Compound Heterozygote for a Novel Elongated C-Terminal β-Globin Variant (HBB: c.364delG) and Hb E (HBB: c.79G>A) with Heterozygous α-Thalassemia-2

Abstract

This study reports the case of 2-year-old Northeastern Thai girl with β-thalassemia (β-thal) disease who has required regular blood transfusions since she was 8 months old. Hemoglobin (Hb) analysis by high performance liquid chromatography (HPLC) separated Hb A₂/E (16.5%), Hb F (22.7%), Hb A (51.8%) and an abnormal peak (Hb X) found at a retention time (RT) of 5.05 min. (C-window) with 2.8%. Multiplex gap-polymerase chain reaction (gap-PCR) revealed heterozygous α-thalassemia-2 (α-thal-2) (–α^3.7/αα; NG_000006.1: g.34164_37967 del3804). This patient was suspected of having a β-globin chain variant and Hb E (HBB: c.79G>A) according to the high Hb F level and disease presentations. Surprisingly, Hb Mahasarakham (the geographic origin of the proband), a novel single nucleotide deletion (–G) at the first nucleotide of codon 121 (HBB: c.364delG), was identified by direct DNA sequencing and secondary confirmation by PCR-restriction fragment length polymorphism (PCR-RFLP). This novel mutation causes a frameshift mutation and added 10 more residues to the β-globin chain that was elongated to 156 amino acids. Molecular basis of this novel mutation in the heterozygous state is required to confirm the mode of inheritance.

Keywords:

• α-Thalassemia-2 (α-thal-2)
• Hb E
• novel elongated C-terminal β-globin variant
• Thai population

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 funded by a grant from the Thailand Research Fund [MRG5580069].