Analysis of Intron 22 Inversions of the Factor VI11 Gene in Severe Hemophilia A: Implications for Genetic Counseling

lntrachromosomal recombinations involving F8A. in intron 22 of the factor Vlll gene, and one of two homologous re-gions 500 kb 5 ’ of the factor Vlll gene result in large inver-sions of DNA at the tip of the X chromosome. The gene is disrupted, causing severe hemophilia A. Two inversions are possible, distal and proximal, depending on which homolo-gous region is involved in the recombination event. A simple Southern blotting technique was used to identify patients and carriers of these inversions. In a group of 85 severe hemophilia A patients, 47 % had an inversion, of which 80% were of the distal type. There was no association with re-striction fragment length polymorphism (RFLP) haplotypes. The technique has identified a definitive genetic marker in EVERE HEMOPHILIA A is caused by a deficiency of coagulation factor VI11 (FVIII) of less than 2 interna