Molecular Basis of beta-Thalassemia in Indonesia: Application to Prenatal Diagnosis

Background: To facilitate an effective prevention program, the beta-thalassemia mutations in the different ethnic groups in Indonesia were characterized. Methods and Results: The amplification refractory mutation system and artificially created restriction site were used to detect seven known mutations previously described in the Indonesian population. Other mutant alleles were identified by chemical cleavage mismatch, double-stranded sequencing, and Southern blotting. With these methods 78% of beta-thalassemia mutant alleles have been detected so far. Thirteen different beta-thalassemia mutations were characterized, nine of which had previously been described in the Jakarta population. The most frequent mutation is HbE (29%), followed by IVS1-nt5 (19%), and Cd 35 (8%). The frequencies of the other mutations varied from 4% to less than 1%. Two large gene deletions, Filipino beta-deletion and Hb Lepore, were identified in patients from the eastern part of Indonesia. Conclusions: The ethnicity and clinical hematology of cases in the region should be considered in the screening strategy for carriers and antenatal diagnosis of beta-thalassemia in Indonesia. Direct sequencing proved to be the appropriate method for detecting the unknown mutations, and Southern blotting had to be used for large deletions.