Soler Ana María, Piellusch Bruna Facanali, Silveira Lorena da, Pedroso Gisele Audrei, López Pablo, Savio Enrique, Sonati María de Fatima, Luz Julio da
Universidad de la República (UdelaR), Centro Universitario Regional (CENUR) Litoral Norte, Departamento de Ciencias Biológicas, Laboratorio de Genética Molecular Humana, Salto, Uruguay.
Universidade Estadual de Campinas (UNICAMP), Faculdade de Ciências Médicas, Departamento de Patología Clínica, Campinas, SP, Brazil.
Genet Mol Biol. 2021 Mar 26;44(2):e20200399. doi: 10.1590/1678-4685-GMB-2020-0399. eCollection 2021.
Alpha thalassemia is the most common genetic disorder across the world, being the α-3.7 deletion the most frequent mutation. In order to analyze the spectrum and origin of alpha thalassemia mutations in Uruguay, we obtained a sample of 168 unrelated outpatients with normal hemoglobin levels with microcytosis and hypochromia from two cities: Montevideo and Salto. The presence of α-thalassemia mutations was investigated by gap-PCR, restriction endonucleases analysis and HBA2 and HBA1 genes sequencing, whereas the alpha-MRE haplotypes were investigated by sequencing. We found 55 individuals (32.7%) with α-thalassemia mutations, 51(30.4%) carrying the -α3.7 deletion, one with the -α4.2 deletion and three having the rare punctual mutation HBA2:c.-59C>T. Regarding alpha-MRE analysis, we observed a significant higher frequency of haplotype D, characteristic of African populations, in the sample with the -α3.7 deletion. These results show that α-thalassemia mutations are an important determinant of microcytosis and hypochromia in Uruguayan patients with microcytosis and hypochromia without anemia, mainly due to the -α3.7 deletion. The alpha-MRE haplotypes and the α-thalassemia mutations spectrum suggest a predominant, but not exclusive, African origin of these mutations in Uruguay.
α地中海贫血是全球最常见的遗传性疾病，α-3.7缺失是最常见的突变类型。为了分析乌拉圭α地中海贫血突变的谱系和起源，我们从蒙得维的亚和萨尔托这两个城市选取了168名血红蛋白水平正常但有小红细胞症和低色素血症的非亲属门诊患者作为样本。通过缺口PCR、限制性内切酶分析以及HBA2和HBA1基因测序来研究α地中海贫血突变的存在情况，而通过测序来研究α-MRE单倍型。我们发现55名个体（32.7%）存在α地中海贫血突变，51名（30.4%）携带-α3.7缺失，1名携带-α4.2缺失，3名具有罕见的点突变HBA2:c.-59C>T。关于α-MRE分析，我们观察到在携带-α3.7缺失的样本中，具有非洲人群特征的单倍型D的频率显著更高。这些结果表明，α地中海贫血突变是乌拉圭无贫血的小红细胞症和低色素血症患者小红细胞症和低色素血症的重要决定因素，主要是由于-α3.7缺失。α-MRE单倍型和α地中海贫血突变谱系表明，在乌拉圭，这些突变主要但并非唯一地起源于非洲。
