Evaluation of delta globin gene variations reducing hemoglobin A2

Introduction and purpose: Beta thalassemia is a hemoglobinopathy which results from hemoglobin beta globin synthesis defect. HbA2 levels ​​assessed by high performance liquid chromatography (HPLC) are essential parameter for the diagnosis of beta thalassemia carriers. HbA2 level is expected to be increased in beta thalassemia carriers. However, in some cases, the HbA 2 level does not increase. Among the causes that lowered HbA2 level, the least researched is the delta globin gene variations. Although delta globin gene variations have no clinical implications, the co-inheritance of beta thalassemia mutations may lead to misdiagnosis. Because, HbA2 levels remain normal or low due to decreased delta chain production. For this reason, the detection of delta globin variations is important in countries that have a high incidence of beta thalassemia carriers. In this study, we aimed to reveal the HBD gene variations by sequence analysis to investigate the frequency and types of these variations in our country where beta thalassemia is common. Materials & Methods: A total of 50 patients who applied for the analysis of alpha or beta thalassemia mutations in Ege University Medical Faculty Hospital Medical Genetics Department were included in the study. There were 40 cases presenting microcytosis and hypochromia with the HbA2 level of 2% or less than 2% and 10 cases with a second peak in the HbA 2 fraction. In these cases, HBD gene changes were investigated by Sanger sequence analysis. Results: In this study, seven different variations were detected in 8 cases. Five of the 7 detected variations have been described previously. Two variations were identified for the first time in this study. Seven variations defined in the study were as fallows; 1 previously reported c.115 A>G mutation in one case; 1 previously reported c.14 C>T mutation and 2 benign variations (c.294 C>T, c.316-174_316- 173delAT) in one case; 1 novel c.350 G>C variation, which formed a variant hemoglobin and was first described in this study; 2 variations (c.315+429 T>C, c.-172 A>T), one of was defined in this study in 5 cases were identified. Conclusion: One of the two novel variants was introduced to world literature as a new hemoglobin variant HbA 2 -Bornova and the other was benign according to ACMG criteria. This study contributed to the phenotype-genotype correlation by evaluating the laboratory findings of the cases that detected variation. HBD gene sequencing analysis was assessed for the first time,in our knowledge, in the Turkish population.