Thalassemia syndromes prevail in Mediterranean and South East Asia populations. In Greece and Thailand thalassemias have a high prevalence, creating a major public health problem, with severe socioeconomic impact. of the two basic clinical phenotypes of Thalassemias, (major and Intermedia) thalassemia intermedia (Thal.I) is not well-defined and studied.
The main objective of this project is to establish precise criteria for characterization of Thal.I at the molecular level. This will be achieved by analysis of the a and beta gene cluster defects in a large number of thalassemic patients with mild clinical manifestations. Two populations, known for the high prevalence and the extreme heterogeneity (genetic, hematological, and clinical) of a, B, 6B thalassemias, will be studied. For molecular studies advanced DNA techniques will be applied and new techniques will be introduced when necessary. One of these will be the selection of fetal cells in maternal blood, for DNA analysis and antenatal diagnosis. In each population, the main molecular defects related to Thal.I will be evaluated in respect to the hematological, biochemical and biosynthetic expression of the heterozygous, homozygous or double heterozygous State, utilizing sensitive techniques available in the three collaborating units. The establishment of a precise relation of the molecular defect to hematological and other laboratory findings, will facilitate assessment of the clinical severity of thalassemia intermedia; such assessment will enable clinicians to provide the appropriate treatment and prevention. In addition the prospective molecular, hematological and clinical studies of thalassemic patients with mild clinical manifestations, is expected to clarify the pathogenetic mechanism ameliorating the clinical manifestations in patients with Thal.I. The work is expected to complete existing studies on the characterization and distribution of mutations of thalassemia syndromes in various populations, evaluate new techniques for diagnosis and prevention, and expand therapeutic trials with hydroxyurea to ameliorate the clinical symptoms in selected patients with beta-th/Hbe, beta-th/Hbs diseases and other severe B Thal.I patients.
Funding SchemeCSC - Cost-sharing contracts
2333 AL Leiden