Beta thalassemia intermedia, as one of the significant types of thalassemia syndromes, is seen among approximately 10% of patients with beta thalassemia. Recent advances in molecular genetics have disclosed that the conjunction defects of beta thalassemia with a triplicated alpha globin gene loci may constitute a major cause of beta thalassemia intermedia phenotype. Our proposal seeks to exploit the molecular technics of the rapid detection of the most common alpha alpha alpha (anti3.7) haplotype, combined with the technique of micro DNA sampling (MDS) from dried blood for detection of beta thalassemia mutations, to develop a simple and reliable diagnostic kit that will provide a new resource for the diagnosis of beta thalassemia intermedia in clinical labs and large population studies.The new kit will also play an important role in more accurate understandings of the frequencies of the triplicated alpha loci haplotypes (as well as the mutant beta thalassemia alleles) and eventually further improvement of the management and prevention programs for beta thalassemia intermedia. Beta thalassemia is one of the most common blood disorders, with a high frequency and a wide distribution in Africa, Asia, and in the Mediterranean region. In the past decade, about 90% of genetic lesions in beta thalassemia were well defined. Consequently, a number of molecular techniques as well as diagnostic kits have been developed and used in those patients who carried known mutant alleles. Unfortunately, molecular diagnosis could not be completed by the available kits in the remainder 10% of patients who are mostly manifesting a phenotype of beta thalassemia intermedia.Our proposal seeks to exploit the recent advances in the molecular analysis of beta thalassemia intermedia, combined with our simple MDS method to develop a new molecular diagnostic kit for beta thalassemia intermedia that can be easily utilized in clinics and in the regions where the disease is prevalent.National Heart, Lung, and Blood Institute (NHLBI)
