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 mutations in the factor VIII gene. An inversion caused by introchromosomal 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 recently described as the common cause of about 50% of cases of severe hemophilia A. The rearrangement can be readily detected by a Southern blotting procedure. We report use of this procedure To detect rearrangements in 106 unrelated Chinese hemophilia A cases. In 49.3% of the patients with severe disease an inversion was found but no inversion was detected in arty of the patients with moderate or mild disease. The majority of inversions (91.4%) involved the most distal A gene; in a minority (8.6%) the more proximal A gene was involved, These results indicate that intron 22 inversion is the most important molecular defect causing Chinese hemophilia A and that analysis for intron 22 inversion may be the first-line test in the molecular diagnosis of severe hemophilia A.