SCREENING FOR INVERSIONS IN THE FACTOR-VIII (F8) GENE CAUSING SEVERE HEMOPHILIA-A

A total of 164 unrelated patients with severe haemophilia A were scree ned for partial inversions of the factor VIII (F8) gene resulting from recombination between the intronic F8A gene and one or other of two h omologous upstream A gene sequences. Inversions were found in 69 (42%) patients. Most inversions (90%) involved the distal rather than the p roximal A gene. This unique mutational mechanism is estimated to occur with a frequency of 7.2 x 10(-6) per gene per gamete per generation. Although two patients with an inversion possessed inhibitors (antibodi es) against factor VIII, possession of inhibitors did not appear to be associated disproportionately with inversion-type mutations.