MOLECULAR CHARACTERIZATION OF BETA-THALASSEMIA IN PAKISTAN

beta-Thalassemia is one of the most common inherited hemoglobin disord ers in Pakistan. The carrier frequency is estimated to be 5.4%. To det ermine the spectrum of beta-globin gene defects causing beta-thalassem ia, we have analyzed a representative sample of 602 alleles from six e thnic groups in Pakistan; 99.2% alleles were characterized, while 0.8% remained unidentified. The spectrum of. mutations is heterogeneous an d we have found 19 different mutations in all ethnic groups. The four most common mutations, IVS-I-5 (G-->C) (37.7%), codons 8/9 (+G) (21.1% ), the 619 bp deletion (12.4%), and IVS-I-1 (G-->T) (9.5%), account fo r 80.7% of the alleles. There are differences between the ethnic group s and also between provinces. In the four provinces of Pakistan, the I VS-I-5 (G-->C) mutation is more prevalent in Sindh and Balochistan, bo rdering India in the south and Iran in the southwest, while the codons 8/9 (+G) mutation is more common in the Punjab and the North West Fro ntier Province, bordering India in the northeast and Afghanistan, resp ectively. The 619 bp deletion is high (46%) in Gujratis and Memons res iding in the Province of Sindh, neighboring the Indian Gujrat.