Prenatal DNA diagnosis of Down's syndrome by PCR

Abstract

L Verma and colleagues (July 4, p 9)1Verma L Macdonald F Leedham P McConachie M Dhanjal S Hultén M Rapid and simple prenatal DNA diagnosis of Down's syndrome.Lancet. 1998; 352: 9-12Summary Full Text Full Text PDF PubMed Scopus (114) Google Scholar describe a novel approach to prenatal diagnosis of Down's syndrome. Unfortunately, since this work was supported by the National Health Service (NHS) Executive Research & Development Programme Health Technology Assessment, readers might conclude that this is now the approved, quick, low-cost alternative that will rapidly replace routine karotyping. Conventional cytogenetic studies are not cheap and do not provide instant results. They are, however, accurate and effective. The high standards in the UK and other countries have been developed over many years in conjunction with obstetricians and in response to patient demand. Although aneuploidy screening, with either PCR or fluorescence in-situ hybridisation (FISH)-based protocols, could well have its place in prenatal diagnosis, it should, for now, be regarded as an adjunct test not a replacement. The proponents of these tests cite the benefits of speed, accuracy, and reduced cost. Speed is undoubted; accuracy is less easy to defend. Aneuploidy screening can detect nonmosaic trisomies with demonstrable efficiency. These tests, however, do not ever attempt to pick up other clinically important abnormalities routinely encountered during diagnosis, an important shortcoming unless full karyotyping is also undertaken. In addition, the comparative costings provided by Verma and colleagues fail to stand up to scrutiny. They dismiss the biggest component, capital equipment, by suggesting that diagnostic laboratories usually have £93 000 (US$155 000) worth of DNA sequencer lying idle. Figures for return on capital costs, maintenance and other costs should be included. They also base their estimates for consumables only on analysis for trisomy 21. To encompass analysis of other aneuploidies and common unbalanced structural abnormalities, these tests will need additional investment in manpower, equipment, and consumables. Further unspecified and uncosted approaches are necessary for mosaic abnormalities, both real and spurious, and the main difficulty of specimens contaminated by maternal blood. An important point in any comparison is that a cheap alternative with conventional karyotyping is already available. This method involves setting up fewer replicate cultures, processing them earlier, the use of simple staining techniques that do not demonstrate chromosome banding, and the analysis of only very few cells. Inevitably, a percentage of abnormalities would be missed, but it would be a cheaper and faster (although less accurate and effective) technique. In the rush to develop a faster earlier prenatal test for chromosome abnormalities in the mid-1980s, several centres, notably in Holland and Italy, almost abandoned secondtrimester amniocentesis in favour of first-trimester chorionic villus biopsy and direct analysis of cytotrophoblast cells, a decision that was rapidly reversed when the limitations of this approach were appreciated. We should tread carefully to avoid repetition of such mistakes and certainly be participating in a much wider debate about the relative values of aneuploidy screening and conventional karyotyping than has taken place thus far. Prenatal DNA diagnosis of Down's syndrome by PCRAuthors' reply Full-Text PDF