Abstract 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.

中文翻译：

---

乌拉圭小红细胞增多症和低色素血症无贫血患者的α地中海贫血和α-MRE单倍型

摘要α地中海贫血是世界上最常见的遗传性疾病，α-3.7缺失是最常见的突变。为了分析乌拉圭α地中海贫血突变的频谱和起源，我们从两个城市：蒙得维的亚和萨尔托获得了168名血红蛋白水平正常，伴有红细胞增多症和低色症的不相关门诊患者的样本。通过间隙PCR，限制性内切核酸酶分析以及HBA2和HBA1基因测序研究了α-地中海贫血突变的存在，而通过测序研究了α-MRE单倍型。我们发现55名（32.7％）患有α地中海贫血突变的个体，51名（30.4％）带有-α3.7缺失，一个带有-α4.2缺失以及三个具有罕见的点突变HBA2：c.-59C> T 。关于alpha-MRE分析，我们观察到单倍型D的频率明显更高，样本中具有-α3.7缺失的非洲人群的特征。这些结果表明，α-地中海贫血突变是乌拉圭无贫血的微细胞增多和低色素血症患者的微细胞减少和低色素血症的重要决定因素，主要原因是-α3.7缺失。α-MRE单倍型和α-地中海贫血突变谱表明，这些突变在乌拉圭占主导地位，但并非唯一的非洲起源。