Genetic analysis of haemophilia A in Bulgaria

A diagnostical strategy consisting of screening for most common mutations in the factor VIII gene and analysis of a panel of eight linked to the factor VIII gene locus polymorphisms was established.Polymorphic analysis for carrier status determination of haemophilia A was successful in 30 families out of 32 (94%). Carrier status was determined in 25 of a total of 28 women at risk (89%). Fourteen prenatal diagnoses in women at high risk of having a haemophilia A – affected child were performed, resulting in 6 healthy boys and 5 girls.The compound approach proves to be a highly informative and cost-effective strategy for prevention of recurrence of haemophilia A in Bulgaria. DNA analysis facilitates carriership determination and subsequent prenatal diagnosis in the majority of Bulgarian families affected by haemophilia A.Haemophilia A is a common inherited disorder of blood clotting, inherited in a recessive X-linked pattern. The incidence of the disease is estimated at app. 1:8000 males.Affected individuals develop a variable phenotype of hemorrhage into joints and muscles, easy bruising, and prolonged bleeding from wounds. The severity and frequency of bleeding in heamophilia A is inversely related to the amount of residual factor.Haemophilia A is caused by deficiency of factor VIII, a cofactor in the activation of factor X at the middle stages of the coagulation cascade. The gene coding for factor VIII is located in the subtelomeric Xq28 region, comprises 26 exons and spans 186 kb genomic DNA [1,2].By the present moment over 400 mutations leading to haemophilia A have been identified [3,4]. De novo mutations in the factor VIII gene constitute a significant proportion of haemophilia A cases (app. 30% of all cases) [5]. Half of such mutations do not derive from a single germ cell but are attributed to a germline or somatic mosaic originating from a mutation during early embryogenesis [6,7].In approximately 40–50% of the severe cases (25% of all cases) the underlying