Moosavi Azam, Ardekani Ali M
Department of Biochemistry, Faculty of Medicine, Alborz University of Medical Sciences, Alborz, Iran.
Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
Avicenna J Med Biotechnol. 2017 Oct-Dec;9(4):196-200.
β-thalassemia is the most common monogenic disorder in Iran, and one of the challenges in the screening of the carriers is the coinheritance of α-thalassemia mutations. In the view of high prevalence of α-thalassemia mutations in many parts of the country, the aim of this study was to determine the carrier frequency of common alpha deletions, as a secondary modifier in clinical manifestations of beta thalassemia, in known beta-thalassemia carriers and some hematology parameter changes.
The study included families referred from different primary health care centers with microcytic hypochromic anemia [MCV<80fl; MCH<27 ] and A2>3.4%]. Genomic DNA was extracted from peripheral blood leukocytes by salting out method. For common β-globin gene mutation analysis, amplification refractory mutation system- polymerase chain reaction (ARMS-PCR) and for rare β-thal alleles, DNA sequencing were used. Also, for investigation of common α-globin gene cluster deletions (-α3.7, -α4.2, --MED and -α20.5), multiplex Gap-PCR was performed.
Among 227 β-thalassemia minor individuals studied, α-globin gene deletions were found in 43 cases: 37 heterozygote -α3.7 (16.3%), 5 homo -α3.7 (2.2%) and 1 --MED (0.44%). Also, the co-inheritance of α-globin gene deletion and triplication was not found in the studied individuals.
Although it is highly recommended that physicians and genetic counselors involved in the screening program of beta-thal major in the country consider this phenomenon because of high prevalence of this coinheritance, hematologic indices changes are very slight.
β地中海贫血是伊朗最常见的单基因疾病，携带者筛查面临的挑战之一是α地中海贫血突变的共遗传。鉴于该国许多地区α地中海贫血突变的高患病率，本研究的目的是确定已知β地中海贫血携带者中常见α缺失的携带者频率，作为β地中海贫血临床表现的次要修饰因素，以及一些血液学参数的变化。
该研究纳入了来自不同初级卫生保健中心的家庭，这些家庭患有小细胞低色素性贫血[平均红细胞体积（MCV）<80fl；平均红细胞血红蛋白含量（MCH）<27pg；血红蛋白A2（HbA2）>3.4%]。采用盐析法从外周血白细胞中提取基因组DNA。对于常见的β珠蛋白基因突变分析，使用扩增阻滞突变系统-聚合酶链反应（ARMS-PCR），对于罕见的β地中海贫血等位基因，使用DNA测序。此外，为了研究常见的α珠蛋白基因簇缺失（-α3.7、-α4.2、--MED和-α20.5），进行多重缺口PCR。
在研究的227例轻型β地中海贫血个体中，发现43例存在α珠蛋白基因缺失：37例为杂合子-α3.7（16.3%），5例为纯合子-α3.7（2.2%），1例为--MED（0.44%）。此外，在所研究的个体中未发现α珠蛋白基因缺失与三倍体的共遗传。
尽管强烈建议该国参与重型β地中海贫血筛查项目的医生和遗传咨询师考虑这种共遗传现象的高患病率，但血液学指标变化非常轻微。
