Molecular Characterization of β- and α-Globin Gene Mutations in Individuals with Borderline Hb A₂ Levels

Abstract

Elevated Hb A₂ level (≥4.0%) is considered to be reliable parameter to identify β-thalassemia (β-thal) carriers. However, some β-thal carriers have been misdiagnosed as their Hb A₂ levels are below 4.0%. In addition, coinheritance of α-thalassemia (α-thal) and β-thal might affect Hb A₂ levels. Therefore, the aim of this study was to investigate the mutations of β- and α-globin genes in individuals with borderline Hb A₂ levels in Thailand. Three hundred samples from individuals with Hb A₂ levels of 3.5–3.9% were collected for molecular diagnosis of β-globin gene mutations. In addition, the α⁰-thal, α⁺-thal, Hb Constant Spring (Hb CS, HBA2: c.427T>C), and Hb Paksé (HBA2: c.429A>T) diagnostics were also performed. Sixteen samples (5.33%) had β-globin gene mutations, and codon 41/42 (–TTCT) (HBB: c.126_129delCTTT) was the most prevalent mutation. Ninety-eight samples (32.67%) had α-globin gene mutations including four Hb H (β4)-Hb CS disease, two Hb H disease, 13 heterozygous α⁰-thal, 11 homozygous α⁺-thal, two α⁺-thal/Hb CS, one α⁺-thal/Hb Paksé, 61 heterozygous α⁺-thal, and four Hb CS. Furthermore, seven cases of β-thal carriers coinheriting α-thal were observed, and five of them carried Hb H disease. High prevalence of both α- and β-thal in subjects with borderline Hb A₂ levels suggested that molecular diagnosis of α- and β-thal should be performed, especially in a high prevalence area of thalasssemia carriers, for accurate diagnosis and genetic counseling to prevent and control new severe thalassemia cases. Moreover, β-thal carriers who coinherited Hb H disease might have reduced Hb A₂ levels, leading to a misdiagnosis of β-thal in analysis programs.

Keywords:

• α-Thalassemia (α-thal)
• β-thalassemia (β-thal)
• borderline Hb A2
• coinheritance
• molecular characterization

Acknowledgments

We would like to thank the technicians at the Associated Medical Sciences Clinical Service Center (AMS-CSC), Chiang Mai University, Chiang Mai, Thailand for their assistance. The authors thank Mrs. Kallayanee Treesuwan and Dr. Panthong Singboottra Myers, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand, for refinement of the English language.

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, Phayao, Thailand [Grant No. AHS-RD-62001].