Abstract
Thalassemia intermedia lies between asymptomatic beta-thalassemia carrier state to severe thalassemia Major. XmnI polymorphism is one of the modifying factors of intermedia phenotype. This study intendeds to determine the frequency of Xmn-I polymorphism and its association with different beta chain mutations that would contribute towards the phenotype. 100 whole blood samples of thalassemia intermedia patients were tested for the common beta chain mutations found in Pakistan and then tested for Xmn-I polymorphism. The most common mutation identified in these patients was IVSI-5. Xmn-I polymorphism was found in 79% of the patients, 36% being homozygous and 43% being heterozygous. Xmn-I polymorphism was found in 84.7% of the samples with IVSI-5 mutation, 52.1% of Fr 8-9, 45% of Cap+1, 85.7% of Cd30, 91.66% of HbE, and 33.3% of the samples with deI619 mutation. Whereas delta beta, HbS, IVSI-I showed 100% positivity for Xmn-I polymorphism. The age of start of transfusion was 3 -9 years and had high hemoglobin F levels. All the samples with IVSI-I mutation were homozygous (+/+) for Xmn-I polymorphism. Thus a firm linkage between the XmnI polymorphism and IVSI-I mutation is suggested and that IVSI-I mutation always accompany homozygosity of Xmn-I polymorphism and the coinheritance of the two mutations will lead to a milder phenotype.