Heterozygous β‐thalassemia: Relationship between the hematological phenotype and the type of β‐thalassemia mutation

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Abstract
In this study we have correlated the severity of the hematological features to the type of the β‐thalassemia mutation [codon 39 (C→T), IVS‐I nt 110 (G→A), IVS‐I nt 1 (G→A), IVS‐I nt 6 (T→C), IVS‐II nt 745 (C→G), −87 (C→G) and β6 (‐1bp)], in a group of β‐thalassemia heterozygotes of Italian descent in whom we excluded the presence of iron deficiency or deletion α‐thalassemia. The β‐thalassemia mutation was defined by dot blot analysis on amplified DNA with allelic specific oligonucleotide probes. We found that (a) heterozygotes for β+ IVS‐I nt 6 and β+ ‐ 87 mutations produce larger and better hemoglobinized red blood cells, and )b) heterozygotes for β+IVS‐I nt 6 and β+IVS‐I nt 110 mutations have a less marked increase of Hb A2 levels as compared to heterozygotes for the other mutations investigated. These findings indicate that milder β‐thalassemia mutations such as the β+IVS‐I nt 6 and β+ ‐ 87, express also in the heterozygous state a milder phenotype as compared to β°+‐thalassemia or severe β+ thalassemia (β+IVS‐I, nt 110. The Hb A2 levels, on the other hand, were not related to the severity of the mutation because of less marked increase was found in a mild (β+IVS‐I nt 6) as well in a severe (β+IVS‐I nt 110) mutation. From the practical point of view these findings should be adequately considered in carrier screening and genetic counselling.