Molecular Characterization of β-Thalassemia in the Dohuk Region of Iraq

Abstract

beta-Thalassemia (thal) is an important health problem in the Dohuk region of northern Iraq because of its high carrier rate and the frequency of consanguineous marriages. Thus, the need to establish an effective preventative program is paramount. As part of this effort, we initiated this study to determine the molecular basis of this disorder in the region. For the latter purpose, either parent of 104 registered beta-thal major/intermedia patients had their full blood counts, hemoglobin (Hb) electrophoresis, Hb A2 and Hb F quantitation performed. Their DNA was extracted, amplified and reverse hybridized to specific oligonucleotide probes to detect 20 beta-thal mutations. The testing detected 12 beta-thalassemic mutations. The eight most frequent were: IVS-II-1 (G-->A), codon 44 (-C), codon 5 (-CT), IVS-I-1 (G-->A), codon 39 (C-->T), IVS-I-6 (T-->C), codons 8/9 (+G) and IVS-I-5 (G-->C). These mutations accounted for 81.7% of the thalassemic defects in the studied individuals. The less frequent mutations were: codon 8 (-AA), IVS-I-110 (G-->A), codon 30 (G-->C) and codon 22 (-7 bp), and the beta-thalassemic defects remained uncharacterized in 11.5% of cases. This is the first study of beta-thal mutations from Iraq, and shows a frequency of thalassemic defects different from those reported in surrounding countries. It provides a foundation for prenatal genetic testing that will be part of a thalassemia prevention program in the Dohuk region.

β-Thalassemia Mutations in the Kurdish Population of Northeastern Iraq

“…This mutation is the most common β-thal mutation in many eastern Mediterranean populations, including Turkey, Lebanon, Jordan and Syria (12)(13)(14)(15)(16), and has its highest frequencies in Cyprus, but its frequency gradually decreases in countries further to the east, with a distribution pattern almost opposite to that of IVS-II-1 (15)(16)(17)(18)(19)(20). However, such a high frequency in Kurds of northeastern Iraq is not shared by those from Dohuk or Iran with frequencies of 1.9 and 6.0%, respectively, but is comparable with those reported from northwestern Iranian populations (18.0%) (8)(9)(10).…”

“…Northeastern Sulaimaniyah Province borders western and northwestern provinces in Iran, and therefore, it is not unexpected that the IVS-II-1 mutation is the most frequent mutation identified in our patients, since it is also the predominant mutation among Iranian Kurds and northwestern Iranians ( Table 2) as well as most other parts of Iran (7)(8)(9). Furthermore, IVS-II-1 was found to be the predominant mutation in Kurds of Dohuk in northern Iraq bordering Turkey (10). However, such high rates are shared neither by Kurdish Jews (11), the population of Diyarbakir in southern Turkey (who are mainly ethnic Kurds as well), nor by the population of East Anatolia in southeastern Turkey where the frequency is even less (12,13).…”

“…Codons 8/9, an Asian Indian β 0 mutation, was the next most prevalent mutation, which is common in the Indian subcontinent (21) as well as Iranian Kurds and northwestern Iranians (15.7 and 14.5% respectively) (8,9). A decreasing frequency was seen as we moved west and north to Dohuk Province (7.7%) and the East Anatolia region of Turkey (5.1%) (10,13). The mutation is less common, sporadic or absent in other surrounding eastern Mediterranean countries (14)(15)(16)(17)(18)20).…”

Presence of the IVS-I-6-Mutated Allele in Beta-Thalassemia Major Patients Correlates with Extramedullary Hematopoiesis Incidence

“…The IVS-I-6 (T→C) mutation is one of the most common causes of β-thalassemia among individuals of Mediterranean and Middle Eastern ancestry [39,40]. Its high incidence has been reported among populations from Portugal [41]; Spain [42,43]; Albania [44]; the region of former Yugoslavia [45,46,47,48]; Greece [49,50,51,52]; Algeria [53]; Egypt [54]; Palestine [55,56]; Lebanon [57]; Syria [58,59]; Cyprus [60]; Turkey [61,62,63,64,65]; Saudi Arabia [66,67]; Iraq [68,69,70,71]; Iran [72,73,74]; and elsewhere. It results from a base substitution close to the 5′ splice junction, between exon I and intron I, and within a conserved consensus sequence, interfering with mRNA splicing and, consequently, reducing its efficiency.…”

Premarital Screening for Hemoglobinopathies: Experience of a Single Center in Kurdistan, Iraq

“…Among the other service indicators for prevention, it was estimated that 5/1,000 couples would be at risk of having affected children with major hemoglobinopathies, with an estimated annual birth rate of 39 affected children [5]. Other studies revealed that 8 different β-thal mutations are responsible for the large majority of cases [10,11]. Service indicators for patients' care, on the other hand, showed a total number of 845 registered patients with major hemoglobinopathies at the thal care center.…”