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 –α3.7 (rightward) (NG_000006.1: g.34164_37967del3804) as the most common deletion (86.0%). One patient was diagnosed with the –α4.2 (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.