Molecular Characterization and Hematological Aspects of Hb E-Myanmar [β26(B8)Glu→Lys and β65(E9)Lys→Asn, HBB: c.[79G>A;198G>C]): A Novel β-Thalassemic Hemoglobin Variant

Abstract

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) [–α^3.7 (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;
• Hb E-Myanmar;
• β-thalassemia (β-thal);
• high performance liquid chromatography (HPLC)

Acknowledgements

We would like to thank the technicians at Maesot Hospital, Tak, Thailand for their assistance.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This study was supported by the School of Allied Health Sciences, University of Phayao, Phayo, Thailand [Grant No. AHS-RD-61001].