Non-invasive Prenatal Testing Using Fetal DNA
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REVIEW ARTICLE
Non‑invasive Prenatal Testing Using Fetal DNA Giulia Breveglieri1 · Elisabetta D’Aversa1 · Alessia Finotti1,2 · Monica Borgatti1,3
© Springer Nature Switzerland AG 2019
Abstract Non-invasive prenatal diagnosis (NIPD) is based on fetal DNA analysis starting from a simple peripheral blood sample, thus avoiding risks associated with conventional invasive techniques. During pregnancy, the fetal DNA increases to approximately 3–13% of the total circulating free DNA in maternal plasma. The very low amount of circulating cell-free fetal DNA (ccffDNA) in maternal plasma is a crucial issue, and requires specific and optimized techniques for ccffDNA purification from maternal plasma. In addition, highly sensitive detection approaches are required. In recent years, advanced ccffDNA investigation approaches have allowed the application of non-invasive prenatal testing (NIPT) to determine fetal sex, fetal rhesus D (RhD) genotyping, aneuploidies, micro-deletions and the detection of paternally inherited monogenic disorders. Finally, complex and innovative technologies such as digital polymerase chain reaction (dPCR) and next-generation sequencing (NGS) (exhibiting higher sensitivity and/or the capability to read the entire fetal genome from maternal plasma DNA) are expected to allow the detection, in the near future, of maternally inherited mutations that cause genetic diseases. The aim of this review is to introduce the principal ccffDNA characteristics and their applications as the basis of current and novel NIPT.
Key Points
1 Introduction
Cell-free fetal DNA allows non-invasive prenatal testing (NIPT) that carries no risk to the fetus or the mother.
Non-invasive prenatal diagnosis (NIPD) is based on the discovery, in 1997, of circulating cell-free fetal DNA (ccffDNA) within maternal plasma [1] and its aim is to identify genetic abnormalities from the analysis of maternal blood during pregnancy. Currently, first-trimester prenatal diagnosis requires invasive obstetric procedures such as amniocentesis or chorionic villus sampling (CVS), which carry a potential miscarriage risk (with a frequency of approximately 0.5–1%) [2]. The discovery of ccffDNA has facilitated the development of safer and earlier testing procedures based on a simple sampling of maternal blood. Non-invasive prenatal testing (NIPT) has been applied to the determination of fetal sex [3], fetal rhesus D (RhD) genotyping [4], and identification of some pregnancyassociated conditions (such as pre-eclampsia) [5, 6], aneuploidies [7], and paternally inherited monogenic disorders [7–9]. Recently, significant advances have been achieved that would extend the potential applications to fetal whole-genome sequencing and detection of maternally inherited mutations [10–14].
The currently available commercial NIPT kits are able to detect the most common aneuploidies and microdeletions. Novel molecular strategies (such as digital polymerase chain reaction and next-generation sequencing) able to identify single point mutations that cause genetic diso
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