion in the delta-globin gene and a single nucleotide variant in the beta-globin gene. It is detected in 1-2% of beta-thalassemia carriers and presents a distinct hematological phenotype. This study aims to determine the prevalence of the Corfu delta(0)beta(+) allele and evaluate its hematological phenotype compared to other thalassemia variants in Greece.