Carrier detection and prenatal diagnosis of haemophilia. Present and future strategies.

Abstract

The advent of molecular genetics has had a significant impact on carrier detection and prenatal diagnosis in the haemophilias. Where phenotypic analysis can only identify with varying degrees of probability up to 90% of carriers and can only be used in prenatal diagnosis when fetal blood is obtained (18-20 weeks gestation), genotypic analysis gives a greater than 99% certainty of carrier status (when informative) and allows for prenatal diagnosis at 8-12 weeks utilising DNA obtained by chorionic villus sampling. Furthermore, the introduction of the technique of polymerase chain reaction (PCR) amplification of DNA into genotypic analysis either for the detection of the disease-causing defect itself, or to detect an intragenic informative polymorphism, has significantly increased the ease by which these procedures can be introduced into the laboratory. PCR based family studies in haemophilia will become increasingly available in both developed and developing countries. While in the former detection of the defect itself will become available, particularly for haemophilia B, in other countries simple PCR based DNA polymorphism analysis will become the mainstay of effective, practical haemophilia genetics.