Heterozygosity of the Complex Corfu δ(0)β(+) Thalassemic Allele (HBD Deletion and HBB:c.92+5G>A) Revisited

SIMPLE SUMMARY: The Corfu δ(0)β(+) thalassemic allele, a unique thalassemic allele combining a deletion of the δ-globin (HBD) and a single nucleotide variant in the β-globin gene (HBB) in cis has, so far, been described only in individuals of Greek origin. The heterozygosity of Corfu δ(0)β(+) is detected in 1–2% of the β-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 δ(0)β(+) allele is important for genotype resolution, genetic counseling and prenatal/antenatal diagnosis, and the management of patients. ABSTRACT: The Corfu δ(0)β(+) thalassemic allele is a unique thalassemic allele consisting of the simultaneous presence in cis of a deletion of the δ-globin (Hemoglobin Subunit Delta, HBD) and a single nucleotide variant in the β-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 δ(0)β(+) allele in comparison to other β-thalassemia variants encountered in Greece using our in-house data repository of 2558 β-thalassemia heterozygotes, and to evaluate the hematological phenotype of Corfu δ(0)β(+) heterozygotes in comparison to heterozygotes with the most common β(+)- and deletion α(0)- thalassemia variants in Greece. The results of the study showed a relative incidence of heterozygotes with Corfu δ(0)β(+) at 1.56% of all β-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 δ(0)β(+) allele is important for precise prenatal and antenatal diagnosis programs in Greece.