Abstract
Recent advances in molecular genetic technologies have facilitated non-invasive prenatal testing (NIPT) through the analysis of cell-free fetal DNA in maternal plasma. NIPT can be used to identify monogenic disorders including the identification of autosomal recessive disorders where the maternally inherited mutation needs to be identified in the presence of an excess of maternal DNA that contains the same mutation. In the future, simultaneous screening for multiple monogenic disorders is anticipated. Several NIPT methods have been developed to screen for trisomy. These have been shown to be effective for fetal trisomy 21, 18 and 13. Although the testing has been extended to sex chromosome aneuploidy, robust estimates of the efficacy are not yet available and maternal mosaicism for gain or loss of an X-chromosome needs to be considered. Using methods based on the analysis of single nucleotide polymorphisms, diandric triploidy can be identified. NIPT is being developed to identify a number of microdeletion syndromes including α-globin gene deletion. NIPT is a profoundly important development in prenatal care that is substantially advancing the individual patient and public health benefits achieved through conventional prenatal screening and diagnosis.
Highlights
In 1997, Lo et al reported that plasma from pregnant women carrying male fetuses contained cell free DNA derived from the Y-chromosome [1]
The choice of cell free DNA (cf-DNA) testing verses conventional invasive testing may depend on the other skeletal dysplasias that may under consideration in the differential diagnosis because, currently, not all of them will be amenable to a non-invasive diagnosis
The correlation with serum markers probably reflects an underlying correlation with placental volume. This hypothesis would be consistent with a finding that placental volume is smaller [79] and fetal fraction is lower [80] for pregnancies where fetal trisomy 18, trisomy 13, or dygynic triploidy is present
Summary
In 1997, Lo et al reported that plasma from pregnant women carrying male fetuses contained cell free DNA (cf-DNA) derived from the Y-chromosome [1]. This was quickly followed by reports that this cf-DNA could be used for accurately determining fetal sex and Rhesus blood group type [2,3,4]. It is likely that in the USA alone, in excess of 500,000 NIPT studies on women at high risk for fetal aneuploidy were performed in 2013. The testing is widely expected to be extended to women with low a priori risk, additional major chromosome imbalances, sub-microscopic copy number variation, and various monogenic disorders. I review latest developments in this rapidly evolving testing and consider future prospects
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