Farashi Samaneh, Faramarzi Garous Negin, Zeinali Fatemeh, Vakili Shadi, Ashki Mehri, Imanian Hashem, Najmabadi Hossein, Azarkeivan Azita, Tamaddoni Ahmad
Kariminejad-Najmabadi Pathology & Genetics Center , Tehran , Iran .
Hemoglobin. 2015;39(3):196-200. doi: 10.3109/03630269.2015.1030757. Epub 2015 May 15.
α-Thalassemia (α-thal) is a common genetic disorder in Iran and many parts of the world. Genetic defects in the α-globin gene cluster can result in α-thal that may develop into a clinical phenotype varying from almost asymptomatic to a lethal hemolytic anemia. Loss of one functional α gene, indicated as heterozygous α(+)-thal, shows minor hematological abnormalities. Homozygosity for α(+)- or heterozygosity for α(0)-thal have more severe hematological abnormalities due to a markedly reduced α chain output. At the molecular level, the absence of three α-globin genes resulting from the compound heterozygous state for α(0)- and α(+)-thal, lead to Hb H disease. Here we present a 21 nucleotide (nt) duplication consisting of six amino acids and 3 bp of intronic sequence at the exon-intron boundary, in both the α-globin genes, detected by direct DNA sequencing. This duplication was identified in three patients originating from two different Iranian ethnic groups and one Arab during more than 12 years. The clinical presentation of these individuals varies widely from a mild asymptomatic anemia (heterozygote in α1-globin gene) to a severely anemic state, diagnosed as an Hb H individual requiring blood transfusion (duplication on the α2-globin gene in combination with the - -(MED) double α-globin gene deletion). The third individual, who was homozygous for this nt duplication on the α1-globin gene, showed severe hypochromic microcytic anemia and splenomegaly. In the last decade, numerous α-globin mutations have demonstrated the necessity of prenatal diagnosis (PND) for α-thal, and this study has contributed another mutation as important enough that needs to be considered.
α地中海贫血（α-thal）是伊朗和世界许多地区常见的遗传性疾病。α珠蛋白基因簇的遗传缺陷可导致α地中海贫血，其临床表型可从几乎无症状到致命的溶血性贫血不等。一个功能性α基因缺失，即杂合性α（+）-地中海贫血，表现出轻微的血液学异常。α（+）-地中海贫血的纯合子或α（0）-地中海贫血的杂合子由于α链产量明显降低，血液学异常更为严重。在分子水平上，α（0）-和α（+）-地中海贫血的复合杂合状态导致三个α珠蛋白基因缺失，从而引发血红蛋白H病。在此，我们通过直接DNA测序在两个α珠蛋白基因中检测到一个21个核苷酸（nt）的重复序列，该序列由六个氨基酸和外显子-内含子边界处3bp的内含子序列组成。在超过12年的时间里，在来自两个不同伊朗族群和一个阿拉伯族群的三名患者中发现了这种重复序列。这些个体的临床表现差异很大，从轻度无症状贫血（α1珠蛋白基因杂合子）到严重贫血状态，后者被诊断为需要输血的血红蛋白H个体（α2珠蛋白基因上的重复序列与 - -（MED）双α珠蛋白基因缺失相结合）。第三名个体在α1珠蛋白基因上对该nt重复序列呈纯合状态，表现出严重的低色素小细胞贫血和脾肿大。在过去十年中，众多α珠蛋白突变已证明对α地中海贫血进行产前诊断（PND）的必要性，本研究又发现了另一个足够重要的突变，需要加以考虑。
