Molecular and Hematological Characterization of a Novel Translation Initiation Codon Mutation of the α2-Globin Gene (ATG>ATC or HBA2: c.3G>C)

Abstract

Although mutations causing α-thalassemia (α-thal) are mainly larger deletions involving one or both of the duplicated α-globin genes, point mutations are not rare. We have identified a novel mutation of the translation initiation codon of the α2-globin gene with DNA sequencing and allele-specific multiplex ligation-dependent probe amplification (MLPA) in a Chinese family. RNA analysis was performed with reverse transcription-MLPA (RT-MLPA). A novel mutation at the translation initiation codon of the α2-globin gene (HBA2: c.3G>C) was identified. The proband and his father, who were both carriers of this mutation, had a hematological phenotype of mild α⁺-thalassemia (α⁺-thal) trait with low-normal limit of mean corpuscular volume (MCV) and normal Hb A₂. RNA analysis showed markedly decreased levels of α-globin mRNA and the presence of a small amount of mutant mRNA. The HBA2: c.3G>C mutation most likely caused α-thal by lowering levels of wild α-globin chain. Our study increases the mutation spectrum of α-thal.

Keywords:

• α-Thalassemia (α-thal)
• initiation codon
• novel mutation
• reverse transcription-multiplex ligation-dependent probe amplification (RT-MLPA)

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 Medical Scientific Research Foundation of Guangdong Province [A2019076] and the Social Developmental Project of Dongguan [201950715859136].