New and Known β-Thalassemia Determinants Masked by Known and New δ Gene Defects [Hb A₂-Ramallah or δ6(A3)Glu→Gln, GAG>>CAG]

Abstract

We report a novel thalassemia determinant found in a Nigerian woman living in the Netherlands, resulting from a 2 bp insertion at codons 9/10 of the β-globin gene (HBBc.28_29insTA p.Ser10LeufsX11). The novel defect causes a frameshift with a consequent premature TGA stop codon, located at 11 positions downstream from the mutated codon. The phenotype was typical of a β-thalassemia (β-thal), trait with high RBC counts and compensated mild microcytic anemia. However, the Hb A₂ level was reported to be normal due to the presence of the common Hb A₂' or Hb B2 [δ16(A13)Gly→Arg, GGC>CGC] variant that was not taken into account. We also present the opposite but comparable situation found in an a Palestinian man living in the USA. He was a carrier of a common β-globin gene defect [codon 6 (–A), HBB:c.20delA] in combination with a novel δ-globin gene defect at codon 6 [HBD. c.19G>C, Glu6Gln] that we have named Hb A₂-Ramallah. In both cases, the provisional diagnosis could have been compromised when based on the measurement of the normal Hb A₂ fraction only.

• Thalassemia mutations
• Hb A₂-Ramallah [δ6(A3)Glu→Gln
• GAG>CAG](?)