Molecular Basis of β-Thalassemia Intermedia in Erbil Province of Iraqi Kurdistan

Abstract

β-Thalassemia intermedia (β-TI) is a clinical term describing a range of clinical phenotypes that are intermediate in severity between the carrier state and β-thalassemia major (β-TM). To characterize the molecular basis of β-TI in Erbil Province, Northern Iraq, 83 unrelated patients were investigated. Detection of β-globin gene mutations was carried out by reverse hybridization assay and direct gene sequencing. All patients were screened for the XmnI polymorphism by direct sequencing of HBG2 (Gγ promoter gene). Detection of α-globin gene deletions and triplication was carried out using the reverse hybridization assay. Four main molecular patterns were identified in association with the β-TI phenotype, namely: β+/β+ (38.5%), β+/β0 (21.6%), β0/β0 (31.3%), and β0/wild type (8.4%). IVS-I-6 (T > C) was the most frequently encountered mutation (55 alleles, 34.6%), followed by IVS-II-1 (G > A) and codon 8 (−AA); furthermore, we report for the first time from Iraq two β+ mutations, −87 (C > G) and 5′ untranslated region (5′UTR) +22 (G > A). The XmnI polymorphism was detected in 47.0% of patients, mainly in association with the β0/β0 genotype. The α-globin gene deletions were encountered in four cases, including one case with (– –FIL) double gene deletion, a report that is the first from our country. The α-globin gene triplication was detected in five of the seven heterozygous β-thalassemia (β-thal) patients. Similar to other Mediterranean countries, inheritance of mild β-globin mutations was the main molecular pattern underlying β-TI in our patients followed by the ameliorating effect of the XmnI polymorphism.