Mutation in thalassemia syndrome and clinical manifestation

Abstract

Introduction: Thalassemia intermedia is a term used to define a group of patients with β thalassemia in whom the clinical severity of the disease is somewhere between the mild symptoms of the β thalassemia trait and the severe manifestations of β thalassemia major. Thalassemia intermedia shows considerable heterogeneity in phenotype and molecular basis. Objectives: The aim of this study was to identify the common mutations of beta globin gene and the relationship between genotypes and phenotypes in thalassemia intermedia patients in Mazandaran province, in the north of Iran. Patients and Methods: Fifty unrelated thalassemia intermedia patients, based on clinical and hematological characteristics including age of diagnosis, age of first blood transfusion, history of blood transfusion, mean corpuscular volume (MCV), mean cell hemoglobin (MCH), hemoglobin values, and liver and spleen status were selected. DNA of peripheral blood was extracted and common mutations in beta globin gene were analyzed by reverse dot blot (RDB) method. Results: Our study showed that 30 patients (60%) had blood transfusion. There was no obvious hepatomegaly in any of the subjects, however 40 patients (80%) showed splenomegaly among which 34 cases (68%) underwent splenectomy. Mutations analysis indicated that HBB:c.315+1G>A [IVS II-1 (G>A)] mutation was the dominant mutation and has been widely associated with the phenotypic manifestations of thalassemia intermedia patients. Conclusion: It is important to comprehend the molecular basis of thalassemia intermedia and the association between genotype and phenotype in different ethnic groups. Therefore a careful evaluation of genetic, molecular, hematological and clinical aspects is necessary to differentiate thalassemia intermedia in patients at presentation.