Factor VIII Intron 22 Inversion in Severe Hemophilia A Patients in Palestine
أبو عرّه, قيصر محمود
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Hemophilia A is X-linked recessive bleeding disorder affecting 1 in 5000 male births, and caused by mutations in FVIII gene which lead to deficiency or dysfunction of coagulation factor VIII protein. In severe cases, intron 22 inversion (Inv22) of the FVIII gene is a major cause of disease worldwide accounting up to 50% of all FVIII mutations. While intron 1 inversion (Inv1) and small scale mutations of FVIII mutations are responsible for 5% and 45%, respectively. The aim of the present study was to investigate intron 22 inversion mutations among severe hemophilia Apatients as well as carrier status among hemophilia A patients in Palestine. A cohort of 77 hemophilia A individuals (72 males and 5 females) from 52 unrelated families in West Bank area of Palestine was studied. FVIII activity was measured for all male individuals by one stage coagulation assay. Subcycling PCR (S-PCR) was performed fordetectionof Inv22 mutation for all severe male cases as well as mothers. FVIII activity results showed that 41.7% of our patients with severe hemophilia A, 22.2% with moderate hemophilia A and 36.1% with mild hemophilia A. Analysis of Inv22 by S-PCR revealed that37% of the screened patients with severe hemophilia A have this inversion. This finding is similar to that reported among various populationsworldwide. To the best of our knowledge, no previous studies are available in Palestine to investigate intron 22 inversion mutations among severe hemophilia A. The findings of the present study can be used as a step for genetic counseling. Further investigation on Inv1 mutation and full gene sequencing to look for novel mutations for those patients who approved to be negative for Inv22 mutation would be valuable.