Hemophilia A Patients with Undetectable Mutations: Current Knowledge and Future Directions*

Absence or decreased activity of the F8 protein causes hemophilia A (HA) which is characterized by the occurrence of spontaneous bleeding. Mutations in the F8 gene, located at the telomeric end of the long arm of the X chromosome, have been identified as the cause of HA. Such mutations include the intron 22 and intron 1 inversions hot spots, point mutations (nonsense and missense mutations) that are distributed throughout all exons and various deletions and insertions [1]. For a review on mutation analysis and therapy refer to Graw et al. [2]. Recently, Oldenburg et al. [3] published the distribution of different types of mutations in the F8 gene (table 1). Patients with detectable mutations in the F8 gene account for a total of 98.2% of all patients. In the remaining 1.8% of paHemophilia A Patients with Undetectable Mutations: Current Knowledge and Future Directions*