Development and Validation of NIPD Trisomy 21 Test

Down syndrome (trisomy 21) is the most common cause of mental impairment or deficiency with an incidence of 1:700 births.  The early detection of trisomy 21 is critical for prospective parents and is an integral component of many national healthcare programs.  Current methods for the prenatal screening and diagnosis of trisomy 21 have limitations.  Prenatal screening tests using sonography and/or measurements of compounds in maternal serum have relatively low sensitivities (~70-90%), very low specificities with high false positive rates and do not provide the most effective prenatal diagnosis.  Even though invasive prenatal diagnostic tests by chorionic villus sampling (CVS), amniocentesis and chordocentesis are accurate and specific, they have other limitations such as a considerable risk for miscarriage (~1-2%) and fetal loss.  Thus, invasive prenatal diagnostic tests can not be applied to all pregnancies and can not provide the most effective prenatal diagnosis.

There is a vital need to develop a Non-Invasive Prenatal Diagnostic (NIPD) test that can be offered to all pregnancies, does not put the fetus at risk for miscarriage and provides a more effective prenatal diagnosis for Down syndrome and other genetic disorders.  The development of such a test is widely anticipated by prospective parents, health care providers and the scientific community.  Several groups have been working towards this goal for the past fifteen years.  However, the development of a NIPD test has been a great challenge due to the limited amount of free fetal DNA (ffDNA) (3-5%) in maternal circulation.

NIPD Genetics has been successful in developing a NIPD test for the diagnosis of trisomy 21 during the early stages of pregnancy (as early as the 10th week of gestation).  The results of this study have been published earlier this year in the prestigious journal, Nature Medicine (details are available in our Publications section).  Our Non-Invasive Prenatal Diagnostic test for trisomy 21 is based on the identification of differentially methylated fetal-specific markers and the use of those Differentially Methylated Regions (DMRs) for the discrimination between a trisomy 21 fetus and a normal fetus by real-time quantitative PCR (see graph for example).  By assaying multiple DMRs across chromosome 21 we were able to achieve 100% sensitivity and 100% specificity.

The application of this novel test is sensitive, specific, safe, simple, affordable and does not require specialized or complex laboratory equipment, software or know-how.  Results can be obtained within 3 days and the cost is lower than that of current invasive methods.  Therefore, the test is suitable for routine laboratory procedures and can be readily introduced by any genetic diagnostic laboratory.