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A revolutionary new approach for the noninvasive prenatal testing of Down’s syndrome developed by a team led by Professor Dennis Lo Yuk Ming from the Li Ka Shing Institute of Health Sciences of the Faculty of Medicine of The Chinese University of Hong Kong was reported in the latest issue of the top biomedical journal Nature Medicine. This research has been supported by the Innovation and Technology Fund of the Hong Kong SAR Government and the Chair Professorship Scheme of the Li Ka Shing Foundation.

Down’s syndrome testing is a major reason why many pregnant women opt for prenatal testing. Conventional testing for Down’s syndrome involves the use of a combination of ultrasound and blood hormone testing to identify pregnancies that should be recommended for further definitive genetic testing. However, both ultrasound and blood hormone testing do not directly target the central abnormality in Down’s syndrome, namely, the presence of an extra copy of chromosome 21. Due to their indirect nature, these conventional methods of testing have suffered from false-positivity and false-negativity. Consequently, an excess number of otherwise normal pregnancies would be recommended to undergo definitive testing to ensure as many Down’s syndrome fetuses could be detected prenatally. However, conventional definitive genetic testing employs invasive methods, such as amniocentesis to obtain fetal tissue for testing, thus carrying a risk to the fetus. Approximately 40 pregnancies would need to undergo invasive testing for one Down’s syndrome fetus to be detected. Hence, it would be very desirable to develop new tests which would overcome these conventional limitations, namely, tests which target the core abnormality of Down’s syndrome and which are noninvasive.

Professor Lo and his research team discovered, for the first time in the world, the presence of fetal DNA in the blood plasma of pregnant women in 1997. This discovery has opened up new possibility of noninvasive prenatal diagnosis. However, the use of this approach for Down’s syndrome testing has presented a major challenge to many international groups currently working in this field. Professor Lo’s team has now managed to achieve this previously elusive goal by detecting RNA molecules which are copied from a gene located on chromosome 21. Using a novel approach based on the measurement of the ratio of such RNA molecules copied from gene copies which the fetus has inherited from the father and mother, Professor Lo and his team have achieved the noninvasive prenatal detection of Down’s syndrome. In cases which can be analysed by this method, the sensitivity and specificity of the test are 90% and 96.5%, respectively. These figures represent the highest yet reported for a single test. While the current, still experimental test can only be used for a proportion of tested cases, this would already theoretically allow the halving of the number of invasive tests which would be needed for Down’s syndrome testing. It is anticipated that with further refinement, this test will be ready for routine utilization in the next few years.

To summarise, the novel Down’s syndrome testing strategy developed by CUHK has the following advantages:

a. Direct noninvasive detection of fetal Down’s syndrome from a mother’s blood sample
b. As a stand-alone test, can already achieve similar diagnostic accuracy as the conventional strategy that employs multiple testing components
c. Can potentially save some normal pregnancies from the need for invasive genetic testing
d. Unlike the testing of blood hormones, the test profile does not change with the progression of pregnancy. Therefore, a woman can be tested during any time of her pregnancy.
e. Results can be issued in a much shorter timeframe than conventional genetic testing, especially those which are based on fetal cell culture.