Molecular basis of alpha-thalassemia in Iran

Alpha-thalassemia [alpha-thal] is probably the most prevalent monogenic condition in the world. Deletions are the most common types of mutations in alpha-thal, followed by point mutations and small insertion/deletion. In the context of national screening program for prevention of thalassemia and hemoglobinopathies in Iran, alpha-thal carriers have come to more attention. Therefore, the frequency and distribution of alpha-globin mutations in various regions of the country have been studied in recent years. A comprehensive search was performed in PubMed, Scopus, and national databases for finding reports on mutation detection in alpha-thal carriers and HbH disease with Iranian origin. The mutation data of 10849 alpha-thal carriers showed that -alpha[3.7] and alpha[-5NT] were the most common deletional and nondeletional mutations, respectively. In HbH disease cases, the -alpha[3.7]/-[-MED] was the most prevalent genotype. Overall, 42 different mutations have been identified in alpha-globin cluster reflecting the high heterogeneity of the mutations in Iranian populations

First report on the Co-inheritance of beta-globin IVS-I-5 [G-C] thalassemia with delta globin CD12 [Asn-Lys [AAT-AAA]] hba2- NYU in Iran

Background: co-inheritance of beta- and delta-globin mutations in Iran is not uncommon. This situation may interfere with correct diagnosis and genetic counseling of alpha- and beta-thalassemia in screening programs. Here we report the co-inheritance of beta- and delta-globin gene mutations in an individual with microcytosis, hypochromia and a normal hemoglobin A2 [HbA2] level

Methods: genomic DNA extraction, amplication refractory mutation system [ARMS] polymerase chain reaction and direct DNA sequencing of delta- and beta-globin genes were exploited for detection of the mutations in these two genes in an individual with low hematological indices and normal HbA2

Results: ARMS-PCR technique revealed the beta+ IVSI-5 [G to C] mutation and direct DNA sequencing of the delta-globin gene detected a previously reported delta codon 12 [AATàAAA] HbA2-NYU. This study reports HbA2-NYU in association with the beta IVSI-5 [G to C] mutation in Iran

Discussion: this report emphasizes that normal HbA2 expression in a beta-goblin carrier is due to mutation in the delta-globin gene and may cause misdiagnosis of thalassemia

Co-inheritance of hemoglobin D and beta-thalassemia traits in three Iranian families: clinical relevance

Here we report the result of three cases referred to our lab that had a combination of beta-thalassemia and hemoglobin D [Hb D] traits. These individuals had no symptoms of profound anemia and hematological indices were similar to that of a beta-thalassemia heterozygote. In all three cases, the Hb D level was elevated and no HbA was detected electrophoretically. The electrophoresis pattern suggested that all cases were homozygotes for Hb D. PCR followed by digestion with EcoRI and sequencing of the beta-globin gene confirmed the presence of Cd 121 GAA>CAA in the heterozygous form with another beta-globin mutation. In all cases, the mutations in the beta-globin gene were detected by ARMS PCR technique and they were either IVSII-I or IVSI-5. Hematological studies of the family members showed that thalassemia which caused the mutations and Hb D were in the Trans position