Molecular Characterization of β-Thalassemia Intermedia in Southeast Iran.
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 β(0)/β(0) (68.9%), β(0)/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.
a Genetics of Non-Communicable Disease Research Center, Zahedan University of Medical Sciences , Zahedan , Iran.|b Department of Genetics , Faculty of Medicine, Zahedan University of Medical Sciences , Zahedan , Iran.
Ebrahim
E
Miri-Moghaddam
c Department of Biology , Payame Noor University , Zahedan , Iran.
Sara
S
Bahrami
d Genetics of Non-Communicable Disease Research Center, Zahedan University of Medical Sciences , Zahedan , Iran.|e Department of Pediatric Hematology & Oncology , Faculty of Medicine, Zahedan University of Medical Sciences , Zahedan , Iran.
Majid
M
Naderi
f Faculty of Allied Medical Sciences , Zabol University of Medical Sciences , Zabol , Iran.
Ali
A
Bazi
g Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran , Tehran , Iran.
Morteza
M
Karimipoor
D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007492:Iran / Q000453:epidemiology; D008297:Male; D017720:Molecular Epidemiology; D009154:Mutation; D016133:Polymerase Chain Reaction; D055542:alpha-Globins / Q000235:genetics; D017085:alpha-Thalassemia / Q000235:genetics; D055544:beta-Globins / Q000235:genetics; D017086:beta-Thalassemia / Q000453:epidemiology / Q000235:genetics*
D055542:alpha-Globins; D055544:beta-Globins
mutation(s); α-thalassemia (α-thal); β-thalassemia intermedia (β-TI)