Hemophilia A is a rare hereditary hemorrhage disorder characterized by X-linked recessive inheritance that develops as deficiency of Factor VIII and is manifested by intraarticular (hemarthrosis) and intramuscular (hematoma) hemorrhages. Hemophilia A occurs one in approximately 5,000-10,000 male births. The severity of the disease is higher among the youngest patients and the clinical symptoms are experienced more severely. The disease is mostly transmitted to male children from carrier women. About one-third of cases may occur with spontaneous de-novo mutations without a family history.
The severity of hemorrhage findings is directly related to the degree of deficiency of factor VIII. Patients with factor activity (1% exhibit “severe hemophilia” clinical symptoms, while those with 1-5% exhibit “moderate hemophilia” clinical symptoms, and those with) 5% exhibit “mild hemophilia” clinical symptoms.
The molecular changes in the F8 gene, which are responsible for hemophilia A, can be divided into 3 groups:
1. Large gene rearrangements
2. Intragenic deletions or insertions
3. Single nucleotide changes
Around 5,000 variants have been reported in the Hemophilia A mutation databases. Because of the molecular pathologies in all these classes, the disease may take a severe form. However, the inversion including the F8 intron 22 has been found to be responsible for about 40-50% of severe hemophilia A cases. The most common mutation mechanism, independent of the degree of severity, may be determined as single base changes for hemophilia A.