MOLECULAR DEFECTS IN BETA-THALASSEMIAS IN THE POPULATION OF SAUDI-ARABIA

The beta-thalassaemias are a heterogeneous group of inherited disorder s caused by mutations in and around the structural gene of the beta-ch ain of the adult haemoglobin (HbA). Studies at the gene level have ide ntified a large number of beta-thalassaemia gene variations in differe nt populations. These findings have implications for the use of molecu lar diagnosis for genetic counselling and prenatal detection of the be ta-thalassaemias. In our unit, we initiated studies to investigate the molecular defects in beta-thalassaemias in Saudi Arabia using amplifi cation-refractory mutation systems, dot blot analysis and restriction endonuclease analysis, and identified mutations producing beta(+)- and beta(o)-thalassaemias. Twenty of the mutations encountered in the Asi an, Mediterranean, Chinese and other Arab populations were investigate d. The most commonly encountered mutations in Saudi beta-thalassaemia patients were IVS-I-110, IVS-II-1, CD 39, IVS-I-5 and IVS-I 3' end (-2 5), while frameshifts at CD 8/9, Cap+1 (A --> C) and CD 6 mutations we re identified at a low frequency. These mutations account for 84.94% o f the total beta-thalassaemia mutations. The remaining 15% remain unkn own. This is the first report on the type and nature of mutations in S audi beta-thalassaemia patients. It presents frequencies of twenty mut ations and emphasises the need for further detailed investigations to clarify the whole spectrum of beta-thalassaemia mutations in the Saudi population.