Prevalence of Intron 1 Inversion of Cases With Hemophilia A in North Indian Population

Abstract

Hemophilia A is an X-linked bleeding disorder resulting from heterogeneous mutations in the factor VIII (FVIII) gene. The disease is frequently caused by intron 22 inversion mutation in FVIII gene in approximately 50% cases and by intron 1 inversion (Inv1) in 2% to 5% cases with severe hemophilia A. Both inversion mutations occur due to intrachromosomal recombination between inverted repeats found in intronic sequences in upstream regions located telomeric to the FVIII gene and result in a severe phenotype. Frequency of Inv1 mutation varies in different populations. We have analyzed the frequency of the Inv1 in a group of 110 cases with Hemophilia A from North Indian Population and found 4 inversion-positive cases (3.6%). The Inv1 genotyping was further applied to analyze the hemophilia carrier status of the mother and proband's sister. Direct mutation detection strategy is more perfective in diagnosis of cases, carriers, and in prenatal diagnosis of hemophilia A.