Background: Hemophilia A is an X-linked recessively inherited bleeding disorder characterized by deficiency of procoagulant factor VIII (FVIII).
Methods: Sixty unrelated hemophilia A patients and their family members have undergone tests for carrier detection by linkage analysis using the polymorphic markers Bcl I, Xba I and Intron 13 or 22 VNTRs. In families of sporadic hemophiliacs, the carrier status of female subjects was ascertained by linkage analysis along with FVIII:C/VWD Ag estimation.
Results: Of the 33 families with positive family history, the defective X chromosome was tracked in 28 mothers. The carrier status of females from hemophilia A families with positive family history, ascertained by linkage analysis and Intron 22 and 1 inversion, was made out in 85% cases. FVIII:C/VWF Ag ratio was evaluated in 36 females from 9 sporadic hemophilic families. Using the FVIII:C/VWF Ag ratio along with linkage analysis, carrier status was determined in 9 (25%) of the 36 females studied. Using Intron 22 inversion along with linkage analysis and FVIII:C/VWF Ag estimation, the informativity in female subjects from families of sporadic hemophiliacs increased from 25% to 52%.
Conclusion: In the West, linkage analysis with Bcl I, Xba I and Intron 13 or 22 VNTR markers and inversion 22 offers a good tool for carrier detection of hemophilia A in India.