The Spectrum of δ-Thalassemia in the Western Sicily.
Authors: Maggio Aurelio , Passarello Cristina , Ruggeri Gaetano , Teresi Pietro , Anzà Maurizio , Meo Anna , Giambona Antonino 
Published: April 2020

Abstract
The detection of β-thalassemia carriers is based on the correct estimation of HbA2 values.The diagnosis of β-thalassemia carriers may be more complicated in presence of δ-thalassemia because the interaction between δ and β-globin gene defects modifies the HbA2 values. For this reason, we studied the spectrum of δ-globin gene mutations present in the Sicilian population, characterized by its very high heterogeneity in β-thalassemia genotype and phenotype. The samples were selected by screening and routine prenatal diagnoses counseling for thalassemia. Among 7153 samples studied for β-thalassemia, 205 samples were selected for HbA2 levels ranging from 0.5% to 2.0% and normal haematology parameters, suspected of being δ-thal carriers in the absence of α and β-thalassemia or hemoglobin variants, and for HbA2 levels from 2.1% to 4.6% in subjects suspected of compound heterozygotes for δ and β-thalassemia and between 1.4% and 2.0% for δ and α-thalassemia. We have considered the value of 2% as the treshold between normal and d-carrier subjects. One-hundred-eighty-three samples showed to be positive for δ-globin gene mutations.Twelve mutations were detected and among these five were new δ-globin gene defects (HbA2-Catania, HbA2-Corleone, HbA2-Ventimiglia; HbA2-Montechiaro and HbA2-Bagheria) determining δ-globin gene variants and seven were already described mutations. Among these six of them were point mutations (HbA2-Mitsero, HbA2-NYU,HbA2-Yialousa, HbA2-Coburg, HbA2-Fitzroy) and one a 7.2 Kb deletion mutation known as the δ-Corfù type, HBD g.5946_1262del. As it was previously shown in Sicily for β-thalassemia, only three mutations account for 91% (HbA2-Yialousa, HbA2-NYU, IVS II-3′ A→G) of the overall δ-globin gene defects. HbA2-Yialousa (g.82G→T) is the most common mutation found in Sicilian population (81%) while the other eleven mutations are less frequent between 0.5 to 5.5%. These findings suggest that in Sicily δ-thalassemia is very common (2.5%) and as it was described, previously, for the β-thalassemia mutations,this also is very heterogeneous (twelve mutations). This information is noteworthy considering the implication that the interaction between β and δ-thalassemia could determine in terms of HbA2 decrease in subjects heterozygotes for β-thalassemia.
HbA2 levels in δ-thalassemia and δ globin gene variants with and without interaction with α or β-globin gene mutations. The δ-alleles are all in heterozygote state except three cases with homozygosis. βA/βA αα/αα Gγ-158/Gγ 1.1 1 βA/βA αα/αα 1.7±0.2 113 βA/βA αα/αα 2.1±0.1 4 βA/βA αα/αα 0.7±0.1 3 βA/β(IVS1,110) αα/αα 3.35±0.15 2 βA/β(cd39) αα/αα 3.5 1 Hb A2-Yialousa βA/β(IVS1,1) αα/αα 3.5 1 βA/β(−87G) αα/αα 4.6 1 βA/β(−101) αα/αα 2.8 1 βA/β(IVS1,6) αα/αα 3.0±0.2 4 βA/βS αα/αα 2.7±0.1 5 βA/βA α−3.7α/αα 1.8±0.2 5 βA/βA α−20.5α/αα 1.4±0.1 2 βA/βA α−Medα/αα 1.6±0.1 2 βA/βA αNcoIα/αα 1.7±0.2 2 βA/βA αHphIα/αα 1.7±0.2 2 Hb A2-NYU βA/βA αα/αα 1.5±0.2 9 βA/β(Valletta) α−3.7α/αα 1.6 1 Hb A2-Mitsero βA/βA αα/αα 1.9±0.2 3 βA/βA α−3.7α/αα 1.6 1 Hb A2-Coburg βA/βA αα/αα 1 1 Hb A2-Fitzroy βA/βA αα/αα 1.4±0.2 3 Hb A2-Catania βA/βA αα/αα 1.2 1 Hb A2-Corleone βA/βA αα/αα 1.6 1 Hb A2-Ventimiglia βA/βA αα/αα 2 1 Hb A2-Montechiaro βA/βA αα/αα 1.3 1 Hb A2-Bagheria βA/βA αα/αα 1.7 1 7.2 Kb deletion βA/βA αα/αα 1.4±0.1 3 βA/βA αα/αα 1.5±0.2 4 IVS II-3′ βA/β(IVS1,110) αα/αα 3.3±0.2 3 βA/β αα/ααα 2.5 1 GENOTYPE δ GENOTYPEβ GENOTYPEα GENOTYPEγ HbA2% N° OF δ CARRIERS