Abstract

Inheritance of mild mutations within the -globin gene and coinheritance of -thalassemia (-thal) are known as two important genetic modifiers in -thalassemia (-thal) intermedia (-TI). We aimed to evaluate the spectrum of - and -thal mutations in -TI patients in Southeast Iran. Common - and -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 -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 619bp deletion (NG_000007.3: g.71609_72227del619). The predominant genotypic combinations were (0)/(0) (68.9%), (0)/(+)(8.9%) and (+)/(+)(2.2%). Coinheritance of -thal was observed in 33.0% of the patients, with the -(3.7) (rightward) (NG_000006.1: g.34164_37967del3804) as the most common deletion (86.0%). One patient was diagnosed with the -(4.2) (leftward) (AF221717) and one with the - -(MED) (g.24664_41064del16401) deletions, while no patients carried the -()(20.5) (g.15164_37864del22701), (-5nt) (HBA2: c.95+2_95_6delTGAGG) or codon 19 (-G) (HBA2: c.56delG) mutations. The alleviating molecular mechanism was not explainable by (+)or concurrent -thal in more than half of our -TI patients. This encourages conducting more studies to identify other contributing factors, especially Hb F-inducing genetic modifiers.