Molecular genetics and counselling in haemophilia

Genetic analysis of the human factor VIII and IX genes has resulted in accurate carrier detection and prenatal diagnosis based on either informative DNA polymorphisms or on causative mutations. By combined use of up to 10 polymorphisms within the factor IX gene, over 90% of families are informative. Within the factor VIII gene the multiallelic CA repeats in introns 13 and 22 can be analysed by multiplex PCR resulting also in over 80% of families being informative. Mutation detection has developed with advancing technology which can be used to identify mutations in the factor IX gene in practically all patients with haemophilia B and their relatives. Although this is more technically demanding for patients with haemophilia A because of the greater complexity of the factor VIII gene, the recent description of X-chromosome inversions as a cause of severe haemophilia A in almost 50% of patients has led to the ready detection of these inversions in such families with associated precise carrier detection.