Derakhshan Sima M, Khaniani Mahmoud S, Afkhami Fateme, PourFeizi Abbasali H
a Haematology and Oncology Research Centre , Tabriz University of Medical Sciences , Tabriz , Iran.
b Medical Genetic Department, Medical Faculty , Tabriz University of Medical Sciences , Tabriz , Iran.
Hemoglobin. 2016 Sep;40(5):319-322. doi: 10.1080/03630269.2016.1240688.
The aim of this study was to determine the molecular spectrum and frequency of deletional and nondeletional α-thalassemia (α-thal) mutations and the genotype-phenotype correlation in common mutations in the Azeri population of Northwestern Iran. A total of 1256 potential carriers with microcytic and hypochromic anemia and normal Hb A levels (<3.5%) and without iron deficiency anemia plus three fetuses were identified. Multiplex gap-polymerase chain reaction (gap-PCR) and sequencing for α-thal mutations were carried out. In 606 individuals, the α-globin gene was normal, but in 650 persons (51.6%) and three fetuses, 10 different mutations were detected. The most frequent deletional genotypes were as follows: αα/-α (61.7%), -α/-α (11.9%), αα/-α (4.6%), αα/- - (4.3%) and αα/-(α) (3.8%). The most frequent nondeletional genotypes were αα/αα (HBA2: c.95+2_95+6delTGAGG) and αα/αα [polyadenylation signal (polyA2) (AATAAA>AATGAA); HBA2: c.*96G>A] with frequencies of 1.08% and 0.92%, respectively. Meanwhile, 7.71% of individuals with a proven β-thalassemia (β-thal) mutation were found to also carry an α-thal mutation. Persons having two functional α-globin genes showed lower mean corpuscular volume (MCV) and mean corpuscular hemoglobin (Hb) (MCH) values compared to those with one mutated α-globin gene, provided that they had normal β-globin genes. Overall, the incidence of α-thal was 2.7% in the Azeri population in Northwestern Iran. Our results showed that the variability of α-thal mutations are high in the Azeri population and that α-thal mutations are highly heterogeneous in both deletional and nondeletional genotype aspects.
本研究旨在确定伊朗西北部阿塞拜疆人群中缺失型和非缺失型α地中海贫血（α-地贫）突变的分子谱及频率，以及常见突变中的基因型-表型相关性。共鉴定出1256名潜在携带者，他们患有小细胞低色素性贫血，血红蛋白A水平正常（<3.5%）且无缺铁性贫血，另外还有3名胎儿。对α-地贫突变进行了多重缺口聚合酶链反应（gap-PCR）和测序。在606名个体中，α珠蛋白基因正常，但在650人（51.6%）和3名胎儿中检测到10种不同突变。最常见的缺失型基因型如下：αα/-α（61.7%）、-α/-α（11.9%）、αα/-α（4.6%）、αα/--（4.3%）和αα/-(α)（3.8%）。最常见的非缺失型基因型为αα/αα（HBA2：c.95+2_95+6delTGAGG）和αα/αα [聚腺苷酸化信号（polyA2）（AATAAA>AATGAA）；HBA2：c.*96G>A]，频率分别为1.08%和0.92%。同时，发现7.71%经证实携带β地中海贫血（β-地贫）突变的个体也携带α-地贫突变。具有两个功能性α珠蛋白基因的个体，与具有一个突变α珠蛋白基因的个体相比，其平均红细胞体积（MCV）和平均红细胞血红蛋白（Hb）（MCH）值更低，前提是他们的β珠蛋白基因正常。总体而言，伊朗西北部阿塞拜疆人群中α-地贫的发病率为2.7%。我们的结果表明，阿塞拜疆人群中α-地贫突变的变异性很高，并且α-地贫突变在缺失型和非缺失型基因型方面都高度异质。
