Abstract: Objective Hemophilia A, an X-linked bleeding disorder, affecting 1 in 5000 males is caused by heterogeneous mutations in factor Ⅷ gene.Inversion mutation in Intron 22 of F8Cgene remains its leading cause.The aim of this study was to evaluate the frequency and distribution of the Intron 22-inversion mutation in the patients and in the family members in the region.Methods 29 hemophilia Apatients from Jammu and Kashmir(20 severe, 8 moderate and 1 mild) were analyzed for Intron 22-inversion mutation.Results 11(38%) were positive for the distal type of inversion mutation.The mutation was found in 9/20(45%) patients with severe factor Ⅷ deficiency and 2/8(25%) with moderate severity hemophilia A, whereas the patient with mild hemophilia Awas found to be negative for inversion mutation.Evaluation of twenty-six female relatives from 11 families of inversion mutation positive patients identified one mother and one sister from one family to be the carrier, suggesting its origin in the mother.Conclusion The present study confirms the intron-22 inversion mutation in F8Cgene as the major cause of hemophilia Ain the population from Jammu and Kashmir with a higher frequency of inversion mutation in sporadic cases compared to the familial cases.

Key words: hemophilia A, factor Ⅷ, inversion, Intron 22