RESUMO
BACKGROUND: Thalassemia is one of the most prevalent worldwide autosomal recessive disorders characterized by a great molecular and clinical expression heterogeneity. Alpha and beta-thalassemia are the main two types observed in case of mutations affecting alpha and beta-globin genes respectively. Delta-thalassemia is noted when mutations occur on the delta-globin gene. In Tunisia, ß-thalassemia prevalence is estimated at 2.21% of carriers. However, few reports investigated the delta-globin gene. OBJECTIVES: In this work, we aimed to perform a molecular study to help define the molecular spectrum of δ-thalassemia mutations in Tunisia. PATIENTS AND METHODS: The study involved 7558 patients among whom we selected 179 individuals with abnormal HbA2 values or fractions. Hemoglobin analysis was performed using Capillary electrophoresis (CE) and high-performance liquid chromatography (HPLC). DNA sequencing was performed on ABI prism 310 Genetic Analyzer Applied Biosystems. CUPSAT (Cologne University Protein Stability Analysis Tool) was used for the prediction of protein stability changes upon missense mutations and mutants were modeled via DeepView-SwissPdbViewer and POV-Ray softwares for molecular dynamics simulation studies. RESULTS: We identified four mutations: HbA2-Yialousa described for the first time in Tunisia ( in 72.72% of cases) and 3 mutations reported for the first time in the world: (i) c.442 T > C Stop147Arg ext 15aa-stop observed in 18.18% of cases, (ii) c.187 G > C (Ala62Pro) noted in 4.54% of cases and (iii) c.93-1G > C found in 4.54% of cases. CONCLUSION: Our data provide genetic basis that would be especially useful in screening for beta-thalassemia trait during delta-beta thalassemia associations.
