Prevalence of Intron 22 Inversions in Pakistani Hemophilic Patients

Background and Objectives: Hemophilia A is characterized by deficiency in factor VIII clotting activity that results in prolonged bleeding after injuries, tooth extractions, or surgery, and delayed or recurrent bleeding prior to complete wound healing. The age of diagnosis and frequency of bleeding episodes are related to the level of factor VIII clotting activity. It is caused by the mutations in factor VIII (F8) gene. In severe HA, intron 22 inversions (IVS-22) of the F8 gene is the most prevalent mutation accounting up to 50 % of all mutations. The knowledge of the pathogenetic mutation is important for i) the basis of carrier detection and ii) for the risk estimation of inhibitor formation. Material and Methods: We studied 50 unrelated patients suffering from severe HA reporting to Fatimid Hemophilia Center, Karachi. Proforma for each patient was filled. Subcycling Polymerase Chain Reaction (SPCR) was performed to detect IVS-22. Results: The bands were observed s at 12 kb on the upper level and 10 kb band at lower level in which IVS-22 was absent. Whereas bands at 11 kb and 10 kb position signifies IVS-22. The number of patients with IVS-22 accounted to 44%. Conclusion: IVS-22 is the major genetic mutation for severe hemophilia A. The results were consistent with the concept that IVS-22 will always result in severe deficiency of F8. Rapid detection of this common mutation can helpfully guide the direction of molecular study in genetic counseling.