NEW AND KNOWN beta-THALASSEMIA DETERMINANTS MASKED BY KNOWN AND NEW delta GENE DEFECTS [Hb A(2)-Ramallah OR delta 6(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 beta-globin gene (HBBc.28_29ins TA 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 beta-thalassemia (beta-thal), trait with high RBC counts and compensated mild microcytic anemia. However, the Hb A(2) level was reported to be normal due to the presence of the common Hb A(2)' or Hb B2 [delta 16(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 beta-globin gene defect [codon 6 (-A), HBB:c.20delA] in combination with a novel delta-globin gene defect at codon 6 [HBD.c.19G>C, Glu6Gln] that we have named Hb A(2)-Ramallah. In both cases, the provisional diagnosis could have been compromised when based on the measurement of the normal Hb A(2) fraction only.