title: Interaction of an α-Globin Gene Triplication with β-Globin Gene Mutations in Iranian Patients with β-Thalassemia Intermedia.
abstract: The 3.7 kb triplicated α-globin gene (ααα(anti 3.7)) mutation has been found in most populations. It results from an unequal crossover between misaligned homologous segments in the α-globin gene cluster during meiosis. The pathophysiology and clinical severity of β-thalassemia (β-thal) are associated with the degree of α chain imbalance. The excess of α-globin chains plays an important role in the pathophysiology of β-thal. When heterozygous/homozygous β-thal coexists with an α gene numerical alteration, the clinical and hematological phenotype of thalassemia could change to mild anemia in case of an α deletion (-α/αα) or severe anemia in the case of an α triplication (αα/ααα). The coexistence of an ααα(anti 3.7) triplication is considered an important factor in the severity of β-thal, exacerbating the phenotypic severity of β-thal by causing more globin chain imbalance. This study shows that the ααα(anti 3.7) triplication is an important factor in the causation of β-thal intermedia (β-TI) in heterozygous β-thal. This type of phenotype modification has rarely been observed and reported in the Iranian population. Here we report the coinheritance of a triplicated α-globin gene arrangement and heterozygous/homozygous β-thal in 23 cases, presenting with a β-TI or β-thal major (β-TM) phenotype. Some of these patients were considered to have a mild β-TI phenotype as they needed no blood transfusions; some occasionally received blood transfusions in their lifetime (for example on delivery) but some are dependent on regular blood transfusions (every 20 to 40 days). Our study was focused on the importance of detecting the α-globin gene triplication in genotype/phenotype prediction in Iranian thalassemia patients.
authors.affiliation: Kariminejad-Najmabadi Pathology & Genetics Center , Tehran , Iran .
authors.forename: Samaneh
authors.initials: S
authors.lastname: Farashi
authors.forename: Nooshin
authors.initials: N
authors.lastname: Bayat
authors.forename: Negin
authors.initials: N
authors.lastname: Faramarzi Garous
authors.forename: Mehri
authors.initials: M
authors.lastname: Ashki
authors.forename: Mona
authors.initials: M
authors.lastname: Montajabi Niat
authors.forename: Shadi
authors.initials: S
authors.lastname: Vakili
authors.forename: Hashem
authors.initials: H
authors.lastname: Imanian
authors.forename: Sirous
authors.initials: S
authors.lastname: Zeinali
authors.forename: Hossein
authors.initials: H
authors.lastname: Najmabadi
authors.forename: Azita
authors.initials: A
authors.lastname: Azarkeivan
mesh_terms: D000328:Adult; D001803:Blood Transfusion; D004843:Epistasis, Genetic; D004909:Erythrocyte Indices; D005260:Female; D018628:Gene Dosage; D005838:Genotype; D006801:Humans; D007492:Iran; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D055542:alpha-Globins / Q000235:genetics*; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy
chemical_list: D055542:alpha-Globins; D055544:beta-Globins
keywords: blood transfusion(s); αααanti 3.7 Triplication; β-thalassemia intermedia (β-TI); β-thalassemia major (β-TM)