MOLECULAR DIAGNOSIS OF HEMOPHILIA-A IN CHINESE PATIENTS BY AN ANALYSIS OF INVERSIONS IN THE FACTOR-VIII GENE

Hemophilia A is an X-linked bleeding disorder caused by deleterious mu tations in the factor VIII gene. An inversion caused by introchromosom al homologous recombination between the A gene located in intron 22 of the factor VIII gene and one of the two telomeric A genes has been re cently described as the common cause of about 50% of cases of severe h emophilia A. The rearrangement can be readily detected by a Southern b lotting procedure. We report use of this procedure To detect rearrange ments in 106 unrelated Chinese hemophilia A cases. In 49.3% of the pat ients with severe disease an inversion was found but no inversion was detected in arty of the patients with moderate or mild disease. The ma jority of inversions (91.4%) involved the most distal A gene; in a min ority (8.6%) the more proximal A gene was involved, These results indi cate that intron 22 inversion is the most important molecular defect c ausing Chinese hemophilia A and that analysis for intron 22 inversion may be the first-line test in the molecular diagnosis of severe hemoph ilia A.