Prenatal diagnosis for thalassaemia in a multicultural society

The provision of a prenatal diagnosis service for thalassaemia is becoming more demanding. In an ethnically-diverse community, the number of mutations has increased. Requests for prenatal testing continue to come at an advanced stage in pregnancy, often without the underlying mutation having been identified. Although controls are included in PCR assays, errors can still occur. The alternative to DNA testing, i.e., an α/β globin chain synthesis ratio on a fetal blood sample, is now less readily available. In the circumstances described, the laboratory must adopt a more efficient and reliable approach to DNA mutation analysis. With currently available technology, this improvement is more likely to come through increased automation. To achieve this aim, we have moved to capillary electrophoresis. With capillary electrophoresis we are able to use a PCR-based screening strategy which can detect up to 11 β thalassaemia mutations. The actual prenatal test is undertaken using two independent PCRs thereby reducing the potential for error. Despite the advantages of PCR, ∼12 per cent of β thalassaemia and about nine per cent of α thalassaemia cases require further study in our experience. In this situation, capillary electrophoresis has again proven helpful since a DNA scanning approach, such as single strand conformation polymorphism, can be automated to identify the region of DNA to be sequenced.