Hb E [β26(B8)Glu→Lys, GAG>AAG, HBB: c.79G>A] is an inherited thalassemic β-globin variant that favors the Hb E-β-thalassemia (β-thal) syndrome when interacting with the β-thal gene. However, hemoglobin (Hb) variants carrying Hb E in combination with another variant on the same β gene are rare. We recently studied a 29-year-old pregnant woman, initially diagnosed as a β-thal carrier. Hemoglobin and DNA analysis were performed by high performance liquid chromatography (HPLC) and DNA sequencing. Hematological data revealed no anemia or altered red blood cell (RBC) parameters. Hemoglobin HPLC showed Hb A and Hb A2 but no Hb E or abnormal Hb peaks, with a markedly elevated Hb A2 level (6.4%) reaching the accepted range (4.0-10.0%) for β-thal trait. DNA analysis identified a GAG>AAG transition at codon 26 of the β-globin gene that is responsible for Hb E, and an AAG>AAC mutation at codon 65 in cis on the β-globin chain resulting in a lysine to asparagine substitution. These two mutations led to the formation of a novel variant, namely Hb E-Myanmar, β26(B8)Glu→Lys and β65(E9)Lys→Asn, HBB: c.[79G>A;198G>C]. Moreover, a heterozygous α-thalassemia-2 (α-thal-2) [-α3.7 (rightward)] deletion was also observed. Hb E-Myanmar is a doubly substituted β-globin variant, which has not been previously described. This variant did not have any clinical or hematological abnormalities, and the genetic mechanism resulting in this variant is discussed. The new simultaneous allele-specific polymerase chain reaction (ASPCR) was developed for rapid detection of these two mutations within the same β-globin chain.
Keywords: Hb E-Myanmar;; Hb E;; high performance liquid chromatography (HPLC); β-thalassemia (β-thal);.