A Novel Promoter Mutation (HBB: c.-75G>T) Was Identified as a Cause of β⁺-Thalassemia

Abstract

We report a novel β-globin gene promoter mutation in a Chinese family identified using fluorescence resolution melting curve analysis and gene sequencing. The proband, who showed the phenotype of β-thalassemia intermedia (β-TI), was found to be a compound heterozygote for the novel mutation −25 (G>T) (HBB: c.-75G>T) and a codon 17 (HBB: c.52A>T) mutation. Moreover, conservation analysis using phyloP and phastCons indicated that the mutated base in the proband was conserved. This novel point mutation on the β-globin gene is in close proximity to the conserved ATAA sequence located at position −25 relative to the mRNA Cap site. We performed a further comparative analysis of the clinical phenotypes and hematological parameters in this pedigree and found that the father was a carrier of the novel point mutation and showed low levels of hemoglobin (Hb), mean corpuscular volume (MCV) and mean corpuscular Hb (MCH). Thus, the available evidence suggests that this novel mutation, −25, results in β⁺-thalassemia (β⁺-thal).

• β-Globin gene
• β-thalassemia (β-thal)
• promoter mutation

Acknowledgements

We thank the patients who volunteered to be in this study. We also thank the professional language editing services of Elsevier Web Shop for proofreading the manuscript.

Declaration of interest

This study was supported by National Nature Science Foundation of China, Grants 81400639. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.