What is the genetic basis of Hemophilia A?

Hemophilia A is a genetic disorder characterized by a deficiency in clotting factor VIII, which is essential for proper blood coagulation. The underlying genetic basis of Hemophilia A is primarily due to mutations in the F8 gene located on the X chromosome. Since males have one X and one Y chromosome, a mutation in their single X chromosome will result in the manifestation of the disease. Females have two X chromosomes, so a mutation must be present in both for the disease to manifest, which is why females are often carriers and may present with milder symptoms.

The classification of Hemophilia A as an X-linked recessive disorder explains its epidemiology. It is more common in males than females due to the way X-linked inheritance operates. If a male inherits the mutated X chromosome, he will express the condition. In contrast, a female would require two mutated copies of the gene to develop Hemophilia A, which is much less likely, thus leading to a higher prevalence in males.

This mode of inheritance is crucial for understanding the genetic counseling and risk assessment for families affected by Hemophilia A, as the pattern of inheritance can influence the likelihood of passing the disorder to offspring and informs management and treatment options.