Dominant β-thalassaemia with unusually high Hb A₂and Hb F caused by β^CD121(−G)(HBB:c.364delG) in exon 3 of β-globin gene

Abstract

We describe a dominant β-thalassaemia caused by a deletion of G at nucleotide position 364 in exon 3 of the β-globin gene. The heterozygosity of this mutation was found in a 36-year-old Thai patient who had moderate hypochromic microcytic anaemia with haemolytic blood picture. Haemoglobin (Hb) analysis revealed relatively higher Hbs A2 (6.8%) and F (4.7%) as compared with those of β0-thalassaemia (n=278) and β+-thalassaemia (n=55) carriers in our series. Secondary structure prediction of the elongated β-globin chain showed that the α-helix at the C-terminal is disrupted dramatically by the random coil and β-sheet, which should result in a highly unstable β-globin variant, undetectable in peripheral blood and a dominant clinical phenotypic feature.

De novo HBB frameshift mutation in a patient with dominant β‐thalassemia major

“…The PCR-STR results verified the identity of the proband's biological parents, indicating that the novel mutation had occurred possible de novo in the To further demonstrate the effect of the novel mutation in the HBB gene, we selected HBB:c.364delG and HBB:c.408delT as positive control since they have been reported to cause different degree of anemia and related to unstable elongated β-globin formation, leading to dominant β-thalassemia. 6,7 We constructed a wild-type and three mutant versions of (HBB:c.399delA, HBB:c. and HBB:c.364delG. 3 These mutations can alter the DNA sequence resulting in changes in important functional amino acids, which can in turn affect the tertiary structure of the β-globin chains and the quaternary structure of the Hb tetramer.…”