Updated Molecular Spectrum of β-Thalassemia Mutations in Duhok Province, Northern Iraq: Ethnic Variation and the Impact of Immigration

Abstract

Immigration impact on genetic epidemiology of thalassemia worldwide is well-recognized. Over the past decade, the Duhok Province of Northern Iraq attracted a large number of immigrants. To assess whether immigration had contributed to changes in the mutation spectrum of β-thalassemia (β-thal) in the region, we recruited 218 registered patients with symptomatic β-thal. The recruited patients included 50 (22.9%) from resettled migrant families. A total of 431 β-thal alleles were fully characterized, with 20 different thalassemia mutations, the most frequent being IVS-II-1 (G>A) (HBB: c.315 + 1G>A), IVS-I-6 (T>C) (HBB: c.92 + 6T>C), codon 5 (–CT) (HBB: c.17_18delCT), IVS-I-110 (G>A) (HBB: c.93-21G>A), codon 44 (–C) (HBB: c.135delC), codon 8 (–AA) (HBB: c.25_26delAA) and IVS-I-1 (G>A) (HBB: c.92 + 1G>A) constituting 72.8% of the total. Some differences in mutation spectrum were observed compared to earlier studies from this same province, the most notable of which were the higher frequencies of IVS-I-110 and codon 8. Interestingly, the highest proportions of alleles related to immigrants were encountered in these two allele groups. Ethnic variation was also documented, so that while Muslim Kurds had IVS-II-1, IVS-I-6, IVS-I-110, codon 5 and codon 44 as their most frequent mutations, the most frequent among Kurdish Yazidis, were codon 5, codon 44, codon 8 and IVS-I-6. These ethnic variations and changes in mutation spectrums are important and should be taken in consideration to ensure effective implementation of the thalassemia preventive program.