Factor VIII Intron 22 Inversion Mutation in Samples of Iraqi Patients with Hemophilia A

Abstract

Background:Hemophilia A is an X-linked recessive inherited bleeding illness characterized by a lack of procoagulant factor VIII; the factor VIII gene has more than 3000 different mutations, and the most frequent molecular changes in severe hemophilia A are intron 22 and intron 1 inversions (Inv 22 and Inv 1). Objectives:To detect intron 22 inversion mutation in samples of Iraqi patients with hemophilia A and reveal its role in inhibitor production. Materials and Methods:Eighty patients with hemophilia A were enrolled in this study from two Iraqi centers. The specialist centers for hemophilia in Babil Teaching Hospital for Maternity and Children and Welfare Teaching Hospital. Genetic analysis of the Inv 22 mutation was done by real-time thermal cyclic quantitative PCR (qPCR). Mixing study and Bethesda assay were used for the detection of inhibitor development. Results:Eighty patients with hemophilia A were partitioned into 22 (27.5%) with inhibitors and 58 (72.5%) without inhibitors. Most patients (48.8%) were diagnosed at age 6–9 months; according to the disease severity, patients were divided into severe hemophilia 76.25%, moderate hemophilia 16.25%, and mild hemophilia 7.5%. Among all patients, positive Inv22 mutation was detected in 83.7%. Conclusion:the results of inversion 22 are consistent with overall reports, being a significant major genetic transformation in severe hemophilia A. q-PCR is a basic, fast method for the detection of inversion 22. The mutation is detected in 74.6% of severe cases and is considered an important risk factor for inhibitor production.

Keywords

• factor viii
• hemophilia a
• inversion 22