PRENATAL DIAGNOSIS FOR THALASSAEMIA IN A MULTICULTURAL SOCIETY

Authors: R. J. TRENT1,2*, H. LE1 AND B. YU1,2
1Department of Molecular and Clinical Genetics, Royal Prince Alfred Hospital, Missenden Road, Camperdown,
NSW 2050, Australia 2Department of Medicine, University of Sydney, NSW 2006, Australia

SUMMARY

The provision of a prenatal diagnosis service for thalassaemia is becoming more demanding. In an ethnicallydiverse
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 á/â 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 â thalassaemia mutations. The actual prenatal test is undertaken using two independent PCRs thereby
reducing the potential for error. Despite the advantages of PCR, 212 per cent of â thalassaemia and about nine per
cent of á 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