Screening for hemophilia A carriers: utility of PCR-RFLP--based polymorphism analysis

Health schemes are promoting application of molecular diagnosis and screening in peripheral diagnostics labs. Intragenic restriction fragment length polymorphisms in the intron 18 (BclI), intron 19 (HindIII), and intron 22 (XbaI) of the Factor VIII gene were studied in 100 patients with hemophilia A and their relatives at risk from different regions of north India. For Bcl I, HindIII, and XbaI, the positive allele frequency was 0.57, 0.38, and 0.43, respectively, and heterozygosity was 0.54, 0.49, 0.41, respectively, whereas the heterozygosity in terms of informativity of the above markers was 53% for BclI, 44% for HindIII, and 34% for XbaI. Combined informativity of these markers was 77%. Review of Indian and world literature shows a marked variation in the informativity of polymorphic sites. Screening for carriers forms the baseline for prevention of hemophilia A. Polymerase chain reaction-restriction fragment length polymorphism is a low-cost procedure, efficient in the north Indian population.