Genetic basis - Caused by a mutation in the F8 gene, which encodes coagulation Factor VIII, crucial for blood clotting. The mutation identified in Boxer dogs is a single nucleotide substitution (c.1412C>G) in exon 10, resulting in an amino acid change (P471R) in the A2 domain of Factor VIII. The disorder follows an X-linked recessive inheritance pattern as the F8 gene is located on the X chromosome. Males with one mutated X chromosome are affected; females with one mutated copy are carriers and are typically asymptomatic.
Pathophysiology - The mutation leads to reduced or absent Factor VIII activity, impairing the intrinsic coagulation pathway. This results in an inability to form stable blood clots, causing bleeding episodes.
Complications - Clinical signs include spontaneous or prolonged bleeding, hematomas, bleeding into joints (hemarthrosis), bruising, and bleeding after surgery or trauma. Excessive bleeding can be life-threatening without appropriate treatment.
Why This Matters to Breeders and Vets - Prevents producing puppies with severe bleeding disorders, improving breed health and welfare. Facilitates early diagnosis and management of bleeding episodes by veterinarians. Supports informed breeding decisions based on X-linked inheritance patterns. Contributes to long-term reduction of hemophilia A in Boxers.