Molecular Characterization of β-Thalassemia Intermedia in Southeast Iran

Abstract

Inheritance of mild mutations within the β-globin gene and coinheritance of α-thalassemia (α-thal) are known as two important genetic modifiers in β-thalassemia (β-thal) intermedia (β-TI). We aimed to evaluate the spectrum of β- and α-thal mutations in β-TI patients in Southeast Iran. Common β- and α-globin gene mutations were detected by amplification refractory mutation system–polymerase chain reaction (ARMS–PCR) and multiplex gap-PCR, respectively. There were 26 male (57.8%) and 19 female (42.2%) patients. HBB: c.92 + 5T > C [IVS-I-5 (G > C)] and HBB: c.−138C + 1G > A [IVS-II-I (G > A)] represented the prevalent alleles with respective frequencies of 60.0 and 10.0%. Other β-globin mutations included HBB: c.-138C > T [–88 (C > T)], HBB: c.27_28insG [frameshift codons (FSC) 8/9 (+G)], HBB: c.46delT [codon 15 (–T)], HBB: c.93-22_95del (IVS-I, 25 del), and the 619 bp deletion (NG_000007.3: g.71609_72227del619). The predominant genotypic combinations were β⁰/β⁰ (68.9%), β⁰/β⁺(8.9%) and β⁺/β⁺(2.2%). Coinheritance of α-thal was observed in 33.0% of the patients, with the –α^3.7 (rightward) (NG_000006.1: g.34164_37967del3804) as the most common deletion (86.0%). One patient was diagnosed with the –α^4.2 (leftward) (AF221717) and one with the – –^MED (g.24664_41064del16401) deletions, while no patients carried the –(α)^20.5 (g.15164_37864del22701), α^–5 nt (HBA2: c.95 + 2_95_6delTGAGG) or codon 19 (–G) (HBA2: c.56delG) mutations. The alleviating molecular mechanism was not explainable by β⁺or concurrent α-thal in more than half of our β-TI patients. This encourages conducting more studies to identify other contributing factors, especially Hb F-inducing genetic modifiers.

• α-thalassemia (α-thal)
• β-thalassemia intermedia (β-TI)
• mutation(s)

Acknowledgements

The authors would like to thank the patients and their parents who kindly participated in this study. We would also like to thank the personnel of the Prenatal Diagnosis Laboratory, Thalassemia Center, Zahedan City, Iran, especially the laboratory supervisor, Mrs. Roqayeh Javadi, for her technical assistance in achieving the goals of this project.

Declaration of interest

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