In the 106 samples with Hb A<sub>2</sub> 3.1-3.9%, six had HBB mutations; four Hb Dhonburi [codon 126 (T > G)], one CAP site mutation [CAP + 1 (A > C)] and one beta<sup>0</sup>-thalassemia [codon 41/42 (-TTCT)] with a coinherited HBD mutation [nt-77 (T > C)].
During an intensive screening program aimed at identifying the healthy carriers of thalassemia and the couples at risk of bearing an affected fetus, a rare single nucleotide variation (SNV), CAP + 1570 T > C (HBB:c*96T > C), located 12 nucleotides upstream of the polyadenylation signal in 3'UTR of the beta globin gene was identified.
The mother of the two patients with thalassaemia intermedia was heterozygous for beta-thalassaemia (codon 39 nonsense mutation), while the father had thalassaemia-like red cell indices, an increased alpha/non alpha chain synthesis ratio, a slight increase of HbF and a low HbA2 level, but showed entirely normal beta-globin gene sequences, apart from the complex rearrangement (-T +ATA) at position -530 5' to the CAP site.