Author(s): Lakich D, Kazazian HH Jr, Antonarakis SE, Gitschier J
Abstract Share this page
Abstract Mutations in the factor VIII gene have been discovered for barely more than half of the examined cases of severe haemophilia A. To account for the unidentified mutations, we propose a model based on the possibility of recombination between homologous sequences located in intron 22 and upstream of the factor VIII gene. Such a recombination would lead to an inversion of all intervening DNA and a disruption of the gene. We present evidence to support this model and describe a Southern blot assay that detects the inversion. These findings should be valuable for genetic prediction of haemophilia A in approximately 45\% of families with severe disease.
This article was published in Nat Genet
and referenced in Journal of Genetic Syndromes & Gene Therapy