Factor VIII gene rearrangements in patients with severe haemophilia A.

Abstract

Sequences within intron 22 of the factor VIII (FVIII) gene have been implicated in the cause of haemophilia in almost 50% of severely affected patients. The changes result from intrachromosomal rearrangements of the tip of the long arm of the X chromosome, one break-point being within intron 22 of the FVIII gene. The rearrangements can be identified by Southern blot and we report use of this procedure to detect rearrangements in 11 of 23 unrelated families with severe haemophilia A. Of 22 patients studied, none of the 10 with the gene rearrangement had at any time developed inhibitors to FVIII, compared with 7 of 12 lacking the rearrangement.