Molecular Spectrum of β-Thalassemia Mutations in Northwestern Iran

Abstract

Beta-thalassemia (beta-thal) is a hereditary autosomal disorder with decreased or absent beta-globin chain synthesis. This study was designed to identify the common and rare beta-thal mutations in the Azerbaijan provinces, Northwestern Iran, and to set up a prenatal diagnostic laboratory. One hundred unrelated patients with known beta-thal major and intermedia, registered with the thalassemia clinics in the provincial capitals of Tabriz and Ardebil, were included. Mutations were studied in 200 chromosomes, by polymerase chain reaction-amplification refractory mutation system (PCR-ARMS) and direct sequencing methods. We found 17 beta-thal mutations in this region of Iran. The results showed that IVS-II-1 (-->GA) was the most frequent mutation, comprising 21% of all mutations. Other common mutations were IVS-I-110 (-->GA) 18%, frameshift codons (FSC) 8/9 (+G) 14.5%, FSC 8 (-AA) 8% and IVS-I-1 (GA) 7.5%. This is the first comprehensive study in this region and could be useful for developing a beta-thal molecular screening in Azerbaijan-Iran.

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).…”

“…The tribal and social connections between Kurds throughout this large area spans more than two thousand years and well before the establishment of modern boundaries between the latter countries (6). 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).…”

“…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).…”

Homozygosity for a Rare β0-Thalassemia Mutation [Frameshift Codons 25/26 (+T)] Causes β-Thalassemia Intermedia in an Iranian Family

“…Our study is important in some respects: firstly, this family, also mentioned by Hosseinpour Feizi et al (8), is the first report of this mutation in Iran. Therefore, it is necessary to include this sequence alteration in the molecular screening of at-risk couples.…”

“…We previously reported this mutation as an independent allele in a molecular screening study in Azerbaijan Province in Iran (8) and are now reporting data for the whole family. The phenotype of the mutation is as expected for a β 0 -thal trait.…”