Alpha‐globin gene mutation spectrum in patients with microcytic hypochromic anemia from Mazandaran Province, Iran

BACKGROUND: It is estimated about 7% of the world population is carriers of hemoglobin diseases. Alpha‐thalassemia is one of the most common hereditary hemoglobin disorders in the world. This study investigated alpha‐globin mutations in potential carriers with hypochromic and microcytic anemia from Mazandaran, in northern Iran. METHODS: A total of 859 subjects were selected; genomic DNA was extracted and examined for the presence of mutations in the alpha‐globin genes. RESULTS: Mutation analysis of alpha‐globin genes revealed 27 different mutations. Seven variants were seen in 91.45% of all alpha‐1 and alpha‐2 mutations among patients in this study. The 3.7 kb deletion is the most frequent mutation with a frequency of 49.53%, followed by PolyA2 (15.19%), −4.2 deletion (8.76%), ‐‐MED (5.84%), IVSI‐5nt deletion (5.49%), Hb constant spring (3.62%), and Cd 19 (−G; 3.04%), respectively. There are also seven new variants which were reported for the first time either in alpha‐1 or alpha‐2 genes, including codon 9 (C > A; α2), deletion of codon 60 (AAG deletion; α2), duplication of codon 94‐100 plus 3 base pairs of intron 2 (IVSII + 3; α1), codon 99 (C > A; α2), codon 108 (A > G; α2), codon 128 (A > T; α2), and codon 129 (T > G; α2), respectively. The MLPA method also revealed three rare and novel deletions in alpha‐cluster region with about 30 kilobases long. CONCLUSION: This study showed an efficient identification of α‐thalassemia can be achieved using standard hematological indices in our population. The details of these variations will help local genetic services for diagnostic and prenatal diagnosis services.